One of the most promising approaches to stopping Parkinson's is to target the rogue protein alpha-synuclein. Six clinical trials are testing therapies with this goal.

In Parkinson's, alpha-synuclein clumps together to form aggregates called Lewy bodies, which scientists believe are toxic and lead to disease symptoms and progression. If researchers can prevent the protein from clumping into Lewy bodies, clear them out or stop their spread from cell to cell, they may stop Parkinson's disease (PD).

The Michael J. Fox Foundation has helped advance the development of therapies with that goal, directly funding some of the six projects now in human testing and providing resources to help design others. Here we share the latest updates from the field of alpha-synuclein clinical trials.

Introducing Antibodies against Alpha-Synuclein

• One way scientists are going after alpha-synuclein is with antibodies: the body's immune system fighters. Biotechnology company Prothena is partnering with Roche to test its antibody (PRX002/RO7046015) against alpha-synuclein in people recently diagnosed with PD. Last month scientists published that the companies' antibody was safe in a Phase I trial in people with PD and lowered levels of alpha-synuclein in blood samples. The Phase II trial (called PASADENA) is taking place in Austria, France, Germany, Spain and the United States. Learn more on the study's website and see a list of recruiting sites on MJFF's trial matching site Fox Trial Finder.
   
• Biogen is also testing an anti-alpha-synuclein antibody in people with Parkinson's in a Phase II trial (called the SPARK study). Enrollment is on hold for a short time while the company analyzes data from the first part of the trial. This hiatus was pre-planned to assess safety and understand how different doses work in the body. Stay tuned to our blog to hear when the Biogen trial is accepting new participants, and learn more about its eligibility criteria on the study website. You can also connect with your local study site on Fox Trial Finder.
   
• AstraZeneca and Takeda are together testing an alpha-synuclein antibody in control volunteers at a single site in Dallas, Texas. Learn more and get contact information for the trial team.

Harnessing the Power of the Immune System to Protect Cells

• Austrian biotech AFFiRiS found its vaccine, which prompts the body to produce alpha-synuclein antibodies (like the flu vaccine does against influenza), was safe and tolerable in a series of Phase I trials funded by MJFF. The studies tested six doses over four years, and scientists saw an immune response. "Clinical scores for PD were stable during the entire study period, however, the study was not designed and not powered to evaluate clinical efficacy," wrote the company in a press release. AFFiRiS is planning a Phase II trial to investigate the vaccine's efficacy.

Preventing Toxic Protein Clumps

• MJFF-grantee Neuropore partnered with pharma company UCB to develop the NPT200-11/ UCB0599 compound, which binds to alpha-synuclein and blocks its accumulation. UCB is now planning a Phase Ib study to look for safety and tolerability in both control volunteers and people with Parkinson's at a single study site in Europe.
   
• Proclara (formerly Neurophage) is developing NPT088, which can bind to proteins including alpha-synuclein, amyloid-beta and tau. (The latter two are implicated in Alzheimer's disease and frontotemporal dementia.) MJFF funding helped show NPT088 reduces protein aggregation in a PD model. Proclara is conducting a Phase I trial in people with Alzheimer's because there is a tool to visualize amyloid-beta protein in the brain, which will help assess how well NPT088 works. MJFF has prioritized the development of a similar imaging agent for alpha-synuclein. If that study is successful, Proclara will test NPT088 in people with Parkinson's. Learn more about the Alzheimer's trial.

These six therapeutics are forging ahead and even more are close on their heels and preparing for testing in human volunteers.

Questions about participating in clinical research? View our Trial Participant Pack for videos and a guidebook to learn more about the process and impact of enrolling in studies.