Parkinson’s Treatment Report

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Dose Escalation Study of Cu(II)ATSM in Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03204929?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=06%2F11%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Dose Escalation Study of Cu(II)ATSM in Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Intervention:   Drug: Cu(II)ATSM
Sponsor:   Collaborative Medicinal Development Pty Limited
Active, not recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03204929

FIRST POSTED:
Sun, 02 Jul 2017 12:00:00 EDT

LAST UPDATE POSTED:
06/25/19 06:51AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03204929?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=06%2F11%2F2019&lupd_d=14&sort=nwst

Safinamide for Levodopa-induced Dyskinesia (PD-LID)

https://clinicaltrials.gov/ct2/show/NCT03987750?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=06%2F03%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Safinamide for Levodopa-induced Dyskinesia (PD-LID)

DESCRIPTION:
Conditions:   Dyskinesia, Drug-Induced;   Parkinson Disease
Interventions:   Drug: Safinamide Methanesulfonate 150mg;   Drug: Safinamide Methanesulfonate 100mg;   Drug: Safinamide Methanesulfonate matching placebo
Sponsor:   Zambon SpA
Not yet recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03987750

FIRST POSTED:
Mon, 17 Jun 2019 12:00:00 EDT

LAST UPDATE POSTED:
06/17/19 07:43AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03987750?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=06%2F03%2F2019&lupd_d=14&sort=nwst

Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism

https://science.sciencemag.org/content/364/6445/eaau6323

RESEARCH ARTICLE
Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism
Vayu Maini Rekdal1, Elizabeth N. Bess2,3,4, Jordan E. Bisanz2, Peter J. Turnbaugh2,5,*, Emily P. Balskus1,*
See all authors and affiliations

Science 14 Jun 2019:
Vol. 364, Issue 6445, eaau6323
DOI: 10.1126/science.aau6323

Gut microbes metabolize Parkinson’s disease drug

https://science.sciencemag.org/content/364/6445/1030

Gut microbes metabolize Parkinson’s disease drug
Cora O’Neill1,2,3
See all authors and affiliations

Science 14 Jun 2019:
Vol. 364, Issue 6445, pp. 1030-1031
DOI: 10.1126/science.aax8937

Neurocrine Biosciences to Present Data on Opicapone at the 2019 World Congress on Parkinson’s Disease and Related Disorders

https://www.prnewswire.com/news-releases/neurocrine-biosciences-to-present-data-on-ingrezza-valbenazine-and-opicapone-at-the-2019-world-congress-on-parkinsons-disease-and-related-disorders-300865804.html

Neurocrine Biosciences to Present Data on INGREZZA® (valbenazine) and Opicapone at the 2019 World Congress on Parkinson’s Disease and Related Disorders

– INGREZZA Data from Long-Term Phase III Studies Support Sustained Clinical Benefit, Safety and Tolerability in Patients with Tardive Dyskinesia

– Pooled Analyses of Two Pivotal Studies Showed Opicapone Reduced OFF Time and Was Generally Well Tolerated in More than 500 Patients with Parkinson’s Disease and Motor Fluctuations

Trial of Ursodeoxycholic Acid (UDCA) for Parkinson’s Disease: The “UP” Study

https://clinicaltrials.gov/ct2/show/NCT03840005?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F28%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Trial of Ursodeoxycholic Acid (UDCA) for Parkinson’s Disease: The “UP” Study

DESCRIPTION:
Condition:   Parkinson’s Disease
Intervention:   Drug: Ursonorm
Sponsors:   Sheffield Teaching Hospitals NHS Foundation Trust;   JP Moulton Charitable Foundation;   PRO.MED.CS Praha a.s.;   Clinical Trials Research Unit, University of Sheffield
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03840005

FIRST POSTED:
Fri, 15 Feb 2019 12:00:00 EST

LAST UPDATE POSTED:
06/11/19 06:55AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03840005?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F28%2F2019&lupd_d=14&sort=nwst

Parkinson’s: New gene therapy shows promise for prevention

https://www.medicalnewstoday.com/articles/325407.php

Parkinson’s: New gene therapy shows promise for prevention
Published Today By Maria Cohut Fact checked by Isabel Godfrey
The hallmarks of Parkinson’s disease and some forms of dementia include Lewy bodies, toxic aggregates that form in the brain and disrupt neural circuits. Researchers from Osaka University in Japan are now testing a new preventive therapy in a preliminary mouse study.

Chronic Effects of DBS in Parkinson’s Disease and Dystonia

https://clinicaltrials.gov/ct2/show/NCT01934296?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F22%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Chronic Effects of DBS in Parkinson’s Disease and Dystonia

DESCRIPTION:
Conditions:   Parkinson’s Disease;   Isolated Dystonia
Intervention:   Device: Activa PC+S
Sponsors:   University of California, San Francisco;   Medtronic
Active, not recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT01934296

FIRST POSTED:
Wed, 04 Sep 2013 12:00:00 EDT

LAST UPDATE POSTED:
06/05/19 07:44AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT01934296?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F22%2F2019&lupd_d=14&sort=nwst

BTRX-246040 Study in Subjects With Parkinson’s Disease With Motor Fluctuations [Completed]

https://clinicaltrials.gov/ct2/show/NCT03608371?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F22%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
BTRX-246040 Study in Subjects With Parkinson’s Disease With Motor Fluctuations

DESCRIPTION:
Conditions:   Parkinson Disease;   Motor Disorder
Interventions:   Drug: BTRX-246040;   Drug: Placebo
Sponsor:   BlackThorn Therapeutics, Inc.
Completed

CLINICALTRIALS.GOV IDENTIFIER:
NCT03608371

FIRST POSTED:
Tue, 31 Jul 2018 12:00:00 EDT

LAST UPDATE POSTED:
06/05/19 07:44AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03608371?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F22%2F2019&lupd_d=14&sort=nwst

Study to Evaluate DNL201 in Subjects With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03710707?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F22%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Study to Evaluate DNL201 in Subjects With Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: DNL201 low dose;   Drug: DNL201 high dose;   Drug: Placebo
Sponsor:   Denali Therapeutics Inc.
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03710707

FIRST POSTED:
Thu, 18 Oct 2018 12:00:00 EDT

LAST UPDATE POSTED:
06/05/19 07:44AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03710707?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F22%2F2019&lupd_d=14&sort=nwst

Current Drugs and Potential Future Neuroprotective Compounds for Parkinson’s Disease

https://www.ncbi.nlm.nih.gov/pubmed/30479218?dopt=Abstract

http://www.eurekaselect.com/167781/article

TITLE:
Current Drugs and Potential Future Neuroprotective Compounds for Parkinson’s Disease.

DESCRIPTION:
Related Articles

Current Drugs and Potential Future Neuroprotective Compounds for Parkinson’s Disease.

Curr Neuropharmacol. 2019;17(3):295-306

Authors: Carrera I, Cacabelos R

Abstract

The research progress of understanding the etiology and pathogenesis of Parkinson’s disease (PD) has yet lead to the development of some clinical approaches intended to treat cognitive and behavioral symptoms, such as memory and perception disorders. Despite the major advances in different genetic causes and risk factors for PD, which share common pathways to cell dysfunction and death, there is not yet a complete model of PD that can be used to accurately predict the effect of drugs on disease progression. Clinical trials are also important to test any novel neuro-protective agent, and recently there have been great advances in the use of anti-inflammatory drugs and plant flavonoid antioxidants to protect against specific neuronal degeneration and its interference with lipid and cholesterol metabolism. The increasing knowledge of the molecular events underlying the degenerative process of PD has stimulated research to identify natural compounds capable of halting or slowing the progress of neural deterioration. Polyphenols and flavonoids, which play a neuroprotective role in a wide array of in vitro and in vivo models of neurological disorders, emerged from among the multi-target bio-agents found mainly in plants and microorganisms. This review presents a detailed overview of the multimodal activities of neuroprotective bio-agents tested so far, emphasizing their neurorescue/neuroregenerative activity. The brain-penetrating property of bioagents may make these compounds an important class of natural drugs for the treatment of neurodegenerative diseases. Although there are numerous studies demonstrating beneficial effects in the laboratory by identifying critical molecular targets, the clinical efficacy of these neuroprotective treatments remains to be proven accurately.

PMID: 30479218 [PubMed – indexed for MEDLINE]

PMID:
PubMed:30479218

DATE FOUND:
06/04/19 06:01AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/30479218?dopt=Abstract

Clinical Trial to Evaluate the Safety and Tolerability of Molecular Hydrogen in Patients With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03971617?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F20%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Clinical Trial to Evaluate the Safety and Tolerability of Hydrogen in Patients With Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: Hydrogen;   Drug: Placebo oral tablet
Sponsor:   Stony Brook University
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03971617

FIRST POSTED:
Mon, 03 Jun 2019 12:00:00 EDT

LAST UPDATE POSTED:
06/03/19 07:42AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03971617?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F20%2F2019&lupd_d=14&sort=nwst

Effects of Lingzhi (Ganoderma) on Disease Progression in Patients With Untreated Early Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03594656?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F15%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Effects of Lingzhi on Disease Progression in Patients With Untreated Early Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: Ganoderma;   Drug: Placebos
Sponsor:   Xuanwu Hospital, Beijing
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03594656

FIRST POSTED:
Fri, 20 Jul 2018 12:00:00 EDT

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

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03594656?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F15%2F2019&lupd_d=14&sort=nwst

Focused ultrasound opening of the blood-brain barrier for treatment of Parkinson’s disease

https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27722

https://www.ncbi.nlm.nih.gov/pubmed/31136023?dopt=Abstract

TITLE:
Focused ultrasound opening of the blood-brain barrier for treatment of Parkinson’s disease.

DESCRIPTION:
Focused ultrasound opening of the blood-brain barrier for treatment of Parkinson’s disease.

Mov Disord. 2019 May 28;:

Authors: LeWitt PA, Lipsman N, Kordower JH

Abstract

The expanding landscape of options for Parkinson’s disease (PD) therapeutics calls for novel ways to improve delivery of treatments to counteract neurodegeneration or enhance symptomatic control. This unmet need is particularly relevant for opportunities in gene therapy, which, in recent PD clinical trials, has required invasive neurosurgical approaches into the CNS. One of the promising techniques to bring new therapies into the brain for PD therapeutics involves an evolving technology, focused ultrasound. Focused ultrasound has been used to alleviate tremor by thermal ablation with high-energy sonication. Using similar equipment but much lower sonication energy, focused ultrasound assisted with micro-bubbles can temporarily open the blood-brain barrier at specific brain targets to facilitate real-time magnetic resonance-guided delivery of therapeutic agents. To explore the current status and future of focused ultrasound in transvascular therapeutics for PD, a November 2018 workshop reviewed its accomplishments and challenges. This report summarizes key points of discussion and provides further background to the promising roles focused ultrasound offers. © 2019 International Parkinson and Movement Disorder Society.

PMID: 31136023 [PubMed – as supplied by publisher]

PMID:
PubMed:31136023

DATE FOUND:
05/29/19 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31136023?dopt=Abstract

A Global Study to Assess the Drug Dynamics, Efficacy, and Safety of GZ/SAR402671 in Parkinson’s Disease Patients Carrying a Glucocerebrosidase (GBA) Gene Mutation

https://clinicaltrials.gov/ct2/show/NCT02906020?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F08%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Global Study to Assess the Drug Dynamics, Efficacy, and Safety of GZ/SAR402671 in Parkinson’s Disease Patients Carrying a Glucocerebrosidase (GBA) Gene Mutation

DESCRIPTION:
Condition:   Parkinson’s Disease
Interventions:   Drug: GZ/SAR402671;   Drug: Placebo
Sponsor:   Genzyme, a Sanofi Company
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT02906020

FIRST POSTED:
Mon, 19 Sep 2016 12:00:00 EDT

LAST UPDATE POSTED:
05/22/19 07:42AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT02906020?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F08%2F2019&lupd_d=14&sort=nwst

A Study to Assess the Safety of GRF6021 Infusions in Subjects With Parkinson’s Disease and Cognitive Impairment

https://clinicaltrials.gov/ct2/show/NCT03713957?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F08%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Study to Assess the Safety of GRF6021 Infusions in Subjects With Parkinson’s Disease and Cognitive Impairment

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: GRF6021;   Other: Placebo
Sponsors:   Alkahest, Inc.;   Michael J. Fox Foundation for Parkinson’s Research
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03713957

FIRST POSTED:
Mon, 22 Oct 2018 12:00:00 EDT

LAST UPDATE POSTED:
05/22/19 07:42AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03713957?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F08%2F2019&lupd_d=14&sort=nwst

Modulation of Gut Microbiota by Rifaximin in PD Patients

https://clinicaltrials.gov/ct2/show/NCT03958708?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F08%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Modulation of Gut Microbiota by Rifaximin in PD Patients

DESCRIPTION:
Conditions:   Parkinson Disease;   Inflammation
Intervention:   Drug: Rifaximin 550 MG
Sponsor:   Taipei Medical University Shuang Ho Hospital
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03958708

FIRST POSTED:
Wed, 22 May 2019 12:00:00 EDT

LAST UPDATE POSTED:
05/22/19 07:42AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03958708?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F08%2F2019&lupd_d=14&sort=nwst

Safety and Efficacy of THN102 in Patients With Parkinson’s Disease and Excessive Daytime Sleepiness

https://clinicaltrials.gov/ct2/show/NCT03624920?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F07%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Safety and Efficacy of THN102 in Patients With Parkinson’s Disease and Excessive Daytime Sleepiness

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: THN102 Dosage A;   Drug: THN102 Dosage B;   Drug: THN102 Dosage C
Sponsor:   Theranexus
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03624920

FIRST POSTED:
Fri, 10 Aug 2018 12:00:00 EDT

LAST UPDATE POSTED:
05/21/19 06:55AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03624920?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F07%2F2019&lupd_d=14&sort=nwst

Amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides targeting α-synuclein as a novel therapy for Parkinson’s disease

https://www.nature.com/articles/s41598-019-43772-9

https://www.ncbi.nlm.nih.gov/pubmed/31110191?dopt=Abstract

TITLE:
Amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides targeting α-synuclein as a novel therapy for Parkinson’s disease.

DESCRIPTION:
Related Articles

Amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides targeting α-synuclein as a novel therapy for Parkinson’s disease.

Sci Rep. 2019 May 21;9(1):7567

Authors: Uehara T, Choong CJ, Nakamori M, Hayakawa H, Nishiyama K, Kasahara Y, Baba K, Nagata T, Yokota T, Tsuda H, Obika S, Mochizuki H

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. A characteristic pathological feature of PD is cytoplasmic accumulation of α-synuclein (SNCA) protein. Multiplication of the SNCA gene in familial PD and pathological accumulation of SNCA protein during progression of sporadic PD suggest that increased SNCA protein levels increase the risk of PD. Thus, reducing SNCA expression levels could delay PD onset or modify the disease course. For efficient knock down, we designed and synthesized an amido-bridged nucleic acids (AmNA)-modified antisense oligonucleotide (ASO) that targeted SNCA with improved stability and cellular uptake in vivo. AmNA-ASO efficiently downregulated SNCA at both the mRNA and protein level in vitro and in vivo. Notably, AmNA-ASO was efficiently delivered into the mouse brain by intracerebroventricular injection without the aid of additional chemicals. Furthermore, administration of AmNA-ASO ameliorated neurological defects in PD model mice expressing human wild type SNCA. Taken together, these findings suggest that AmNA-ASO is a promising therapeutic strategy for SNCA-associated pathology in PD.

PMID: 31110191 [PubMed – in process]

PMID:
PubMed:31110191

DATE FOUND:
05/22/19 06:00AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31110191?dopt=Abstract

VY-AADC02 for Parkinson’s Disease With Motor Fluctuations

https://clinicaltrials.gov/ct2/show/NCT03562494?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F06%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
VY-AADC02 for Parkinson’s Disease With Motor Fluctuations

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Biological: VY-AADC02;   Other: Placebo
Sponsors:   Neurocrine Biosciences;   Voyager Therapeutics
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03562494

FIRST POSTED:
Tue, 19 Jun 2018 12:00:00 EDT

LAST UPDATE POSTED:
05/20/19 07:34AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03562494?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F06%2F2019&lupd_d=14&sort=nwst

A Phase 1 Study to Assess the Safety, Tolerability and PK of NPT520-34 in Healthy Subjects

https://clinicaltrials.gov/ct2/show/NCT03954600?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F03%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Phase 1 Study to Assess the Safety, Tolerability and PK of NPT520-34 in Healthy Subjects

DESCRIPTION:
Condition:   Healthy Volunteers
Interventions:   Drug: NPT520-34 (125 mg);   Drug: Placebos (125 mg)
Sponsors:   Neuropore Therapies Inc.;   Celerion
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03954600

FIRST POSTED:
Fri, 17 May 2019 12:00:00 EDT

LAST UPDATE POSTED:
05/17/19 07:09AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03954600?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F03%2F2019&lupd_d=14&sort=nwst

Lysosomal exocytosis is a potential therapeutic target in Parkinson’s and other diseases characterized by the accumulation of a-synuclein

http://www.jneurosci.org/content/early/2019/05/16/JNEUROSCI.3085-18.2019

https://www.ncbi.nlm.nih.gov/pubmed/31097622?dopt=Abstract

TITLE:
Increased lysosomal exocytosis induced by lysosomal Ca2+ channel agonists protects human dopaminergic neurons from α-synuclein toxicity.

DESCRIPTION:
Related Articles

Increased lysosomal exocytosis induced by lysosomal Ca2+ channel agonists protects human dopaminergic neurons from α-synuclein toxicity.

J Neurosci. 2019 May 16;:

Authors: Tsunemi T, Perez-Rosello T, Ishiguro Y, Yoroisaka A, Jeon S, Hamada K, Krishna Vangipuram Suresh M, Wong YC, Xie Z, Akamatsu W, Mazzulli JR, Surmeier DJ, Hattori N, Krainc D

Abstract

The accumulation of misfolded proteins is a common pathological feature of many neurodegenerative disorders, including synucleinopathies such as Parkinson’s disease which is characterized by the presence of α-synuclein (α-syn) containing Lewy bodies. However, while recent studies have investigated α-syn accumulation and propagation in neurons, the molecular mechanisms underlying α-syn transmission have been largely unexplored. Here, we examined a monogenic form of synucleinopathy caused by loss of function mutations in lysosomal ATP13A2/PARK9. These studies revealed that lysosomal exocytosis regulates intracellular levels of α-syn in human neurons. Loss of PARK9 function in patient-derived dopaminergic neurons disrupted lysosomal Ca2+ homeostasis, reduced lysosomal Ca2+ storage, increased cytosolic Ca2+ and impaired lysosomal exocytosis. Importantly, this dysfunction in lysosomal exocytosis impaired α-syn secretion from both axons and soma, promoting α-syn accumulation. However, activation of the lysosomal Ca2+ channel – transient receptor potential mucolipin 1 (TRPML1) – was sufficient to upregulate lysosomal exocytosis, rescue defective α-syn secretion and prevent α-syn accumulation. Together, these results suggest that intracellular α-syn levels are regulated by lysosomal exocytosis in human dopaminergic neurons, and may represent a potential therapeutic target for Parkinson’s disease and other synucleinopathies. Significant Statement: Parkinson’s disease is the second most common neurodegenerative disease linked to the accumulation of a-synuclein in patient neurons. But it is unclear what this mechanism might be. Here, we demonstrate a novel role for lysosomal exocytosis in clearing intracellular a-synuclein, and show that impairment of this pathway by mutations in the Parkinson’s disease-linked gene ATP13A2/PARK9 contributes to a-synuclein accumulation in human dopaminergic neurons. Importantly, upregulating lysosomal exocytosis by increasing lysosomal Ca2+ levels is sufficient to rescue defective a-synuclein secretion and accumulation in patient neurons. These studies identify lysosomal exocytosis as a potential therapeutic target in diseases characterized by the accumulation of a-synuclein including Parkinson’s disease.

PMID: 31097622 [PubMed – as supplied by publisher]

PMID:
PubMed:31097622

DATE FOUND:
05/18/19 06:00AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31097622?dopt=Abstract

A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson’s Disease Patients With Motor Fluctuations

https://clinicaltrials.gov/ct2/show/NCT03670953?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F02%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Study to Evaluate the Safety and Efficacy of IPX203 in Parkinson’s Disease Patients With Motor Fluctuations

DESCRIPTION:
Condition:   Parkinson’s Disease (Disorder)
Interventions:   Drug: IR CD-LD;   Drug: IPX203 ER CD-LD;   Other: IPX203 placebo;   Other: IR CD-LD placebo
Sponsor:   IMPAX Laboratories, Inc.
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03670953

FIRST POSTED:
Fri, 14 Sep 2018 12:00:00 EDT

LAST UPDATE POSTED:
05/16/19 07:19AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03670953?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F02%2F2019&lupd_d=14&sort=nwst

Targeting kinases in Parkinson’s disease: A mechanism shared by LRRK2, neurotrophins, exenatide, urate, nilotinib and lithium

https://www.jns-journal.com/article/S0022-510X(19)30232-1/fulltext

https://www.ncbi.nlm.nih.gov/pubmed/31129265?dopt=Abstract

TITLE:
Targeting kinases in Parkinson’s disease: A mechanism shared by LRRK2, neurotrophins, exenatide, urate, nilotinib and lithium.

DESCRIPTION:
Related Articles

Targeting kinases in Parkinson’s disease: A mechanism shared by LRRK2, neurotrophins, exenatide, urate, nilotinib and lithium.

J Neurol Sci. 2019 May 15;402:121-130

Authors: Guttuso T, Andrzejewski KL, Lichter DG, Andersen JK

Abstract

Several kinases have been implicated in the pathogenesis of Parkinson’s disease (PD), most notably leucine-rich repeat kinase 2 (LRRK2), as LRRK2 mutations are the most common genetic cause of a late-onset parkinsonism that is clinically indistinguishable from sporadic PD. More recently, several other kinases have emerged as promising disease-modifying targets in PD based on both preclinical studies and clinical reports on exenatide, the urate precursor inosine, nilotinib and lithium use in PD patients. These kinases include protein kinase B (Akt), glycogen synthase kinases-3β and -3α (GSK-3β and GSK-3α), c-Abelson kinase (c-Abl) and cyclin-dependent kinase 5 (cdk5). Activities of each of these kinases are involved either directly or indirectly in phosphorylating tau or increasing α-synuclein levels, intracellular proteins whose toxic oligomeric forms are strongly implicated in the pathogenesis of PD. GSK-3β, GSK-3α and cdk5 are the principle kinases involved in phosphorylating tau at sites critical for the formation of tau oligomers. Exenatide analogues, urate, nilotinib and lithium have been shown to affect one or more of the above kinases, actions that can decrease the formation and increase the clearance of intraneuronal phosphorylated tau and α-synuclein. Here we review the current preclinical and clinical evidence supporting kinase-targeting agents as potential disease-modifying therapies for PD patients enriched with these therapeutic targets and incorporate LRRK2 physiology into this novel model.

PMID: 31129265 [PubMed – as supplied by publisher]

PMID:
PubMed:31129265

DATE FOUND:
05/28/19 01:23PM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31129265?dopt=Abstract

A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Japanese Participants With Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03716570?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F01%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Japanese Participants With Parkinson’s Disease

DESCRIPTION:
Condition:   Parkinson’s Disease
Interventions:   Drug: BIIB054;   Drug: Placebo
Sponsor:   Biogen
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03716570

FIRST POSTED:
Tue, 23 Oct 2018 12:00:00 EDT

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

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03716570?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=05%2F01%2F2019&lupd_d=14&sort=nwst

Single Ascending Dose Study of MEDI1341 in Healthy Volunteers

https://clinicaltrials.gov/ct2/show/NCT03272165?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=04%2F29%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Single Ascending Dose Study of MEDI1341 in Healthy Volunteers

DESCRIPTION:
Condition:   Parkinson’s Disease
Interventions:   Drug: MEDI1341;   Drug: Placebo
Sponsors:   AstraZeneca;   Covance;   MMS Holdings, Inc;   Catalent
Recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03272165

FIRST POSTED:
Tue, 05 Sep 2017 12:00:00 EDT

LAST UPDATE POSTED:
05/13/19 07:43AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03272165?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=04%2F29%2F2019&lupd_d=14&sort=nwst

Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5HT2A Inverse Agonist, to Treat Impulse Control Disorders in Parkinson’s Disease

https://clinicaltrials.gov/ct2/show/NCT03947216?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=04%2F29%2F2019&lupd_d=14&sort=nwst

STUDY TITLE:
Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5HT2A Inverse Agonist, to Treat Impulse Control Disorders in Parkinson’s Disease.

DESCRIPTION:
Condition:   Parkinson Disease
Interventions:   Drug: Active drug: pimavanserin 17mg (2 strength tablets);   Drug: Placebo: 2 tablets containing same excipients except active compound;   Behavioral: Assessment of severity of ICD (impulse control disorders);   Behavioral: Assessment of motor and non-motors symptoms of PD Evaluation of hyper- and hypodopaminergic behaviors;   Behavioral: Assessment of quality of life;   Behavioral: Assessment of depression;   Behavioral: Assessment of cognition;   Behavioral: Assessment of severity of Parkinson Disease;   Procedure: Blood analysis;   Procedure: Cardiac monitoring
Sponsor:   University Hospital, Strasbourg, France
Not yet recruiting

CLINICALTRIALS.GOV IDENTIFIER:
NCT03947216

FIRST POSTED:
Mon, 13 May 2019 12:00:00 EDT

LAST UPDATE POSTED:
05/13/19 07:43AM

STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03947216?recrs=abdef&type=Intr&cond=Parkinson+Disease&phase=0124&lupd_s=04%2F29%2F2019&lupd_d=14&sort=nwst

PDZ Scaffold Protein CAL Couples with Metabotropic Glutamate Receptor 5 to Protect Against Cell Apoptosis and Is a Potential Target in the Treatment of Parkinson’s Disease

https://link.springer.com/article/10.1007%2Fs13311-019-00730-7

https://www.ncbi.nlm.nih.gov/pubmed/31073978

PDZ Scaffold Protein CAL Couples with Metabotropic Glutamate Receptor 5 to Protect Against Cell Apoptosis and Is a Potential Target in the Treatment of Parkinson’s Disease

Abstract
Targeting mGluR5 has been an attractive strategy to modulate glutamate excitotoxicity for neuroprotection. Although human clinical trials using mGluR5 negative allosteric modulators (NAMs) have included some disappointments, recent investigations have added several more attractive small molecules to this field, providing a promise that the identification of more additional strategies to modulate mGluR5 activity might be potentially beneficial for the advancement of PD treatment. Here, we determined the role of the interacting partner CAL (cystic fibrosis transmembrane conductance regulator-associated ligand) in mGluR5-mediated protection in vitro and in vivo. In astroglial C6 cells, CAL deficiency blocked (S)-3, 5-dihydroxyphenylglycine (DHPG)-elicited p-AKT and p-ERK1/2, subsequently prevented group I mGluRs-mediated anti-apoptotic protection, which was blocked by receptor antagonist 1-aminoindan-1, 5-dicarboxylic acid (AIDA), and PI3K or MEK inhibitor LY294002 or U0126. In rotenone-treated MN9D cells, both CAL and mGluR5 expressions were decreased in a time- and dose-dependent manner, and the correlation between these 2 proteins was confirmed by lentivirus-delivered CAL overexpression and knockdown. Moreover, CAL coupled with mGluR5 upregulated mGluR5 protein expression by inhibition of ubiquitin-proteasome-dependent degradation to suppress mGluR5-mediated p-JNK and to protect against cell apoptosis. Additionally, CAL also inhibited rotenone-induced glutamate release to modulate mGluR5 activity. Furthermore, in the rotenone-induced rat model of PD, AAV-delivered CAL overexpression attenuated behavioral deficits and dopaminergic neuronal death, while CAL deficiency aggravated rotenone toxicity. On the other hand, the protective effect of the mGluR5 antagonist MPEP was weakened by knocking down CAL. In vivo experiments also confirmed that CAL inhibited ubiquitination-proteasome-dependent degradation to modulate mGluR5 expression and JNK phosphorylation. Our findings show that CAL protects against cell apoptosis via modulating mGluR5 activity, and may be a new molecular target for an effective therapeutic strategy for PD.

Neurotherapeutics. 2019 May 9. doi: 10.1007/s13311-019-00730-7. [Epub ahead of print]

First Online: 09 May 2019

FTY720 may reduce Parkinson’s disease progression by inhibiting NLRP3 inflammasome activation

https://www.ncbi.nlm.nih.gov/pubmed/31069623?dopt=Abstract

TITLE:
FTY720 Inhibits MPP+-Induced Microglial Activation by Affecting NLRP3 Inflammasome Activation.

DESCRIPTION:
Related Articles

FTY720 Inhibits MPP+-Induced Microglial Activation by Affecting NLRP3 Inflammasome Activation.

J Neuroimmune Pharmacol. 2019 May 08;:

Authors: Yao S, Li L, Sun X, Hua J, Zhang K, Hao L, Liu L, Shi D, Zhou H

Abstract

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons and excessive microglial activation in the substantia nigra pars compacta (SNpc). In the present study, we aimed to demonstrate the therapeutic effectiveness of the potent sphingosine-1-phosphate receptor antagonist fingolimod (FTY720) in an animal model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and to identify the potential mechanisms underlying these therapeutic effects. C57BL/6J mice were orally administered FTY720 before subcutaneous injection of MPTP. Open-field and rotarod tests were performed to determine the therapeutic effect of FTY720. The damage to dopaminergic neurons and the production of monoamine neurotransmitters were assessed using immunohistochemistry, high-performance liquid chromatography, and flow cytometry. Immunofluorescence (CD68- positive) and enzyme-linked immunosorbent assay were used to analyze the activation of microglia, and the levels of activated signaling molecules were measured using Western blotting. Our findings indicated that FTY720 significantly attenuated MPTP-induced behavioral deficits, reduced the loss of dopaminergic neurons, and increased dopamine release. FTY720 directly inhibited MPTP-induced microglial activation in the SNpc, suppressed the production of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in BV-2 microglial cells treated with 1-methyl-4-phenylpyridinium (MPP+), and subsequently decreased apoptosis in SH-SY5Y neuroblastoma cells. Moreover, in MPP+-treated BV-2 cells and primary microglia, FTY720 treatment significantly attenuated the increases in the phosphorylation of PI3K/AKT/GSK-3β, reduced ROS generation and p65 activation, and also inhibited the activation of NLRP3 inflammasome and caspase-1. In conclusion, FTY720 may reduce PD progression by inhibiting NLRP3 inflammasome activation via its effects on ROS generation and p65 activation in microglia. These findings provide novel insights into the mechanisms underlying the therapeutic effects of FTY720, suggesting its potential as a novel therapeutic strategy against PD. Graphical Abstract FTY720 may reduce ROS production by inhibiting the PI3K/AKT/GSK-3β signaling pathway, while at the same time reducing p65 phosphorylation, thus decreasing NLRP3 inflammasome activation through these two pathways, ultimately reducing microglia activation-induced neuronal damage.

PMID: 31069623 [PubMed – as supplied by publisher]

PMID:
PubMed:31069623

DATE FOUND:
05/11/19 12:52PM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31069623?dopt=Abstract

Evaluating ADS5102 (amantadine) for the treatment of Parkinson’s disease patients with dyskinesia

https://www.ncbi.nlm.nih.gov/pubmed/31058557?dopt=Abstract

TITLE:
Evaluating ADS5102 (amantadine) for the treatment of Parkinson’s disease patients with dyskinesia.

DESCRIPTION:
Related Articles

Evaluating ADS5102 (amantadine) for the treatment of Parkinson’s disease patients with dyskinesia.

Expert Opin Pharmacother. 2019 May 06;:1-7

Authors: Müller T, Kuhn W, Möhr JD

Abstract

INTRODUCTION: Amantadine is an old, antiviral compound that moderately ameliorates impaired motor behaviour in Parkinson’s disease. Its current resurgence results from the novel retarded release amantadine hydrochloride formulation, ADS5102, which has also received approval for the treatment of levodopa-related involuntary movements known as dyskinesia. Areas covered: This non-systematic, narrative drug evaluation discusses the value of ADS5102 for patients with Parkinson’s disease. ADS5102 is orally applied once daily in the evening. This capsule provides higher and more continuous amantadine plasma concentrations than conventional amantadine immediate release formulations with their two to three times daily intake plan. Expert opinion: ADS5102 was superior to placebo in clinical trials. They aimed for the amelioration of motor complications, particularly at ‘OFF’ periods and with dyskinesia in fluctuating levodopa treated patients with Parkinson’s disease. Side effects and tolerability were similar to the well-known effects of conventional amantadine formulations. ADS5102 simplifies treatment and improves compliance problems in the long run. The marketing of ADS5102 outside the US will be complex for return of research costs and investments required for its manufacturing. Indeed, worldwide institutional price regulation scenarios often only consider new therapeutic mode of actions as being innovative as opposed to old drugs with improved pharmacokinetic behaviour.

PMID: 31058557 [PubMed – as supplied by publisher]

PMID:
PubMed:31058557

DATE FOUND:
05/11/19 12:46PM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31058557?dopt=Abstract
https://www.tandfonline.com/doi/abs/10.1080/14656566.2019.1612365?journalCode=ieop20

Neurocrine Biosciences Presents Phase III Data Analysis Demonstrating that Opicapone Added to Levodopa Resulted in a Significant and Sustained Increase in ON Time without Troublesome Dyskinesia in Parkinson’s Disease Patients

https://www.biospace.com/article/neurocrine-biosciences-presents-phase-iii-data-analysis-demonstrating-that-opicapone-added-to-levodopa-resulted-in-a-significant-and-sustained-increase-in-on-time-without-troublesome-dyskinesia-in-parkinson-s-disease-patients/

Neurocrine Biosciences Presents Phase III Data Analysis Demonstrating that Opicapone Added to Levodopa Resulted in a Significant and Sustained Increase in ON Time without Troublesome Dyskinesia in Parkinson’s Disease Patients

Parkinson’s results beyond researchers’ wildest dreams

https://www.bbc.com/news/health-47803496

Parkinson’s results beyond researchers’ wildest dreams

A treatment that has restored the movement of patients with chronic Parkinson’s disease has been developed by Canadian researchers.

Marine-Derived Natural Compounds for the Treatment of Parkinson’s Disease

https://www.mdpi.com/1660-3397/17/4/221/htm

https://www.ncbi.nlm.nih.gov/pubmed/30978965?dopt=Abstract

TITLE:
Marine-Derived Natural Compounds for the Treatment of Parkinson’s Disease.

DESCRIPTION:
Related Articles

Marine-Derived Natural Compounds for the Treatment of Parkinson’s Disease.

Mar Drugs. 2019 Apr 11;17(4):

Authors: Huang C, Zhang Z, Cui W

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons, leading to the motor dysfunctions of patients. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progress was revealed to be associated with the abnormal aggregation of α-synuclein, the elevation of oxidative stress, the dysfunction of mitochondrial functions, and the increase of neuroinflammation. However, current anti-PD therapies could only produce symptom-relieving effects, because they could not provide neuroprotective effects, stop or delay the degeneration of dopaminergic neurons. Marine-derived natural compounds, with their novel chemical structures and unique biological activities, may provide anti-PD neuroprotective effects. In this study, we have summarized anti-PD marine-derived natural products which have shown pharmacological activities by acting on various PD targets, such as α-synuclein, monoamine oxidase B, and reactive oxygen species. Moreover, marine-derived natural compounds currently evaluated in the clinical trials for the treatment of PD are also discussed.

PMID: 30978965 [PubMed – indexed for MEDLINE]

PMID:
PubMed:30978965

DATE FOUND:
09/04/19 06:02AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/30978965?dopt=Abstract

Small Trial Provides New Hope Against Parkinson’s Disease

https://www.usnews.com/news/health-news/articles/2019-03-01/small-trial-provides-new-hope-against-parkinsons-disease

https://consumer.healthday.com/cognitive-health-information-26/parkinson-s-news-526/small-trial-provides-new-hope-against-parkinson-s-disease-743154.html

Histamine N-Methyltransferase in the Brain

https://www.mdpi.com/1422-0067/20/3/737

https://www.ncbi.nlm.nih.gov/pubmed/30744146?dopt=Abstract

TITLE:
Histamine N-Methyltransferase in the Brain.

DESCRIPTION:
Related Articles

Histamine N-Methyltransferase in the Brain.

Int J Mol Sci. 2019 Feb 10;20(3):

Authors: Yoshikawa T, Nakamura T, Yanai K

Abstract

Brain histamine is a neurotransmitter and regulates diverse physiological functions. Previous studies have shown the involvement of histamine depletion in several neurological disorders, indicating the importance of drug development targeting the brain histamine system. Histamine N-methyltransferase (HNMT) is a histamine-metabolising enzyme expressed in the brain. Although pharmacological studies using HNMT inhibitors have been conducted to reveal the direct involvement of HNMT in brain functions, HNMT inhibitors with high specificity and sufficient blood⁻brain barrier permeability have not been available until now. Recently, we have phenotyped Hnmt-deficient mice to elucidate the importance of HNMT in the central nervous system. Hnmt disruption resulted in a robust increase in brain histamine concentration, demonstrating the essential role of HNMT in the brain histamine system. Clinical studies have suggested that single nucleotide polymorphisms of the human HNMT gene are associated with several brain disorders such as Parkinson’s disease and attention deficit hyperactivity disorder. Postmortem studies also have indicated that HNMT expression is altered in human brain diseases. These findings emphasise that an increase in brain histamine levels by novel HNMT inhibitors could contribute to the improvement of brain disorders.

PMID: 30744146 [PubMed – indexed for MEDLINE]

PMID:
PubMed:30744146

DATE FOUND:
05/30/19 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/30744146?dopt=Abstract

The Potential of L-Type Calcium Channels as a Drug Target for Neuroprotective Therapy in Parkinson’s Disease

https://www.annualreviews.org/doi/10.1146/annurev-pharmtox-010818-021214

https://www.ncbi.nlm.nih.gov/pubmed/30625283?dopt=Abstract

TITLE:
The Potential of L-Type Calcium Channels as a Drug Target for Neuroprotective Therapy in Parkinson’s Disease.

DESCRIPTION:
Related Articles

The Potential of L-Type Calcium Channels as a Drug Target for Neuroprotective Therapy in Parkinson’s Disease.

Annu Rev Pharmacol Toxicol. 2019 01 06;59:263-289

Authors: Liss B, Striessnig J

Abstract

The motor symptoms of Parkinson’s disease (PD) mainly arise from degeneration of dopamine neurons within the substantia nigra. As no disease-modifying PD therapies are available, and side effects limit long-term benefits of current symptomatic therapies, novel treatment approaches are needed. The ongoing phase III clinical study STEADY-PD is investigating the potential of the dihydropyridine isradipine, an L-type Ca2+ channel (LTCC) blocker, for neuroprotective PD therapy. Here we review the clinical and preclinical rationale for this trial and discuss potential reasons for the ambiguous outcomes of in vivo animal model studies that address PD-protective dihydropyridine effects. We summarize current views about the roles of Cav1.2 and Cav1.3 LTCC isoforms for substantia nigra neuron function, and their high vulnerability to degenerative stressors, and for PD pathophysiology. We discuss different dihydropyridine sensitivities of LTCC isoforms in view of their potential as drug targets for PD neuroprotection, and we conclude by considering how these aspects could guide further drug development.

PMID: 30625283 [PubMed – indexed for MEDLINE]

PMID:
PubMed:30625283

DATE FOUND:
05/15/20 06:00AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/30625283?dopt=Abstract

Parkinson’s Forum UK

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https://forum.parkinsons.org.uk/categories
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