Researchers, Advocates Collaborate for In-depth Review of Clinical Trials Targeting Parkinson’s

A considerable amount of effort is being put into finding therapeutic agents for Parkinson’s disease, with several symptomatic and disease-modifying therapies currently being evaluated in clinical trials, according to a recent comprehensive review.

The review, “Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2020,” was published in the Journal of Parkinson’s Disease. 

With the incidence of Parkinson’s increasing and the global number of cases expected to double by 2040, a team of researchers and research advocates working with the Cure Parkinson’s Trust and their collaborators, conducted a review of all pharmacological therapies currently under investigation.

The researchers said the objective of their study was to create “greater awareness and opportunities for collaboration amongst commercial and academic researchers as well as between the research and patient communities.”

Using the database clinicaltrials.gov, and excluding observational and non-drug related studies, the team identified 145 registered and ongoing trials of potential therapeutic agents that were active as of Jan. 21.

Trials were allocated into a total of 14 categories, including:

• dopaminergic symptom relief therapies (symptomatic therapies that either restore, replace or mimic dopamine, the brain chemical that is gradually lost in Parkinson’s);
• non-dopaminergic symptom relief therapies (symptomatic therapies that affect neurotransmitters other than dopamine);
• antioxidants (agents that can lower oxidative stress, or cell damage as a consequence of high levels of oxidant molecules);
• cell therapy;
• immunotherapy;
• microbiome (where agents target the activity of the gastrointestinal system);
• those targeting alpha synuclein.

Among these trials, 51 (35%) were in Phase 1 testing, 66 (46%) in Phase 2, and 28 (19%) in Phase 3. Of these, 57 trials (39%) focused on long-term disease modifying therapies, while the remaining 88 trials (61%) investigated short-term therapies geared toward daily symptomatic relief.

Fifty trials (34%) are investigating repurposed therapies, or those that were originally developed for other conditions. Drug repurposing — also known as drug repositioning — represents a potentially faster way to find new treatments, since the compounds under investigation already have been approved.

“The number of clinical trials under way is encouraging for the Parkinson’s community, especially the high proportion of repurposed initiatives that increase the chances of a new therapy becoming available more quickly,” said Kevin McFarthing, PhD, in a press release for the Cure Parkinson’s Trust. McFarthing is the review’s first author and a Parkinson’s research advocate.

Of the 88 trials that were investigating symptomatic therapies, 58 were focused on motor symptoms, including overall movement (45 trials), levodopa-induced dyskinesia (involuntary muscle movements, six trials), gait and balance (four trials) and tremor (three trials).

Among the trials testing for disease-modifying therapies, four studies focused on mitochondrial deficiencies. Mitochondria, the cells’ powerhouses, have been implicated in the development of Parkinson’s disease. These included trials investigating ursodeoxycholic acid, PTC Therapeutics‘ EPI-589 and Clene Nanomedicine‘s CNM Au8 (gold nanocrystals).

Four studies focused on the activity of the GBA gene (which provides instructions for making an enzyme called glucocerebrosidase) and whose mutations significantly increase the risk of Parkinson’s. These included Sanofi‘s venglustat, Prevail Therapeutics‘ PR001 gene therapy, and studies repurposing the respiratory medication ambroxol.

Importantly, the authors noted that adding to the 145 trials found in their analysis, were more than 40 trials investigating specific biomarkers for Parkinson’s disease.

This is important as “[t]he lack of accurate and reliable biomarkers for PD [Parkinson’s disease] causes great difficulty in early diagnosis, as well as in measuring disease progression. Better biomarkers may also allow for shorter and more efficient clinical trials” the researchers wrote.

“With the discovery of the first genetic risk factors for PD at the turn of this century, researchers have begun to develop a better understanding of the possible biological pathways that may be governing/influencing the progressive neurodegeneration associated with PD,” study author Simon Stott, PhD, deputy director of research, The Cure Parkinson’s Trust, said in a press release.

“These discoveries have led to a growing number of clinical trials targeting an increasing number of potentially disease-relevant mechanisms of action. It is important for the research and Parkinson’s communities to stay abreast of the extensive, ever-changing landscape in order to highlight trends and better manage expectations,” Stott said.