Vaccine for Parkinson’s Reports Postive Results
Monday, 12th September 2016

New study results from Austrian biotech AFFiRiS support continued development of its vaccine against the key Parkinson’s protein alpha-synuclein. Today the company announced its “boost” follow-up study — funded with a $1.04 million grant from The Michael J. Fox Foundation — showed that an additional dose is safe and can elicit antibodies against alpha-synuclein. AFFiRiS will present a poster on the study at the World Parkinson Congress in Portland, Oregon on Wednesday, September 21.

Researchers believe that clumps of this protein (also called fibrils) are toxic and cause the cell death that leads to Parkinson’s disease (PD) symptoms and progression.

AFFiRiS has developed a vaccine (called PD01A) to cause the body’s immune system to create antibodies against alpha-synuclein, hopefully clearing out the clumps and protecting cells. The treatment works much like the flu vaccine, activating the body to create its own natural disease fighters.

The “boost” study builds on a first clinical trial, also funded by MJFF, where 24 participants with early-stage Parkinson’s received four doses of PD01A. That trial proved the treatment was safe and showed that half of the participants created alpha-synuclein antibodies. Within a year, however, each of the “responders” saw their levels of alpha-synuclein antibodies decline.

This follow-up trial gave each participant one more dose a year later to see if a “boost” would be safe and would raise antibody levels again. AFFiRiS reported today that the trial was safe; all 28 participants (22 from the first trial and six other people with PD) completed the study. In addition, more volunteers (86 percent) saw an antibody response. All responders from the first trial responded again, and some who did not respond in the first trial produced antibodies with the boost.

“This showed that the body is not desensitized to the vaccine and can produce alpha-synuclein antibodies again,” said Kuldip Dave, PhD, MJFF director of research programs who directs our alpha-synuclein portfolio. “And that you don’t have only one opportunity for treatment — that if you don’t produce antibodies with a first round of vaccine, you may with follow-up.”

Many questions remain about this therapy:

What about those 14% who didn’t respond with antibodies in this trial? Dr. Dave says he’s not surprised to see that not everyone responded because the treatment is relying on each person’s immune system to create the antibodies and we just don’t know enough about the protein or those individuals’ Parkinson’s or other biology. Future trials may explore those non-responders to determine who would be a good candidate for a therapy such as PD01A.

Would the antibodies work against the type of alpha-synuclein that causes Parkinson’s? Researchers don’t know yet, but laboratory tests showed that PD01A-induced antibodies did bind to alpha-synuclein fibrils, the type thought to be toxic and associated with PD.

Can they keep the antibody levels up? That’s the next step. A second follow-up study (“reboost”) is ongoing, funded by MJFF, to monitor the participants and give another dose when their antibody levels start to fall.

Will PD01A slow or stop Parkinson’s disease? The big question. Trials are still in the safety phase and not designed to test efficacy (there is no placebo, for example), but some preliminary observations are promising. Many (42 percent) of antibody responders from the first trial did not need to increase their dopamine medication over the study observation period (an average of three years). Future studies will be designed to assess efficacy.

In parallel, MJFF is leading efforts to validate measures of alpha-synuclein in living people so we can quickly and confidently assess the impact of therapies such as PD01A. Programs such as our Parkinson’s Progression Markers Initiative and Alpha-synuclein Imaging Consortium are working toward such tools.

Source: The Michael J. Fox Foundation for Parkinson’s research