Parkinson's Vaccine Looks Promising

The first vaccine being developed for Parkinson's disease (PD) is showing early promise.

A phase 1 pilot trial of subcutaneous injections of PD01A, carried out at a single center in Vienna, Austria, shows that the vaccine was well tolerated and safe, that it induced an immune response, and that the immune response appeared to be improving function.

"If you add all this together, I think we have the first evidence that would tell us that these findings are compatible with what we look for with disease modification," Achim Schneeberger, MD, chief medical officer of AFFiRiS, the Austrian pharmaceutical company developing the drug, told a press conference where the top-line results were released.

The vaccine targets alpha-synuclein, a protein that is highly expressed in the brain and that tends to aggregate in patients with PD. It is thought that this process either interferes with normal alpha-synuclein function or is itself toxic to cells. PD01A is designed to stimulate the body to produce antibodies that bind to and clear excess alpha-synuclein.

Because the vaccine is intended to prevent PD, it is important to identify the disease as early as possible. Researchers are looking at markers such as loss of sense of smell, sleep disorders, and other signs that might predate the onset of PD, said Todd Sherer, PhD, chief executive officer of the Michael J. Fox Foundation, which provided $1.5 million in funding for the study.

"There is an ongoing effort to see not only if we can improve the diagnosis of PD and the tracking of PD, but if we can identify people prior to the diagnosis of the disease with the hope that ultimately you'd be able to apply a preventive therapy."

Typical PD

The new study included 32 male and female patients aged 45 to 65 years (mean age, about 55 years), all white, who had been diagnosed with PD during the previous 4 years and who were receiving stable doses of PD medications (eg, levodopa).

Patients included in the trial were "typical of early PD," said Dr. Schneeberger. They were randomly assigned to receive 4 monthly injections of 15 μg (n = 12) or 75 μg (n = 12) of the vaccine or to a control group (n = 8) that continued to get regular PD-related medical care.

The groups were well balanced in terms of baseline functional status. There were no dropouts during the 52-week study; the completion rate was 100%. All patients received all vaccinations as planned.

An independent data safety monitoring board assessed safety and tolerability. There were 235 adverse events (AEs), all of which were mild to moderate and were equally distributed between study groups. The most frequent AE was a local reaction that typically lasted 2 to 4 days. The 3 serious AEs (SAEs) were all judged not related to the vaccine.

"We clearly see that there is no safety signal for PD01A in this phase 1 study," said Dr. Schneeberger.

The study also showed "clearly" that the injections induced antibodies directed toward vaccine components, said Dr. Schneeberger. "Both groups developed a specific immune response."

Fifteen of the 24 patients who were immunized had alpha-synuclein reactivity.

Importantly, these antibodies were found in the cerebrospinal fluid of patients. "In total, we were able to analyze 17 patients and in 6 of them, we found these antibodies in their [cerebrospinal fluid]," said Dr. Schneeberger.

Although the study was not powered to detect clinical outcomes, changes in Movement Disorder Society–Unified Parkinson's Disease Rating Scale III scores (motor function) and nonmotor PD symptoms including cognition, quality of life, and investigator-rated global evaluation, all showed "statistically significant or sometimes highly statistically significant results in favor of the antibody responders in this population," said Dr. Schneeberger.

"The most convincing" piece of evidence from the study is that "immune responders show a clinically better response than immunological non-responders" he said, and he emphasized the "consistency over all clinical endpoints"

"These results are quite exciting," added Walter Schmidt, PhD, chief executive officer of AFFiRiS, in a later interview with Medscape Medical News. "There seems to be some functional correlation between the presence of antibodies and beneficial clinical impact for patients."

However, he stressed that this is a phase 1 study and the numbers are small.

The company is planning a follow-up study to assess the safety and immunological consequences of a booster shot of the low- and high-dose vaccine.

Dr. Schneeberger predicted "optimistically" that it will take 6 years before the vaccine completes subsequent trial phases.

The study was funded by the Michael J. Fox Foundation. Dr. Schneeberger and Dr. Schmidt are employees of AFFiRiS.

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Cite this: Parkinson's Vaccine Looks Promising - Medscape - Aug 01, 2014.