The Road Ahead for Possible Parkinson's Antibody PRX002

JUNE 07, 2017
Kevin Kunzmann
While attending the 21st International Congress of Parkinson's Disease and Movement Disorders, Anthony Lang (pictured), MD, FRCPC, shared insight on an exciting investigative treatment for Parkinson's disease (PD) that, while still early into trial, has shown promising efficacy.

PRX002 is an antibody capable of accessing the central nervous system (CNS) and managing toxic protein alpha-synuclein — a prominent mark in PD patients. Though its Phase II-B trial for safety and tolerability just recently reported positive results, Lang believes its time for the next step toward clinical trial.

Lang, professor and director for the Department of Neurology at the University of Toronto, and a former president of the International Parkinson and Movement Disorder Society, detailed the background and road ahead for possible PRX002 treatmen for PD.

Lang: I think our understanding of the pathogenesis of Parkinsnon’s disease (PD) continues to advance and expand. So does our understanding of how different genes play roles, and the pathways influence the way cells handle toxic proteins — particularly alpha-synuclein — and how different genes interact with one another in doing that.
 
The area that has been hot for some time is a recognition that there is a potential for these toxic proteins — alpha-synuclein — in Parkinson’s. There’s interest in how they transmit from one cell to another, and therefore there is a wide recognition of an extracellular of these toxic proteins. We hope we can interact with that abnormal protein at times when the protein may be extracellular.

There’s obviously an interest in doing things at multiple levels, and entering cells as well, but with this extracellular phase there is potential to use therapies that don’t necessarily have to have an access into neurons, which makes certain types of treatments more challenging. In the case of these toxic proteins, there is a lot of interest in the potential for vaccines. Most of the activity now is in using passive immunization with antibodies directed at the proteins.
 
This has been used in Alzheimer’s disease, and Alzheimer’s research is probably well-advanced when compared to Parkinson’s or any of the other neurodegenerative disorders. We’ve learned certain lessons in Alzheimer’s disease, and I think more research trials have become more promising, knowing what we’ve learned from the initial phases.
 
In the case of Parkinson’s, there are companies developing antibodies — monoclonal antibodies directed at the alpha-synuclein, or different components of the alpha-synuclein. And one of the reports coming from the congress here is a study using an antibody called PRX002. This is a Phase II-B trial in patients with early to moderate Parkinson’s disease. This Phase II trial doesn’t show efficacy, it is showing safety and tolerability. And it show important and promising results in terms of what you would hope to predict for in efficacy.
 
Safety was shown, there were no significant treatment-related adverse effects. There were adverse effects, including one allergic reaction, but these were all reversible and patients recovered well.
 
They showed the treatment got into the cerebral spinal fluid, so that’s very important. Obviously, you want your treatment to cross into the brain. They were able to measure the antibodies that managed to cross over into the cerebral spinal fluid at a low level, but an important level.
 
They also showed there was a dose-related reduction in the protein in the serum. You want that antibody to be interacting with the protein, so they were able to show a very, very significant reduction in protein in the serum — down to about 97%.
 
It seems, at least in the small studies done to be safe, the antibody gets into the brain and the spinal fluid and interacts with the alpha-synuclein protein in a way we would hope it will. I think that’s all very promising and exciting, and it indicates we’re getting to a point where this kind of treatment can move into Phase II trials with the hope we’re going to see change in the course of the disease. So it’s all very exciting.
 

Copyright© MD Magazine 2006-2017 Intellisphere, LLC. All Rights Reserved.