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Parkinson’s disease is not one, but two diseases

https://www.sciencedaily.com/releases/2020/09/200922092156.htm

Parkinson’s disease is not one, but two diseases
Date:
September 22, 2020
Source:
Aarhus University
Summary:
Researchers around the world have been puzzled by the different symptoms and varied disease pathways of Parkinson’s patients. A major study has now identified that there are actually two types of the disease.

Asparagine endopeptidase inhibitor protects against fenpropathrin-induced neurodegeneration via suppressing α-synuclein aggregation and neuroinflammation

https://www.sciencedirect.com/science/article/abs/pii/S0014299920306786?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/32971086?dopt=Abstract

TITLE:
Asparagine endopeptidase inhibitor protects against fenpropathrin-induced neurodegeneration via suppressing α-synuclein aggregation and neuroinflammation.

DESCRIPTION:
Asparagine endopeptidase inhibitor protects against fenpropathrin-induced neurodegeneration via suppressing α-synuclein aggregation and neuroinflammation.

Eur J Pharmacol. 2020 Sep 21;:173586

Authors: Yu T, Wan F, Liu C, Zhang X, Liu Z, Zhang J, Xiong J, Wang T, Zhang Z

Abstract

Exposure to fenpropathrin (Fen), one of the most widely used pyrethroid pesticides, has been reported to increase the incidence of Parkinson’s disease (PD). However, the molecular mechanisms underlying Fen-induced Parkinsonism remain unknown. Here we investigated the role of the lysosomal protease asparagine endopeptidase (AEP) in Fen-induced neurodegeneration and tested the protective effect of an AEP inhibitor Compound #11 (CP11). Fen induced AEP activation, α-synuclein aggregation, and dopaminergic neuronal degeneration both in vitro and in vivo. CP11 alleviated Fen-induced cell injury in cultured SH-SY5Y cells and A53T α-synuclein transgenic mice. CP11 protected SH-SY5Y cells against Fen-induced toxicity and decreased α-synuclein aggregation in HEK293 cells stably transfected with α-synuclein. In Fen-treated mice, CP11 attenuated the degeneration of dopaminergic neurons and reduced neuroinflammation. Our findings demonstrate that neurodegeneration in Fen-treated models might be attributed to the activation of AEP. AEP might be a novel therapeutic target in PD induced by Fen and other environmental factors.

PMID: 32971086 [PubMed – as supplied by publisher]

PMID:
PubMed:32971086

DATE FOUND:
09/25/20 06:01AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32971086?dopt=Abstract

A Clinical Study of NLY01 in Patient’s With Early Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT04154072?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=10%2F23%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Clinical Study of NLY01 in Patient’s With Early Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: NLY01;   Drug: Vehicle
Sponsor:   Neuraly, Inc.
Not yet recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT04154072

FIRST POSTED:
Wed, 06 Nov 2019 12:00:00 EST

LAST UPDATE POSTED:
11/06/19 08:26AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT04154072?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=10%2F23%2F2019&lupd_d=14&sort=nwst

Gene Therapy in the Management of Parkinson’s Disease: Potential of GDNF as a Promising Therapeutic Strategy

https://www.eurekaselect.com/184936/article

https://www.ncbi.nlm.nih.gov/pubmed/32811394?dopt=Abstract

TITLE:
Gene Therapy in the Management of Parkinson’s Disease: Potential of GDNF as a Promising Therapeutic Strategy.

DESCRIPTION:
Related Articles

Gene Therapy in the Management of Parkinson’s Disease: Potential of GDNF as a Promising Therapeutic Strategy.

Curr Gene Ther. 2020 Aug 17;:

Authors: Behl T, Kaur I, Kumar A, Mehta V, Zengin G, Arora S

Abstract

The limitations of conventional treatment therapies in Parkinson’s disorder, a common neurodegenerative disorder, lead to the development of an alternative gene therapy approach. Multiple treatment options targeting dopaminergic neuronal regeneration, production of enzymes linked with dopamine synthesis, subthalamic nucleus neurons, regulation of astrocytes and microglial cells and potentiating neurotrophic factors, were established. Viral vector-based dopamine delivery, prodrug approaches, fetal ventral mesencephalon tissue transplantation and dopamine synthesizing enzyme encoding gene delivery are significant therapies evidently supported by numerous trials. The review primarily elaborates the significant role of glial cell-line derived neurotrophic factor in alleviating motor symptoms and loss of dopaminergic neurons in Parkinson’s disease. Neuroprotective and neuroregenerative effects of GDNF were established via preclinical and clinical study outcomes. The binding of GDNF family ligands with associated receptors lead to the formation of a receptor-ligand complex activating Ret receptor of tyrosine kinase family, which is only expressed in dopaminergic neurons, playing an important role in Parkinson’s disease, via its association with essential protein encoded genes. Furthermore, the review establishes delivery aspects, like ventricular delivery of recombinant GDNF, intraparenchymal and intraputaminal delivery using infusion catheters. The review highlights problems and challenges of GDNF delivery, and essential measures to overcome them, like gene therapy combinations, optimization of delivery vectors, newer targeting devices, motor symptoms curbing focused ultrasound techniques, modifications in patient selection criteria and development of novel delivery strategies based on liposomes and encapsulated cells, to promote safe and effective delivery of neurotrophic factor and establishment of a routine treatment therapy for patients.

PMID: 32811394 [PubMed – as supplied by publisher]

PMID:
PubMed:32811394

DATE FOUND:
08/20/20 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32811394?dopt=Abstract

Microbiota Intervention to Change the Response of Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03575195?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=07%2F31%2F2020&lupd_d=14&sort=nwst

STUDY TITLE:
Microbiota Intervention to Change the Response of Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: Rifaximin;   Other: Placebo
Sponsors:   University of California, San Francisco;   Nova Southeastern University;   Gateway Institute for Brain Research
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03575195

FIRST POSTED:
Mon, 02 Jul 2018 12:00:00 EDT

LAST UPDATE POSTED:
08/14/20 07:39AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03575195?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=07%2F31%2F2020&lupd_d=14&sort=nwst

A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB094 in Adults With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03976349?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F23%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB094 in Adults With Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson’s Disease
Interventions:   Drug: BIIB094;   Drug: Placebo
Sponsors:   Biogen;   Ionis Pharmaceuticals, Inc.
Not yet recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03976349

FIRST POSTED:
Thu, 06 Jun 2019 12:00:00 EDT

LAST UPDATE POSTED:
06/06/19 07:37AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03976349?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F23%2F2019&lupd_d=14&sort=nwst

Recent developments in the treatment of Parkinson’s Disease

https://f1000research.com/articles/9-862/v1

https://www.ncbi.nlm.nih.gov/pubmed/32789002?dopt=Abstract

TITLE:
Recent developments in the treatment of Parkinson’s Disease.

DESCRIPTION:
Recent developments in the treatment of Parkinson’s Disease.

F1000Res. 2020;9:

Authors: Stoker TB, Barker RA

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease typified by a movement disorder consisting of bradykinesia, rest tremor, rigidity, and postural instability. Treatment options for PD are limited, with most of the current approaches based on restoration of dopaminergic tone in the striatum. However, these do not alter disease course and do not treat the non-dopamine-dependent features of PD such as freezing of gait, cognitive impairment, and other non-motor features of the disorder, which often have the greatest impact on quality of life. As understanding of PD pathogenesis grows, novel therapeutic avenues are emerging. These include treatments that aim to control the symptoms of PD without the problematic side effects seen with currently available treatments and those that are aimed towards slowing pathology, reducing neuronal loss, and attenuating disease course. In this latter regard, there has been much interest in drug repurposing (the use of established drugs for a new indication), with many drugs being reported to affect PD-relevant intracellular processes. This approach offers an expedited route to the clinic, given that pharmacokinetic and safety data are potentially already available. In terms of better symptomatic therapies that are also regenerative, gene therapies and cell-based treatments are beginning to enter clinical trials, and developments in other neurosurgical strategies such as more nuanced deep brain stimulation approaches mean that the landscape of PD treatment is likely to evolve considerably over the coming years. In this review, we provide an overview of the novel therapeutic approaches that are close to, or are already in, clinical trials.

PMID: 32789002 [PubMed – as supplied by publisher]

PMID:
PubMed:32789002

DATE FOUND:
08/14/20 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32789002?dopt=Abstract

Neuroprotective and neurogenic effects of novel tetramethylpyrazine derivative T-006 in Parkinson’s disease models through activating the MEF2-PGC1α and BDNF/CREB pathways

https://www.aging-us.com/article/103551

https://www.ncbi.nlm.nih.gov/pubmed/32710729?dopt=Abstract

TITLE:
Neuroprotective and neurogenic effects of novel tetramethylpyrazine derivative T-006 in Parkinson’s disease models through activating the MEF2-PGC1α and BDNF/CREB pathways.

DESCRIPTION:
Related Articles

Neuroprotective and neurogenic effects of novel tetramethylpyrazine derivative T-006 in Parkinson’s disease models through activating the MEF2-PGC1α and BDNF/CREB pathways.

Aging (Albany NY). 2020 Jul 24;12:

Authors: Chen H, Cao J, Zha L, Wang P, Liu Z, Guo B, Zhang G, Sun Y, Zhang Z, Wang Y

Abstract

T-006, a new derivative of tetramethylpyrazine, has been recently found to protect against 6-hydroxydopamine (6-OHDA)-induced neuronal damage and clear α-synuclein (α-syn) by enhancing proteasome activity in an α-syn transgenic Parkinson’s disease (PD) model. The effect of T-006 on the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model, however, has not been tested and T-006’s neuroprotective mechanisms have not been fully elucidated. In this study, we further investigated the neuroprotective and neurogenic effects of T-006 and explored its underlying mechanism of action in both cellular and animal PD models. T-006 was able to improve locomotor behavior, increase survival of nigra dopaminergic neurons and boost striatal dopamine levels in both MPTP- and 6-OHDA-induced animals. T-006 treatment restored the altered expressions of myocyte enhancer factor 2D (MEF2D), peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1α (PGC1α) and NF-E2-related factor 1/2 (Nrf1/2) via modulation of Akt/GSK3β signaling. T-006 stimulated MEF2, PGC1α and Nrf2 transcriptional activities, inducing Nrf2 nuclear localization. Interestingly, T-006 promoted endogenous adult neurogenesis toward a dopaminergic phenotype by activating brain-derived neurotrophic factor (BDNF) and cAMP responsive element-binding protein (CREB) in 6-OHDA rats. Our work demonstrated that T-006 is a potent neuroprotective and neuroregenerative agent that may have therapeutic potential in the treatment of PD.

PMID: 32710729 [PubMed – as supplied by publisher]

PMID:
PubMed:32710729

DATE FOUND:
07/28/20 06:01AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32710729?dopt=Abstract

Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03318523?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F15%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Participants With Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson’s Disease
Interventions:   Drug: Placebo;   Drug: BIIB054
Sponsor:   Biogen
Active, not recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03318523

FIRST POSTED:
Tue, 24 Oct 2017 12:00:00 EDT

LAST UPDATE POSTED:
05/29/19 07:29AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03318523?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F15%2F2019&lupd_d=14&sort=nwst

Identifying and predicting Parkinson’s disease subtypes through trajectory clustering via bipartite networks

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233296

https://www.ncbi.nlm.nih.gov/pubmed/32555729?dopt=Abstract

TITLE:
Identifying and predicting Parkinson’s disease subtypes through trajectory clustering via bipartite networks.

DESCRIPTION:
Identifying and predicting Parkinson’s disease subtypes through trajectory clustering via bipartite networks.

PLoS One. 2020;15(6):e0233296

Authors: Krishnagopal S, Coelln RV, Shulman LM, Girvan M

Abstract

Chronic medical conditions show substantial heterogeneity in their clinical features and progression. We develop the novel data-driven, network-based Trajectory Profile Clustering (TPC) algorithm for 1) identification of disease subtypes and 2) early prediction of subtype/disease progression patterns. TPC is an easily generalizable method that identifies subtypes by clustering patients with similar disease trajectory profiles, based not only on Parkinson’s Disease (PD) variable severity, but also on their complex patterns of evolution. TPC is derived from bipartite networks that connect patients to disease variables. Applying our TPC algorithm to a PD clinical dataset, we identify 3 distinct subtypes/patient clusters, each with a characteristic progression profile. We show that TPC predicts the patient’s disease subtype 4 years in advance with 72% accuracy for a longitudinal test cohort. Furthermore, we demonstrate that other types of data such as genetic data can be integrated seamlessly in the TPC algorithm. In summary, using PD as an example, we present an effective method for subtype identification in multidimensional longitudinal datasets, and early prediction of subtypes in individual patients.

PMID: 32555729 [PubMed – in process]

PMID:
PubMed:32555729

DATE FOUND:
06/20/20 06:00AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32555729?dopt=Abstract

Solving a Parkinson’s disease puzzle through protein design: breakthrough will open up a new dimension in drug discovery for Parkinson’s disease

https://www.sciencedaily.com/releases/2020/06/200611094114.htm

Solving a Parkinson’s disease puzzle through protein design
Date:
June 11, 2020
Source:
Ecole Polytechnique Fédérale de Lausanne
Summary:
Scientists have developed a computational protein design approach, and used it to obtain the first ever high-resolution structure of an activated dopamine receptor in its natural cell membrane environment. The breakthrough will open up a new dimension in drug discovery for Parkinson’s disease and perhaps other disorders.

Discovery and optimization of 3-thiophenylcoumarins as novel agents against Parkinson’s disease

https://www.sciencedirect.com/science/article/abs/pii/S0045206820312839?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/32569895?dopt=Abstract

TITLE:
Discovery and optimization of 3-thiophenylcoumarins as novel agents against Parkinson’s disease: Synthesis, in vitro and in vivo studies.

DESCRIPTION:
Discovery and optimization of 3-thiophenylcoumarins as novel agents against Parkinson’s disease: Synthesis, in vitro and in vivo studies.

Bioorg Chem. 2020 Jun 02;101:103986

Authors: Rodríguez-Enríquez F, Viña D, Uriarte E, Fontenla JA, Matos MJ

Abstract

Monoamine oxidase B (MAO-B) inhibitors are still receiving great attention as promising therapeutic agents for central nervous system disorders. This study explores, for the first time, the potential of 3-thiophenylcoumarins as in vitro and in vivo agents against Parkinsońs disease. Twelve compounds were synthesized via Perkin-Oglialoro reaction, and in vitro evaluation of six hydroxylated molecules was performed. MAO-A and MAO-B inhibition, DPPH scavenging and inhibition of ROS formation, neurotoxicity on motor cortex neurons and neuroprotection against H2O2, were studied. In vivo effect on locomotor activity using the open field test was also evaluated for the best candidate [3-(4′-bromothiophen-2′-yl)-7-hydroxycoumarin, 5], a potent, selective and reversible MAO-B inhibitor (IC50 = 140 nM). This compound proved to have a slightly better in vivo profile than selegiline, one of the currently treatments for Parkinson’s disease, in reserpinized mice pretreated with levodopa and benserazide. Results suggested that, comparing positions 7 and 8, substitution at position 7 of the coumarin scaffold is better for the enzymatic inhibition. However, the presence of a catechol at positions 7 and 8 exponentially increases the antioxidant potential and the neuroprotective properties. Finally, all the molecules present good theoretical physicochemical properties that make them excellent candidates for the optimization of a lead compound.

PMID: 32569895 [PubMed – as supplied by publisher]

PMID:
PubMed:32569895

DATE FOUND:
06/23/20 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32569895?dopt=Abstract

Simvastatin as a Neuroprotective Treatment for Moderate Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT02787590?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F18%2F2020&lupd_d=14&sort=nwst

STUDY TITLE:
Simvastatin as a Neuroprotective Treatment for Moderate Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: Simvastatin;   Drug: Matched Placebo (for Simvastatin)
Sponsors:   University Hospital Plymouth NHS Trust;   University of Plymouth
Active, not recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT02787590

FIRST POSTED:
Wed, 01 Jun 2016 12:00:00 EDT

LAST UPDATE POSTED:
06/01/20 07:10AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT02787590?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F18%2F2020&lupd_d=14&sort=nwst

Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases such as Parkinson’s disease

https://www.frontiersin.org/articles/10.3389/fphys.2020.00361/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199656/

https://www.ncbi.nlm.nih.gov/pubmed/32411012?dopt=Abstract

TITLE:
Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases.

DESCRIPTION:
Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases.

Front Physiol. 2020;11:361

Authors: Momtaz S, Memariani Z, El-Senduny FF, Sanadgol N, Golab F, Katebi M, Abdolghaffari AH, Farzaei MH, Abdollahi M

Abstract

Misfolded proteins are the main common feature of neurodegenerative diseases, thereby, normal proteostasis is an important mechanism to regulate the neural survival and the central nervous system functionality. The ubiquitin-proteasome system (UPS) is a non-lysosomal proteolytic pathway involved in numerous normal functions of the nervous system, modulation of neurotransmitter release, synaptic plasticity, and recycling of membrane receptors or degradation of damaged and regulatory intracellular proteins. Aberrant accumulation of intracellular ubiquitin-positive inclusions has been implicated to a variety of neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Myeloma (MM). Genetic mutation in deubiquitinating enzyme could disrupt UPS and results in destructive effects on neuron survival. To date, various agents were characterized with proteasome-inhibitory potential. Proteins of the ubiquitin-proteasome system, and in particular, E3 ubiquitin ligases, may be promising molecular targets for neurodegenerative drug discovery. Phytochemicals, specifically polyphenols (PPs), were reported to act as proteasome-inhibitors or may modulate the proteasome activity. PPs modify the UPS by means of accumulation of ubiquitinated proteins, suppression of neuronal apoptosis, reduction of neurotoxicity, and improvement of synaptic plasticity and transmission. This is the first comprehensive review on the effect of PPs on UPS. Here, we review the recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders. This review attempts to summarize the latest reports on the neuroprotective properties involved in the proper functioning of natural polyphenolic compounds with implication for targeting ubiquitin-proteasome pathway in the neurodegenerative diseases. We highlight the evidence suggesting that polyphenolic compounds have a dose and disorder dependent effects in improving neurological dysfunctions, and so their mechanism of action could stimulate the UPS, induce the protein degradation or inhibit UPS and reduce protein degradation. Future studies should focus on molecular mechanisms by which PPs can interfere this complex regulatory system at specific stages of the disease development and progression.

PMID: 32411012 [PubMed]

PMID:
PubMed:32411012

DATE FOUND:
05/16/20 06:01AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32411012?dopt=Abstract

TSPO-PET for Neuroinflammation in Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03457493?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=04%2F13%2F2020&lupd_d=14&sort=nwst

STUDY TITLE:
TSPO-PET for Neuroinflammation in Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Intervention:   Drug: DPA-714-PET/MRI
Sponsor:   University of Alabama at Birmingham
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03457493

FIRST POSTED:
Wed, 07 Mar 2018 12:00:00 EST

LAST UPDATE POSTED:
04/27/20 09:21AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03457493?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=04%2F13%2F2020&lupd_d=14&sort=nwst

A Phase 3 Study With P2B001 in Subjects With Early Parkinson’s

https://clinicaltrials.gov/ct2/show/NCT03329508?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=08%2F15%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Phase 3 Study With P2B001 in Subjects With Early Parkinson’s

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: P2B001;   Drug: Rasagiline;   Drug: Pramipexole;   Drug: Pramipexole ER
Sponsor:   Pharma Two B Ltd.
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03329508

FIRST POSTED:
Mon, 06 Nov 2017 12:00:00 EST

LAST UPDATE POSTED:
08/29/19 10:25AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03329508?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=08%2F15%2F2019&lupd_d=14&sort=nwst

Effect of Melatonin Administration on the PER1 and BMAL1 Clock Genes in Patients With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT04287543?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=02%2F13%2F2020&lupd_d=14&sort=nwst

STUDY TITLE:
Melatonin on Clock Genes in Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: Melatonin;   Drug: Placebos
Sponsor:   Instituto Mexicano del Seguro Social
Enrolling by invitation

CLINICALTRIALS.GOV IDENTIFIER:
NCT04287543

FIRST POSTED:
Thu, 27 Feb 2020 12:00:00 EST

LAST UPDATE POSTED:
02/27/20 09:09AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT04287543?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=02%2F13%2F2020&lupd_d=14&sort=nwst

Glucocerebrosidase as a Therapeutic Target for Parkinson’s Disease

https://www.tandfonline.com/doi/abs/10.1080/14728222.2020.1733970?journalCode=iett20

https://www.ncbi.nlm.nih.gov/pubmed/32106725?dopt=Abstract

TITLE:
Glucocerebrosidase as a therapeutic target for Parkinson’s disease.

DESCRIPTION:
Related Articles

Glucocerebrosidase as a therapeutic target for Parkinson’s disease.

Expert Opin Ther Targets. 2020 Feb 27;:1-8

Authors: Chen Y, Sam R, Sharma P, Chen L, Do J, Sidransky E

Abstract

Introduction: The association between Gaucher disease, caused by the inherited deficiency of glucocerebrosidase, and Parkinson’s disease was first recognized in the clinic, noting that patients with Gaucher disease and their carrier relatives had an increased incidence of Parkinson’s disease. Currently, mutations in glucocerebrosidase (GBA1) are the most common genetic risk factor for Parkinson’s disease and dementia with Lewy bodies, with an inverse relationship between glucocerebrosidase and α-synuclein, a key factor in Parkinson pathogenesis. The hypothesis that therapeutic enhancement of brain glucocerebrosidase levels might reduce the aggregation, accumulation or spread of α-synuclein has spurred great interest in glucocerebrosidase as a novel therapeutic target.Area covered: This article explores the potential molecular mechanisms underlying the association between GBA1 mutations and Parkinson’s disease and outlines therapeutic strategies to increase brain glucocerebrosidase, including gene therapy, targeted delivery of recombinant glucocerebrosidase to the brain, small-molecule chaperones to rescue mutant glucocerebrosidase, and small-molecule modulators to activate wild-type glucocerebrosidase.Expert opinion: Although an improved understanding of the mechanistic basis for GBA1-associated parkinsonism is essential, enhancing levels of brain glucocerebrosidase may have wide therapeutic implications. While gene therapy may ultimately be effective, less expensive and invasive small-molecule non-inhibitory chaperones or activators could significantly impact the disease course.

PMID: 32106725 [PubMed – as supplied by publisher]

PMID:
PubMed:32106725

DATE FOUND:
02/29/20 06:01AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32106725?dopt=Abstract

Molecule BT13 offers hope for halting Parkinson’s: has potential to boost dopamine levels and protect dopamine-producing brain cells from dying

https://www.sciencedaily.com/releases/2020/02/200214183216.htm

Molecule offers hope for halting Parkinson’s

Date:
February 14, 2020

Source:
Parkinson’s UK

Summary:
A promising molecule has offered hope for a new treatment that could stop or slow Parkinson’s, something no treatment can currently do.

A promising molecule has offered hope for a new treatment that could stop or slow Parkinson’s, something no treatment can currently do.

Researchers from the University of Helsinki found that molecule BT13 has the potential to both boost levels of dopamine, the chemical that is lost in Parkinson’s, as well as protect the dopamine-producing brain cells from dying.

San Diego biotech uses advanced stem cell techniques in hopes of rolling back the clock on Parkinson’s symptoms

https://www.sandiegouniontribune.com/business/biotech/story/2019-12-13/aspen-neuroscience-raises-funds-to-pursue-personalized-cell-therapy-for-parkinsons-disease

Aspen Neuroscience gets funding to pursue personalized cell therapy for Parkinson’s disease

San Diego biotech uses advanced stem cell techniques in hopes of rolling back the clock on Parkinson’s symptoms
By MIKE FREEMAN
DEC. 13, 2019 6 AM

Neuroprotective effects of Bacopa monnieri in Parkinson’s disease model

https://link.springer.com/article/10.1007%2Fs11011-019-00526-w

https://www.ncbi.nlm.nih.gov/pubmed/31834548?dopt=Abstract

TITLE:
Neuroprotective effects of Bacopa monnieri in Parkinson’s disease model.

DESCRIPTION:
Neuroprotective effects of Bacopa monnieri in Parkinson’s disease model.

Metab Brain Dis. 2019 Dec 13;:

Authors: Singh B, Pandey S, Rumman M, Mahdi AA

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra region and the presence of α-synuclein aggregates in the striatum and surrounding areas of brain. Evidences suggest that neuroinflammation plays a role in the progression of PD. We examined the neuro-protective effects of Bacopa monnieri (BM) in regulating neuroinflammation. Administration of BM suppressed the level of pro-inflammatory cytokines, decreased the levels of α-synuclein, and reduced reactive oxygen species (ROS) generation in PD animal model. Pre-treatment of BM showed more prominent results as compare to co- and post-treatment. Results suggest that Bacopa can limit inflammation in the different areas of brain, thus, offers a promising source of novel therapeutics for the treatment of many CNS disorders.

PMID: 31834548 [PubMed – as supplied by publisher]

PMID:
PubMed:31834548

DATE FOUND:
12/14/19 06:02AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31834548?dopt=Abstract

Blocking CXCL12/CXCR4 may be a potential therapeutic approach for Parkinson’s disease progression

https://www.ncbi.nlm.nih.gov/pubmed/31831012?dopt=Abstract

TITLE:
CXCL12 is involved in α-synuclein-triggered neuroinflammation of Parkinson’s disease.

DESCRIPTION:
Related Articles

CXCL12 is involved in α-synuclein-triggered neuroinflammation of Parkinson’s disease.

J Neuroinflammation. 2019 Dec 12;16(1):263

Authors: Li Y, Niu M, Zhao A, Kang W, Chen Z, Luo N, Zhou L, Zhu X, Lu L, Liu J

Abstract

BACKGROUND: The mechanisms underlying the pathogenesis and progression of Parkinson’s disease (PD) remain elusive, but recent opinions and perspectives have focused on whether the inflammation process induced by microglia contributes to α-synuclein-mediated toxicity. Migration of microglia to the substantia nigra (SN) could precede neurodegeneration in A53T mice. We hypothesized that CXCL12 could be a mediator in the α-synuclein-induced migration of microglia.

METHODS: After establishing appropriate animal and cell culture models, we explored the relationship between α-synuclein and CXCL12 in A53T mice, primary microglia, and BV-2 cell lines. We also explored the mechanisms of these interactions and the signaling processes involved in neuroinflammation.

RESULTS: We confirmed the positive correlation between α-synuclein and CXCL12 in the postmortem brain tissue of PD patients and the upregulated CXCR4 expression in SN microglia of A53T mice. In addition, as expected, α-synuclein increased the production of CXCL12 in microglia via TLR4/IκB-α/NF-κB signaling. Importantly, CXCL12/CXCR4/FAK/Src/Rac1 signaling was shown to be involved in α-synuclein-induced microglial accumulation.

CONCLUSIONS: Our study suggests that CXCL12 could be a novel target for the prevention of α-synuclein-triggered ongoing microglial responses. Blocking CXCL12/CXCR4 may be a potential therapeutic approach for PD progression.

PMID: 31831012 [PubMed – in process]

PMID:
PubMed:31831012

DATE FOUND:
12/14/19 06:02AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31831012?dopt=Abstract

Fecal transplantation to treat patients with Parkinson’s disease: Hope or hype?

https://www.eurekalert.org/pub_releases/2019-11/ip-ftt111519.php

Fecal transplantation to treat patients with Parkinson’s disease: Hope or hype?

Scientists review the evidence for using fecal transplantation and pre- and probiotics in patients with Parkinson’s disease in the Journal of Parkinson’s Disease

Targeting the microglial NLRP3 inflammasome and its role in Parkinson’s disease

https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27874

https://www.ncbi.nlm.nih.gov/pubmed/31680318?dopt=Abstract

TITLE:
Targeting the microglial NLRP3 inflammasome and its role in Parkinson’s disease.

DESCRIPTION:
Related Articles

Targeting the microglial NLRP3 inflammasome and its role in Parkinson’s disease.

Mov Disord. 2019 Nov 04;:

Authors: Haque ME, Akther M, Jakaria M, Kim IS, Azam S, Choi DK

Abstract

Excessive activation of microglia and subsequent release of proinflammatory cytokines play a crucial role in neuroinflammation and neurodegeneration in Parkinson’s disease (PD). Components of the nucleotide-binding oligomerization domain and leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome complex, leucine-rich-repeat- and pyrin-domain-containing 3, caspase-1, and apoptosis-associated speck-like protein containing a CARD, are highly expressed in activated microglia in PD patient brains. Findings suggest that neurotoxins, aggregation of α-synuclein, mitochondrial reactive oxygen species, and disrupted mitophagy are the key regulators of microglial leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome activation and release of interleukin-1β and interleukin-18 caspase-1-mediated pyroptotic cell death in the substantia nigra of the brain. Although this evidence suggests the leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome may be a potential drug target for treatment of PD, the exact mechanism of how the microglia sense these stimuli and initiate leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome signaling is unknown. Here, the molecular mechanism and regulation of microglial leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome activation and its role in the pathogenesis of PD are discussed. Moreover, the potential of both endogenous and synthetic leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome modulators, long noncoding RNA, microRNA to develop novel therapeutics to treat PD is presented. Overall, we recommend that the microglial leucine-rich-repeat- and pyrin-domain-containing 3 inflammasome can be a potential target for PD treatment. © 2019 International Parkinson and Movement Disorder Society.

PMID: 31680318 [PubMed – as supplied by publisher]

PMID:
PubMed:31680318

DATE FOUND:
11/05/19 06:00AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31680318?dopt=Abstract

Systemic activation of Nrf2 pathway in Parkinson’s disease

https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27878

https://www.ncbi.nlm.nih.gov/pubmed/31682033?dopt=Abstract

TITLE:
Systemic activation of Nrf2 pathway in Parkinson’s disease.

DESCRIPTION:
Systemic activation of Nrf2 pathway in Parkinson’s disease.

Mov Disord. 2019 Nov 04;:

Authors: Petrillo S, Schirinzi T, Di Lazzaro G, D’Amico J, Colona VL, Bertini E, Pierantozzi M, Mari L, Mercuri NB, Piemonte F, Pisani A

Abstract

BACKGROUND: Preclinical studies underlined the relevance of Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor pathway in the pathogenesis of Parkinson’s disease (PD).

OBJECTIVE: The objective of this study was to explore Nrf2 pathway in vivo in PD, looking for novel disease biomarkers and therapeutic targets.

METHODS: The levels of Nrf2, the downstream effectors (NAD(P)H dehydrogenase [quinone] 1 (Nqo1) enzyme, glutathione metabolism enzymes Glutamate-cysteine ligase (GCL) and Glutathione Reductase (GR)), the upstream activators (redox state and mitochondrial dysfunction), and α-synuclein oligomers were assessed in the blood leukocytes of PD patients comparatively to controls. Biochemical data were correlated to clinical parameters.

RESULTS: In PD, Nrf2 was highly transcribed and expressed as well as its target effectors. The mitochondrial complex I activity was reduced and the oxidized form of glutathione prevailed, disclosing the presence of pathway’s activators. Also, α-synuclein oligomers levels were increased. Nrf2 transcript and oligomers levels correlated with PD duration.

CONCLUSIONS: Blood leukocytes mirror pathogenic mechanisms of PD, showing the systemic activation of the Nrf2 pathway and its link with synucleinopathy and clinical events. © 2019 International Parkinson and Movement Disorder Society.

PMID: 31682033 [PubMed – as supplied by publisher]

PMID:
PubMed:31682033

DATE FOUND:
11/05/19 06:05AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31682033?dopt=Abstract

Brain Bioenergetics in Parkinson’s Disease and Response to Repeated Oral UDCA Treatment

https://clinicaltrials.gov/ct2/show/NCT02967250?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=10%2F18%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Brain Bioenergetics in Parkinson’s Disease and Response to Repeated Oral UDCA Treatment

DESCRIPTION:
Condition:   Parkinson Disease
Intervention:   Drug: ursodeoxycholic acid
Sponsor:   University of Minnesota
Not yet recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT02967250

FIRST POSTED:
Fri, 18 Nov 2016 12:00:00 EST

LAST UPDATE POSTED:
11/01/19 08:39AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT02967250?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=10%2F18%2F2019&lupd_d=14&sort=nwst

A Study to Evaluate NYX-458 in Subjects With Mild Cognitive Impairment Associated With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT04148391?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=10%2F18%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Evaluate NYX-458 in Subjects With MCI-PD

DESCRIPTION:
Conditions:   Parkinson’s Disease;   Mild Cognitive Impairment
Interventions:   Drug: Placebo Oral Capsule;   Drug: NYX-458
Sponsors:   Aptinyx;   CogState Ltd.;   Worldwide Clinical Trials
Not yet recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT04148391

FIRST POSTED:
Fri, 01 Nov 2019 12:00:00 EDT

LAST UPDATE POSTED:
11/01/19 07:39AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT04148391?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=10%2F18%2F2019&lupd_d=14&sort=nwst

Editorial: Peripheral Immunity in Parkinson’s Disease: Emerging Role and Novel Target for Therapeutics

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804273/

https://www.ncbi.nlm.nih.gov/pubmed/31681151?dopt=Abstract

TITLE:
Editorial: Peripheral Immunity in Parkinson’s Disease: Emerging Role and Novel Target for Therapeutics.

DESCRIPTION:
Related Articles

Editorial: Peripheral Immunity in Parkinson’s Disease: Emerging Role and Novel Target for Therapeutics.

Front Neurol. 2019;10:1080

Authors: Comi C, Cosentino M, Pacheco R

PMID: 31681151 [PubMed]

PMID:
PubMed:31681151

DATE FOUND:
11/05/19 07:43AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31681151?dopt=Abstract

Scientists find potential diagnostic tool, treatment for Parkinson’s disease

http://med.stanford.edu/news/all-news/2019/09/scientists-find-potential-diagnostic-tool-treatment.html

Scientists find potential diagnostic tool, treatment for Parkinson’s disease
In human cell cultures, countering a defect that appears to be nearly universal among patients with Parkinson’s disease prevents death in the cells whose loss causes the disease.

Transplantation of Neural Stem Cell-Derived Neurons for Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03309514?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=09%2F12%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Transplantation of Neural Stem Cell-Derived Neurons for Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson’s Disease
Intervention:   Biological: Intracerebral microinjections
Sponsor:   NeuroGeneration
Not yet recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03309514

FIRST POSTED:
Fri, 13 Oct 2017 12:00:00 EDT

LAST UPDATE POSTED:
09/26/19 07:45AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03309514?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=09%2F12%2F2019&lupd_d=14&sort=nwst

Study to Evaluate APL-130277 in Subjects With Parkinson’s Disease Complicated by Motor Fluctuations

https://clinicaltrials.gov/ct2/show/NCT03391882?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F01%2F2019&lupd_d=14&sort=nwst

Study to Evaluate APL-130277 in Subjects With Parkinson’s Disease Complicated by Motor Fluctuations

Study
STUDY TITLE:
A Study of an Investigational Drug to See How it Affects the People With Parkinson’s Disease Complicated by Motor Fluctuations (“OFF” Episodes) Compared to an Approved Drug Used to Treat People With Parkinson’s Disease Complicated by Motor Fluctuations (“OFF” Episodes)

DESCRIPTION:
Condition:   Motor OFF Episodes Associated With Parkinson’s Disease
Interventions:   Drug: APL-130277;   Drug: subcutaneous apomorphine
Sponsor:   Sunovion
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03391882

FIRST POSTED:
Fri, 05 Jan 2018 12:00:00 EST

LAST UPDATE POSTED:
05/15/19 07:32AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03391882?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F01%2F2019&lupd_d=14&sort=nwst

Targeting BDNF signaling by natural products: novel synaptic repair therapeutics for neurodegeneration and behavior disorders

https://www.sciencedirect.com/science/article/abs/pii/S1043661819318225?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31546015?dopt=Abstract

TITLE:
Targeting BDNF signaling by natural products: novel synaptic repair therapeutics for neurodegeneration and behavior disorders.

DESCRIPTION:
Targeting BDNF signaling by natural products: novel synaptic repair therapeutics for neurodegeneration and behavior disorders.

Pharmacol Res. 2019 Sep 20;:104458

Authors: Bawari S, Tewari D, Argüelles S, Sah AN, Fazel Nabavi S, Xu S, Vacca RA, Nabavi SM, Shirooie S

Abstract

Neurodegenerative disorders like Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, spinocerebellar ataxias, amyotrophic lateral sclerosis, frontotemporal dementia to prion diseases, Friedreich’s ataxia, hereditary spastic paraplegia and optic atrophy type 1, and behavior disorders like neuropsychiatric, hyperactivity and autism spectrum disorders are closely associated with neurobiological deficits. Brain derived neurotrophic factor (BDNF) is an extensively studied neurotrophin. BDNF is essential for neuronal genesis, differentiation, survival, growth, plasticity, synaptic viability and transmission. BDNF has emerged as a promising target for regulating synaptic activity and plasticity. An overview of effects and mechanisms of the natural products targeting BDNF is described. This review is an attempt to enumerate the effects of various natural products on BDNF as a novel therapeutic approach for neurodegenerative and neuropsychiatric disorders.

PMID: 31546015 [PubMed – as supplied by publisher]

PMID:
PubMed:31546015

DATE FOUND:
09/24/19 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31546015?dopt=Abstract

Extension Study of Ampreloxetine (TD-9855) for Treating snOH in Subjects With Primary Autonomic Failure

https://clinicaltrials.gov/ct2/show/NCT04095793?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=09%2F05%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Extension Study of Ampreloxetine (TD-9855) for Treating snOH in Subjects With Primary Autonomic Failure

DESCRIPTION:
Condition:   Symptomatic Neurogenic Orthostatic Hypotension
Intervention:   Drug: ampreloxetine
Sponsor:   Theravance Biopharma
Not yet recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT04095793

FIRST POSTED:
Thu, 19 Sep 2019 12:00:00 EDT

LAST UPDATE POSTED:
09/19/19 08:06AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT04095793?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=09%2F05%2F2019&lupd_d=14&sort=nwst

Study to Evaluate DNL151 in Subjects With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT04056689?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=07%2F31%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Study to Evaluate DNL151 in Subjects With Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: DNL151 low dose;   Drug: DNL151 high dose;   Drug: Placebo
Sponsor:   Denali Therapeutics Inc.
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT04056689

FIRST POSTED:
Wed, 14 Aug 2019 12:00:00 EDT

LAST UPDATE POSTED:
08/14/19 07:51AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT04056689?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=07%2F31%2F2019&lupd_d=14&sort=nwst

A Study of Weekly Subcutaneous Injections of SER-214 in Subjects With Parkinson’s Disease (PD), to Determine the Safety, Tolerability and Pharmacokinetic (PK) Profile of SER-214

https://clinicaltrials.gov/ct2/show/NCT02579473?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=09%2F04%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Study of Weekly Subcutaneous Injections of SER-214 in Subjects With Parkinson’s Disease (PD), to Determine the Safety, Tolerability and Pharmacokinetic (PK) Profile of SER-214

DESCRIPTION:
Condition:   Parkinson’s Disease
Intervention:   Drug: SER-214
Sponsor:   Serina Therapeutics
Active, not recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT02579473

FIRST POSTED:
Mon, 19 Oct 2015 12:00:00 EDT

LAST UPDATE POSTED:
09/18/19 07:46AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT02579473?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=09%2F04%2F2019&lupd_d=14&sort=nwst

Prostate drug (terazosin) may slow Parkinson’s disease

https://www.bbc.com/news/health-49713407

Prostate drug may slow Parkinson’s disease

A drug used to treat enlarged prostates may be a powerful medicine against Parkinson’s disease, according to an international team of scientists.

#terazosin

Open-label Investigation of the Safety and Clinical Effects of NTCELL in Patients With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT01734733?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=09%2F02%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Open-label Investigation of the Safety and Clinical Effects of NTCELL in Patients With Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson’s Disease
Intervention:   Other: NTCELL
Sponsor:   Living Cell Technologies
Active, not recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT01734733

FIRST POSTED:
Wed, 28 Nov 2012 12:00:00 EST

LAST UPDATE POSTED:
09/16/19 07:45AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT01734733?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=09%2F02%2F2019&lupd_d=14&sort=nwst

Mitochondrial CHCHD2 and CHCHD10: Roles in Neurological Diseases and Therapeutic Implications

https://journals.sagepub.com/doi/abs/10.1177/1073858419871214?journalCode=nroa

https://www.ncbi.nlm.nih.gov/pubmed/31526091?dopt=Abstract

TITLE:
Mitochondrial CHCHD2 and CHCHD10: Roles in Neurological Diseases and Therapeutic Implications.

DESCRIPTION:
Related Articles

Mitochondrial CHCHD2 and CHCHD10: Roles in Neurological Diseases and Therapeutic Implications.

Neuroscientist. 2019 Sep 16;:1073858419871214

Authors: Zhou W, Ma D, Tan EK

Abstract

CHCHD2 mutations have been identified in various neurological diseases such as Parkinson’s disease (PD), frontotemporal dementia (FTD), and Alzheimer’s disease (AD). It is also the first mitochondrial gene whose mutations lead to PD. CHCHD10 is a homolog of CHCHD2; similar to CHCHD2, various mutations of CHCHD10 have been identified in a broad spectrum of neurological disorders, including FTD and AD, with a high frequency of CHCHD10 mutations found in motor neuron diseases. Functionally, CHCHD2 and CHCHD10 have been demonstrated to interact with each other in mitochondria. Recent studies link the biological functions of CHCHD2 to the MICOS complex (mitochondrial inner membrane organizing system). Multiple experimental models suggest that CHCHD2 maintains mitochondrial cristae and disease-associated CHCHD2 mutations function in a loss-of-function manner. However, both CHCHD2 and CHCHD10 knockout mouse models appear phenotypically normal, with no obvious mitochondrial defects. Strategies to maintain or enhance mitochondria cristae could provide opportunities to correct the associated cellular defects in disease state and unravel potential novel targets for CHCHD2-linked neurological conditions.

PMID: 31526091 [PubMed – as supplied by publisher]

PMID:
PubMed:31526091

DATE FOUND:
09/19/19 06:01AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31526091?dopt=Abstract

Protective and Regenerative Roles of T Cells in Central Nervous System Disorders

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751344/

https://www.ncbi.nlm.nih.gov/pubmed/31572381?dopt=Abstract

TITLE:
Protective and Regenerative Roles of T Cells in Central Nervous System Disorders.

DESCRIPTION:
Protective and Regenerative Roles of T Cells in Central Nervous System Disorders.

Front Immunol. 2019;10:2171

Authors: Evans FL, Dittmer M, de la Fuente AG, Fitzgerald DC

Abstract

Pathogenic mechanisms of T cells in several central nervous system (CNS) disorders are well-established. However, more recent studies have uncovered compelling beneficial roles of T cells in neurological diseases, ranging from tissue protection to regeneration. These divergent functions arise due to the diversity of T cell subsets, particularly CD4+ T cells. Here, we review the beneficial impact of T cell subsets in a range of neuroinflammatory and neurodegenerative diseases including multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and CNS trauma. Both T cell-secreted mediators and direct cell contact-dependent mechanisms deliver neuroprotective, neuroregenerative and immunomodulatory signals in these settings. Understanding the molecular details of these beneficial T cell mechanisms will provide novel targets for therapeutic exploitation that can be applied to a range of neurological disorders.

PMID: 31572381 [PubMed – in process]

PMID:
PubMed:31572381

DATE FOUND:
10/02/19 06:50AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31572381?dopt=Abstract

Study to Investigate the Effect of IPT803 Adjunct Treatment in Patients With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03407378?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=08%2F05%2F2019&lupd_d=14&sort=nwst

A Proof of Concept Study to Investigate the Effect of IPT803 Adjunct Treatment in Patients With Parkinson’s Disease

STUDY TITLE:
A Study to Investigate a New Treatment in Patients With Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: IPT803;   Genetic: Optional pharmacogenetic assessment;   Other: Questionnaires;   Other: Optional Blood-Oxygen-level Dependent functionalMRI;   Other: Motor Assessments before taking regular PD treatment;   Other: Motor Assessments on regular PD treatment
Sponsor:   Tools4Patient
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03407378

FIRST POSTED:
Tue, 23 Jan 2018 12:00:00 EST

LAST UPDATE POSTED:
08/19/19 10:02AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03407378?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=08%2F05%2F2019&lupd_d=14&sort=nwst

Biogen begins recruiting patients for phase 1 clinical trial of BIIB094 for Parkinson’s disease

According to ClinicalTrials.gov, the BIIB094 study record was updated on August 26, 2019. That is when the recruitment status of the study was changed from Not Yet Recruiting to Recruiting.

The estimated enrollment (number of patients able to participate in this phase of the trial) is 62 and the study is scheduled to start on September 21, 2019. (Which suggests that anyone who wants to participate in this trial should probably hurry – while there are still spots remaining.)

Here is some more information from the official BIIB094 clinical trial page and also a link to the study page where you can find all the important details, contact information, and so on.

The primary objective of this study is to evaluate the safety and tolerability of single and multiple doses of BIIB094 administered via intrathecal (IT) injection to participants with Parkinson’s Disease (PD). The secondary objective of this study is to evaluate the pharmacokinetic (PK) profile of BIIB094. The study is open for PD patients with verified presence or absence of mutations in the leucine-rich repeated kinase 2 (LRRK2) gene, but also for patients without any verified PD-related genetic mutation.

STUDY LINK: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB094 in Adults With Parkinson’s Disease

LOCATIONS (Where is the study taking place?)

The study is currently recruiting in 3 locations: Michigan, Tennessee, and Washington.

COMMENT: For more Parkinson’s disease treatment-related updates and news via email, subscribe. For questions or comments to help improve this site, email michael@urgentresearch.com and say hello.

Essential role of phosphodiesterase 7 (PDE7) enzyme in neurodegeneration and inflammatory-mediated brain damage opens door to new therapeutic interventions for Parkinson’s disease

https://link.springer.com/article/10.1007%2Fs12035-019-01745-z

https://www.ncbi.nlm.nih.gov/pubmed/31473904?dopt=Abstract

TITLE:
Phosphodiesterase 7 Regulation in Cellular and Rodent Models of Parkinson’s Disease.

DESCRIPTION:
Phosphodiesterase 7 Regulation in Cellular and Rodent Models of Parkinson’s Disease.

Mol Neurobiol. 2019 Aug 31;:

Authors: Morales-Garcia JA, Alonso-Gil S, Santos Á, Perez-Castillo A

Abstract

Parkinson’s disease is characterized by a loss of dopaminergic neurons in the ventral midbrain. This disease is diagnosed when around 50% of these neurons have already died; consequently, therapeutic treatments start too late. Therefore, an urgent need exists to find new targets involved in the onset and progression of the disease. Phosphodiesterase 7 (PDE7) is a key enzyme involved in the degradation of intracellular levels of cyclic adenosine 3′, 5′-monophosphate in different cell types; however, little is known regarding its role in neurodegenerative diseases, and specifically in Parkinson’s disease. We have previously shown that chemical as well as genetic inhibition of this enzyme results in neuroprotection and anti-inflammatory activity in different models of neurodegenerative disorders, including Parkinson’s disease. Here, we have used in vitro and in vivo models of Parkinson’s disease to study the regulation of PDE7 protein levels. Our results show that PDE7 is upregulated after an injury both in the human dopaminergic cell line SH-SY5Y and in primary rat mesencephalic cultures and after lipopolysaccharide or 6-hidroxydopamine injection in the Substantia nigra pars compacta of adult mice. PDE7 increase takes place mainly in degenerating dopaminergic neurons and in microglia cells. This enhanced expression appears to be direct since 6-hydroxydopamine and lipopolysaccharide increase the expression of a 962-bp fragment of its promoter. Taking together, these results reveal an essential function for PDE7 in the pathways leading to neurodegeneration and inflammatory-mediated brain damage and suggest novel roles for PDE7 in neurodegenerative diseases, specifically in PD, opening the door for new therapeutic interventions.

PMID: 31473904 [PubMed – as supplied by publisher]

PMID:
PubMed:31473904

DATE FOUND:
09/02/19 06:02AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31473904?dopt=Abstract

Hepcidin and its therapeutic potential in neurodegenerative disorders

https://onlinelibrary.wiley.com/doi/abs/10.1002/med.21631

https://www.ncbi.nlm.nih.gov/pubmed/31471929?dopt=Abstract

TITLE:
Hepcidin and its therapeutic potential in neurodegenerative disorders.

DESCRIPTION:
Related Articles

Hepcidin and its therapeutic potential in neurodegenerative disorders.

Med Res Rev. 2019 Aug 30;:

Authors: Qian ZM, Ke Y

Abstract

Abnormally high brain iron, resulting from the disrupted expression or function of proteins involved in iron metabolism in the brain, is an initial cause of neuronal death in neuroferritinopathy and aceruloplasminemia, and also plays a causative role in at least some of the other neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Friedreich’s ataxia. As such, iron is believed to be a novel target for pharmacological intervention in these disorders. Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron-related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood-brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron-associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.

PMID: 31471929 [PubMed – as supplied by publisher]

PMID:
PubMed:31471929

DATE FOUND:
09/01/19 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31471929?dopt=Abstract

Study of UB-312 in Healthy Participants and Parkinson’s Disease Patients

https://clinicaltrials.gov/ct2/show/NCT04075318?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=08%2F16%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Study of UB-312 in Healthy Participants and Parkinson’s Disease Patients

DESCRIPTION:
Conditions:   Parkinson Disease;   Parkinsonism
Interventions:   Biological: UB-312;   Biological: Placebo
Sponsors:   United Neuroscience Ltd.;   Centre for Human Drug Research, Netherlands;   Worldwide Clinical Trials
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT04075318

FIRST POSTED:
Fri, 30 Aug 2019 12:00:00 EDT

LAST UPDATE POSTED:
08/30/19 09:00AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT04075318?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=08%2F16%2F2019&lupd_d=14&sort=nwst

Study of OXB-102 (AXO-Lenti-PD) in Patients With Bilateral, Idiopathic Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03720418?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=08%2F16%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Study of OXB-102 (AXO-Lenti-PD) in Patients With Bilateral, Idiopathic Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: OXB-102;   Other: Imitation Surgical Procedure (ISP)
Sponsors:   Axovant Sciences Ltd.;   Oxford BioMedica
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03720418

FIRST POSTED:
Thu, 25 Oct 2018 12:00:00 EDT

LAST UPDATE POSTED:
08/30/19 09:00AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03720418?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=08%2F16%2F2019&lupd_d=14&sort=nwst

Current Progress of Mitochondrial Quality Control Pathways Underlying the Pathogenesis of Parkinson’s Disease

https://www.hindawi.com/journals/omcl/2019/4578462/

https://www.ncbi.nlm.nih.gov/pubmed/31485291?dopt=Abstract

TITLE:
Current Progress of Mitochondrial Quality Control Pathways Underlying the Pathogenesis of Parkinson’s Disease.

DESCRIPTION:
Related Articles

Current Progress of Mitochondrial Quality Control Pathways Underlying the Pathogenesis of Parkinson’s Disease.

Oxid Med Cell Longev. 2019;2019:4578462

Authors: Jiang X, Jin T, Zhang H, Miao J, Zhao X, Su Y, Zhang Y

Abstract

Parkinson’s disease (PD), clinically characterized by motor and nonmotor symptoms, is a common progressive and multisystem neurodegenerative disorder, which is caused by both genetic and environmental risk factors. The main pathological features of PD are the loss of dopaminergic (DA) neurons and the accumulation of alpha-synuclein (α-syn) in the residual DA neurons in the substantia nigra pars compacta (SNpc). In recent years, substantial progress has been made in discovering the genetic factors of PD. In particular, a total of 19 PD-causing genes have been unraveled, among which some members have been regarded to be related to mitochondrial dysfunction. Mitochondria are key regulators of cellular metabolic activity and are critical for many important cellular processes including energy metabolism and even cell death. Their normal function is basically maintained by the mitochondrial quality control (MQC) mechanism. Accordingly, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a kind of neurotoxin, exerts its neurotoxic effects at least partially by producing its toxic metabolite, namely, 1-methyl-4-phenylpyridine (MPP+), which in turn causes mitochondrial dysfunction by inhibiting complex I and mimicking the key features of PD pathogenesis. This review focused on three main aspects of the MQC signaling pathways, that is, mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy; hence, it demonstrates in detail how genetic and environmental factors result in PD pathogenesis by interfering with MQC pathways, thereby hopefully contributing to the discovery of novel potential therapeutic targets for PD.

PMID: 31485291 [PubMed – in process]

PMID:
PubMed:31485291

DATE FOUND:
09/06/19 07:13AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31485291?dopt=Abstract

SRC Inhibition as a Potential Target for Parkinson’s Disease Psychosis

https://clinicaltrials.gov/ct2/show/NCT03661125?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=07%2F30%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
SRC Inhibition as a Potential Target for Parkinson’s Disease Psychosis

DESCRIPTION:
Condition:   Parkinson Disease Psychosis
Interventions:   Drug: Saracatinib;   Drug: Placebo Oral Tablet
Sponsors:   King’s College London;   AstraZeneca;   King’s College Hospital NHS Trust
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03661125

FIRST POSTED:
Fri, 07 Sep 2018 12:00:00 EDT

LAST UPDATE POSTED:
08/13/19 06:58AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03661125?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=07%2F30%2F2019&lupd_d=14&sort=nwst

The gut microbiota: A novel therapeutic target in Parkinson’s disease?

https://www.prd-journal.com/article/S1353-8020(19)30366-9/fulltext

https://www.ncbi.nlm.nih.gov/pubmed/31445904?dopt=Abstract

TITLE:
The gut microbiota: A novel therapeutic target in Parkinson’s disease?

DESCRIPTION:
Related Articles

The gut microbiota: A novel therapeutic target in Parkinson’s disease?

Parkinsonism Relat Disord. 2019 Aug 12;:

Authors: Lubomski M, Davis RL, Sue CM

PMID: 31445904 [PubMed – as supplied by publisher]

PMID:
PubMed:31445904

DATE FOUND:
08/26/19 06:02AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31445904?dopt=Abstract

P1 Receptor Agonists/Antagonists – Potential Parkinson’s Drug Candidates of the Future

http://www.eurekaselect.com/173523/article

https://www.ncbi.nlm.nih.gov/pubmed/31333097?dopt=Abstract

TITLE:
P1 Receptor Agonists/Antagonists in Clinical Trials – Potential Drug Candidates of the Future.

DESCRIPTION:
Related Articles

P1 Receptor Agonists/Antagonists in Clinical Trials – Potential Drug Candidates of the Future.

Curr Pharm Des. 2019 Jul 16;:

Authors: Borah P, Deka S, Mailavaram RP, Deb PK

Abstract

BACKGROUND: Adenosine mediates various physiological and pathological conditions by acting on its four P1 receptors (A1, A2A, A2B and A3 receptors). Omnipresence of P1 receptors and their activation, exert a wide range of biological activities. Thus its modulation is implicated in various disorders like Parkinson’s disease, asthma, cardiovascular disorders, cancer etc. Hence this has become an interesting target for the researchers to develop potential therapeutic agents. Number of molecules were designed and developed in the past few years and evaluated for their efficacy in various disease conditions.

OBJECTIVE: The main objective is to provide an overview of new chemical entities which have crossed preclinical studies and reached clinical trials stage following their current status and future prospective.

METHODS: In this review we discuss current status of the drug candidates which have undergone clinical trials and their prospects.

RESULTS: Many chemical entities targeting various subtypes of P1 receptors are patented; twenty of them have crossed preclinical studies and reached clinical trials stage. Two of them viz adenosine and regadenoson are approved by Food and Drug Administration.

CONCLUSION: This review is an attempt to highlight the current status, progress and probable future of P1 receptor ligands which are under clinical trials as promising novel therapeutic agents and the direction in which research should proceed with a view to come out with novel therapeutic agents.

PMID: 31333097 [PubMed – as supplied by publisher]

PMID:
PubMed:31333097

DATE FOUND:
07/24/19 10:11AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31333097?dopt=Abstract

Nobiletin, a citrus flavonoid, has the potential to become a novel drug for the treatment of Parkinson’s, according to researchers in Japan

The new study was published online in the International Journal of Molecular Science on July 10, 2019.

You can read the full paper here: Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer’s Disease and Parkinson’s Disease.

Here is the abstract:

Alzheimer’s disease (AD), which is characterized by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles, accompanied by neurodegeneration, is the most common form of age-related neurodegenerative disease. Parkinson’s disease (PD) is the second most common neurodegenerative disease after AD, and is characterized by early prominent loss of dopaminergic neurons in the substantia nigra pars compacta. As currently available treatments are not able to significantly alter the progression of these diseases, successful therapeutic and preventive interventions are strongly needed. In the course of our survey of substances from natural resources having anti-dementia and neuroprotective activity, we found nobiletin, a polymethoxylated flavone from the peel of Citrus depressa. Nobiletin improved cognitive deficits and the pathological features of AD, such as Aβ pathology, hyperphosphorylation of tau, and oxidative stress, in animal models of AD. In addition, nobiletin improved motor and cognitive deficits in PD animal models. These observations suggest that nobiletin has the potential to become a novel drug for the treatment and prevention of neurodegenerative diseases such as AD and PD.

Int J Mol Sci. 2019 Jul 10;20(14):
Authors: Nakajima A, Ohizumi Y

For more information and science related to the citrus in question, Citrus depressa – “a small, green citrus fruit rich in flavonoids and native to Taiwan and Okinawa, Japan” – here are some more links:

https://en.wikipedia.org/wiki/Citrus_depressa

https://idtools.org/id/citrus/citrusid/factsheet.php?name=Shekwasha

https://www.science.gov/topicpages/s/shiikuwasha+citrus+depressa.html

Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator

https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00163

https://www.ncbi.nlm.nih.gov/pubmed/31312409?dopt=Abstract

TITLE:
Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator.

DESCRIPTION:
Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator.

ACS Med Chem Lett. 2019 Jul 11;10(7):1061-1067

Authors: Choi JW, Shin SJ, Kim HJ, Park JH, Kim HJ, Lee EH, Pae AN, Bahn YS, Park KD

Abstract

The main pathway responsible for cellular regulation against oxidative stress is nuclear factor E2-related factor-2 (Nrf2) signaling. We previously synthesized and reported a novel vinyl sulfone (1) as an Nrf2 activator with therapeutic potential for Parkinson’s disease (PD). In this study, we changed the vinyl sulfone to vinyl sulfonamide or vinyl sulfonate to improve Nrf2 activating efficacy. We observed that the introduction of vinyl sulfonamide led to a reduction of the effects on Nrf2 activation, whereas vinyl sulfonate compounds exhibited superior activity compared to the vinyl sulfone compounds. Among the vinyl sulfonates, 3c exhibited 6.9- and 83.5-fold higher effects on Nrf2 activation than the corresponding vinyl sulfone (1) and vinyl sulfonamide (2c), respectively. Compound 3c was confirmed to induce expression of the Nrf2-dependent antioxidant enzymes at the protein level in cells. In addition, 3c mitigated PD-associated behavioral deficits by protecting DAergic neurons in the MPTP-induced mouse model of PD.

PMID: 31312409 [PubMed]

PMID:
PubMed:31312409

DATE FOUND:
07/18/19 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31312409?dopt=Abstract

Cysteamine as a novel disease-modifying compound for Parkinson’s disease: Over a decade of research supporting a clinical trial

https://www.sciencedirect.com/science/article/pii/S0969996119301986?via%3Dihub

https://www.ncbi.nlm.nih.gov/pubmed/31301344?dopt=Abstract

TITLE:
Cysteamine as a novel disease-modifying compound for Parkinson’s disease: Over a decade of research supporting a clinical trial.

DESCRIPTION:
Cysteamine as a novel disease-modifying compound for Parkinson’s disease: Over a decade of research supporting a clinical trial.

Neurobiol Dis. 2019 Jul 10;:104530

Authors: Cicchetti F, David LS, Siddu A, Denis HL

Abstract

To date, medical and surgical interventions offered to patients with Parkinson’s disease (PD) serve only to manage clinical symptoms; they have not shown the capacity to halt nor reverse degenerative processes. There is therefore an urgent need to identify and/or develop therapeutic strategies that will demonstrate ‘disease modifying’ capacities. The molecule cystamine, and its reduced form cysteamine, act via a number of pathways identified as being critical to the pathogenesis of PD. In particular, these agents are capable of crossing the blood-brain barrier, promoting the secretion of neurotrophic factors, the inhibition of oxidative stress, the reduction of inflammatory responses and importantly, have already been trialed in humans for a number of other clinical indications. In the last decade, our laboratory has accumulated compelling evidence that both cystamine and cysteamine can halt, and even reverse, ongoing neurodegenerative processes in a number of different models of PD, and as such, should now be taken forward to clinical trials in PD.

PMID: 31301344 [PubMed – as supplied by publisher]

PMID:
PubMed:31301344

DATE FOUND:
07/14/19 06:01AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31301344?dopt=Abstract

Potential Benefits of Nobiletin, A Citrus Flavonoid, against Parkinson’s Disease

https://www.mdpi.com/1422-0067/20/14/3380/htm

https://www.ncbi.nlm.nih.gov/pubmed/31295812?dopt=Abstract

TITLE:
Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer’s Disease and Parkinson’s Disease.

DESCRIPTION:
Potential Benefits of Nobiletin, A Citrus Flavonoid, against Alzheimer’s Disease and Parkinson’s Disease.

Int J Mol Sci. 2019 Jul 10;20(14):

Authors: Nakajima A, Ohizumi Y

Abstract

Alzheimer’s disease (AD), which is characterized by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles, accompanied by neurodegeneration, is the most common form of age-related neurodegenerative disease. Parkinson’s disease (PD) is the second most common neurodegenerative disease after AD, and is characterized by early prominent loss of dopaminergic neurons in the substantia nigra pars compacta. As currently available treatments are not able to significantly alter the progression of these diseases, successful therapeutic and preventive interventions are strongly needed. In the course of our survey of substances from natural resources having anti-dementia and neuroprotective activity, we found nobiletin, a polymethoxylated flavone from the peel of Citrus depressa. Nobiletin improved cognitive deficits and the pathological features of AD, such as Aβ pathology, hyperphosphorylation of tau, and oxidative stress, in animal models of AD. In addition, nobiletin improved motor and cognitive deficits in PD animal models. These observations suggest that nobiletin has the potential to become a novel drug for the treatment and prevention of neurodegenerative diseases such as AD and PD.

PMID: 31295812 [PubMed – in process]

PMID:
PubMed:31295812

DATE FOUND:
07/13/19 06:01AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31295812?dopt=Abstract

Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease

https://www.tandfonline.com/doi/full/10.1080/10717544.2019.1636420

https://www.ncbi.nlm.nih.gov/pubmed/31290705?dopt=Abstract

TITLE:
Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease.

DESCRIPTION:
Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease.

Drug Deliv. 2019 Dec;26(1):700-707

Authors: Tang S, Wang A, Yan X, Chu L, Yang X, Song Y, Sun K, Yu X, Liu R, Wu Z, Xue P

Abstract

Efficient delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate borneol and lactoferrin co-modified nanoparticles (Lf-BNPs) encapsulated dopamine as a novel drug delivery system to achieve maximum therapeutic efficacy and reduce side effects for PD. Dopamine Lf-BNPs were prepared using the double emulsion solvent evaporation method and evaluated for physicochemical and pharmaceutical properties. In vitro cytotoxicity studies indicated that treatment with dopamine Lf-BNPs has relatively low cytotoxicity in SH-SY5Y and 16HBE cells. Qualitative and quantitative cellular uptake experiments indicated that Lf modification of NPs increased cellular uptake of SH-SY5Y cells and 16HBE cells, and borneol modification can promote the cellular uptake of 16HBE. In vivo pharmacokinetic studies indicated that AUC0-12 h in the rat brain for dopamine Lf-BNPs was significantly higher (p < .05) than that of dopamine nanoparticles. Intranasal administration of dopamine Lf-BNPs effectively alleviated the 6-hydroxydopamine-induced striatum lesion in rats as indicated by the contralateral rotation behavior test and results for striatal monoamine neurotransmitter content detection. Taken together, intranasal administration of dopamine Lf-BNPs may be an effective drug delivery system for Parkinson’s disease.

PMID: 31290705 [PubMed – in process]

PMID:
PubMed:31290705

DATE FOUND:
07/11/19 02:42PM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31290705?dopt=Abstract

Neurocrine Biosciences Announces FDA Acceptance of New Drug Application for Opicapone as an Adjunctive Treatment for Patients with Parkinson’s Disease

https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-fda-acceptance-of-new-drug-application-for-opicapone-as-an-adjunctive-treatment-for-patients-with-parkinsons-disease-300882953.html

Neurocrine Biosciences Announces FDA Acceptance of New Drug Application for Opicapone as an Adjunctive Treatment for Patients with Parkinson’s Disease

The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson’s disease

https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27779

https://www.ncbi.nlm.nih.gov/pubmed/31291491?dopt=Abstract

TITLE:
The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson’s disease.

DESCRIPTION:
The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson’s disease.

Mov Disord. 2019 Jul 10;:

Authors: Moosa S, Martínez-Fernández R, Elias WJ, Del Alamo M, Eisenberg HM, Fishman PS

Abstract

MR-guided focused ultrasound is a novel, minimally invasive surgical procedure for symptomatic treatment of PD. With this technology, the ventral intermediate nucleus, STN, and internal globus pallidus have been targeted for therapeutic cerebral ablation, while also minimizing the risk of hemorrhage and infection from more invasive neurosurgical procedures. In a double-blinded, prospective, sham-controlled randomized controlled trial of MR-guided focused ultrasound thalamotomy for treatment of tremor-dominant PD, 62% of treated patients demonstrated improvement in tremor scores from baseline to 3 months postoperatively, as compared to 22% in the sham group. There has been only one open-label trial of MR-guided focused ultrasound subthalamotomy for patients with PD, demonstrating improvements of 71% for rigidity, 36% for akinesia, and 77% for tremor 6 months after treatment. Among the two open-label trials of MR-guided focused ultrasound pallidotomy for patients with PD, dyskinesia and overall motor scores improved up to 52% and 45% at 6 months postoperatively. Although MR-guided focused ultrasound thalamotomy is now approved by the U.S. Food and Drug Administration for treatment of parkinsonian tremor, additional high-quality randomized controlled trials are warranted and are underway to determine the safety and efficacy of MR-guided focused ultrasound subthalamotomy and pallidotomy for treatment of the cardinal features of PD. These studies will be paramount to aid clinicians to determine the ideal ablative target for individual patients. Additional work will be required to assess the durability of MR-guided focused ultrasound lesions, ideal timing of MR-guided focused ultrasound ablation in the course of PD, and the safety of performing bilateral lesions. © 2019 International Parkinson and Movement Disorder Society.

PMID: 31291491 [PubMed – as supplied by publisher]

PMID:
PubMed:31291491

DATE FOUND:
07/11/19 02:42PM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31291491?dopt=Abstract

Prevail Therapeutics Receives U.S. FDA Fast Track Designation for PR001 for the Treatment of Parkinson’s Disease Patients with a GBA1 Mutation, Plans to Initiate Phase 1/2 Clinical Trial in the Second Half of 2019

https://www.globenewswire.com/news-release/2019/07/08/1879407/0/en/Prevail-Therapeutics-Receives-U-S-FDA-Fast-Track-Designation-for-PR001-for-the-Treatment-of-Parkinson-s-Disease-Patients-with-a-GBA1-Mutation.html

Prevail Therapeutics Receives U.S. FDA Fast Track Designation for PR001 for the Treatment of Parkinson’s Disease Patients with a GBA1 Mutation

Company Plans to Initiate Phase 1/2 Clinical Trial in the Second Half of 2019

Recently identified therapeutic targets in dystonia based on recent preclinical animal studies and clinical trials investigating novel therapeutics

https://www.ncbi.nlm.nih.gov/pubmed/31279827?dopt=Abstract

TITLE:
The neurobiological basis for novel experimental therapeutics in dystonia.

DESCRIPTION:
Related Articles

The neurobiological basis for novel experimental therapeutics in dystonia.

Neurobiol Dis. 2019 Jul 04;:104526

Authors: Downs AM, Roman KM, Campbell SA, Pisani A, Hess EJ, Bonsi P

Abstract

Dystonia is a movement disorder characterized by involuntary muscle contractions, twisting movements, and abnormal postures that may affect one or multiple body regions. Dystonia is the third most common movement disorder after Parkinson’s disease and essential tremor. Despite its relative frequency, small molecule therapeutics for dystonia are limited. Development of new therapeutics is further hampered by the heterogeneity of both clinical symptoms and etiologies in dystonia. Recent advances in both animal and cell-based models have helped clarify divergent etiologies in dystonia and have facilitated the identification of new therapeutic targets. Advances in medicinal chemistry have also made available novel compounds for testing in biochemical, physiological, and behavioral models of dystonia. Here, we briefly review motor circuit anatomy and the anatomical and functional abnormalities in dystonia. We then discuss recently identified therapeutic targets in dystonia based on recent preclinical animal studies and clinical trials investigating novel therapeutics.

PMID: 31279827 [PubMed – as supplied by publisher]

PMID:
PubMed:31279827

DATE FOUND:
07/08/19 06:00AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31279827?dopt=Abstract

Protein glycation: An emerging new medicinal target area for Parkinson’s disease

https://www.ncbi.nlm.nih.gov/pubmed/31272349?dopt=Abstract

http://www.eurekaselect.com/173223/article

TITLE:
Protein glycation: An old villain is shedding secrets.

DESCRIPTION:
Related Articles

Protein glycation: An old villain is shedding secrets.

Comb Chem High Throughput Screen. 2019 Jul 03;:

Authors: Lushington GH, Barnes AC

Abstract

The glycation of proteins is a non-physiological post-translational incorporation of carbohydrates onto the free amines or guanidines of proteins and some lipids. Although the existence of glycated proteins has been known for forty years, a full understanding of their pathogenic nature has been slow in accruing. In recent years, however, glycation has gained wide-spread acceptance as a contributing factor in numerous metabolic, autoimmune and neurological disorders, tying together several confounding aspects of disease etiology. From diabetes, arthritis and lupus, to multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s diseases, an emerging glycation / inflammation paradigm now offers significant new insight into a physiologically important toxicological phenomenon. It exposes novel drug targets and treatment options, and may even lay foundations for long-awaited breakthroughs. This ‘current frontier’ article briefly profiles current knowledge regarding the underlying causes of glycation, the structural biology implications of such modifications and their pathological consequences. Although several emerging therapeutic strategies for addressing glycation pathologies are introduced, the primary purpose of this mini-review is to raise awareness of the challenges and opportunities inherent in this emerging new medicinal target area.

PMID: 31272349 [PubMed – as supplied by publisher]

PMID:
PubMed:31272349

DATE FOUND:
07/06/19 06:00AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31272349?dopt=Abstract

Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03295786?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=06%2F21%2F2019&lupd_d=14&sort=nwst

Phase 1-2, Randomised, Double-Blind, Placebo Controlled, Safety and Tolerability Study of Intraputamenal Cerebral Dopamine Neurotrophic Factor (CDNF) Infusions Via an Investigational Drug Delivery System to Patients With Parkinson’s Disease

STUDY TITLE:
Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson’s Disease

DESCRIPTION:
Conditions:   Parkinson Disease;   Movement Disorders;   Neurodegenerative Diseases;   Nervous System Diseases;   Brain Diseases
Interventions:   Drug: Cerebral Dopamine Neurotrophic Factor;   Device: Renishaw Drug Delivery System
Sponsors:   Herantis Pharma Plc.;   Renishaw plc.
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03295786

FIRST POSTED:
Thu, 28 Sep 2017 12:00:00 EDT

LAST UPDATE POSTED:
07/05/19 07:10AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03295786?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=06%2F21%2F2019&lupd_d=14&sort=nwst

A Clinical Trial Investigating the Efficacy, Safety and Tolerability of ND0612 Infusion in Subjects With Parkinson’s Disease Experiencing Motor Fluctuations

https://clinicaltrials.gov/ct2/show/NCT04006210?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=06%2F21%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Clinical Trial Investigating the Efficacy, Safety and Tolerability of Continuous Subcutaneous ND0612 Infusion in Comparison to Oral IR-LD/CD in Subjects With Parkinson’s Disease Experiencing Motor Fluctuations (BouNDless).

DESCRIPTION:
Condition:   Parkinson’s Disease
Interventions:   Combination Product: ND0612 Solution for SC infusion;   Combination Product: Placebo for SC infusion;   Drug: Carbidopa and Levodopa 25mg/100mg;   Drug: Placebo for Carbidopa and Levodopa 25mg/100mg
Sponsor:   NeuroDerm Ltd.
Not yet recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT04006210

FIRST POSTED:
Wed, 03 Jul 2019 12:00:00 EDT

LAST UPDATE POSTED:
07/05/19 07:10AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT04006210?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=06%2F21%2F2019&lupd_d=14&sort=nwst

Emerald Health Pharmaceuticals Demonstrates Neuroprotective Activity of Novel Cannabigerol Derivatives in Huntington’s and Parkinson’s Disease Models

https://www.globenewswire.com/news-release/2019/07/02/1877328/0/en/Emerald-Health-Pharmaceuticals-Demonstrates-Neuroprotective-Activity-of-Novel-Cannabigerol-Derivatives-in-Huntington-s-and-Parkinson-s-Disease-Models.html

Emerald Health Pharmaceuticals Demonstrates Neuroprotective Activity of Novel Cannabigerol Derivatives in Huntington’s and Parkinson’s Disease Models

Seelos Therapeutics Announces Acquisition of an Exclusive Worldwide License of Gene Therapy Program to Address Parkinson’s Disease from Duke University

https://www.globenewswire.com/news-release/2019/06/27/1875104/0/en/Seelos-Therapeutics-Announces-Acquisition-of-an-Exclusive-Worldwide-License-of-Gene-Therapy-Program-to-Address-Parkinson-s-Disease-from-Duke-University.html

Seelos Therapeutics Announces Acquisition of an Exclusive Worldwide License of Gene Therapy Program to Address Parkinson’s Disease from Duke University