Parkinson’s disease is a progressive neurological disorder that affects the nervous system of an affected individual and can cause devastating effects in a person’s motor abilities. Parkinson’s is the second-most common brain disease behind Alzheimer’s, and 1 in 100 adults over the age of 60 develop the disorder. Symptoms include tremors, slowed movement, rigid muscles, loss of automatic movements and speech impairments. These symptoms can be mild for years and can be barely noticeable in early stages, but they worsen in time and can bring about a list of complications including sleep disorders, dysfunction of bodily systems and cognitive problems.
One issue with treating and preventing the disease is the fact that the underlying cause of the disease is largely unknown, although many factors involved with the disease have been identified by researchers. The presence of Lewy bodies, or clumps of microscopic biological material, within a patient’s brain cells is a major indicator of Parkinson’s disease.
Another unknown factor in the progression of Parkinson’s disease is the role of the protein alpha-synuclein. In the brains of healthy patients, this protein is fairly common and may even play a role in brain functioning. Although it’s still unclear exactly how alpha-synuclein affects those with Parkinson’s, this protein is a major component of Lewy bodies. A lot of research has gone into attempts to understand the role of alpha-synuclein and Lewy bodies in this disease, and into the development of therapies that target the aggregation of alpha-synuclein.
AFFiRiS AG’s Parkinson’s Vaccine
On Thursday, July 31, representatives from the Michael J. Fox Foundation, an organization which has devoted $450 million to research into Parkinson’s disease since 2000, and AFFiRiS AG, a biotechnology firm based in Vienna, came together in New York City to announce the successes of a clinical trial for PD01A, a Parkinson’s disease vaccine. The Phase 1 clinical trial of PD01A, performed by AFFiRiS and supported by a $1.5 million grant from the Fox Foundation, found that the vaccine can safely and effectively reduce the aggregation of alpha-synuclein in a significant portion of the test population receiving PD01A.
The study looked at groups of patients receiving various levels of the PD01A vaccine and evaluated them over a 12-month period. Patients receiving the vaccine were given PD01A subcutaneously in four vaccinations, either in doses of 15 micrograms or 75 micrograms. Their progress was also evaluated against a control group of patients receiving standard symptomatic medication.
The study found that fifty percent of the patients who had been administered the vaccine developed antibodies specifically responding to the presence of alpha-synuclein. Not only did these antibodies exist in the brain, they were also found in serum samples of the cerebrospinal fluid of vaccinated patients. Professor Achim Schneeberger, MD, from AFFiRiS reported at the conference that the study had no dropouts, meaning all patients received vaccinations as planned, and explained that the test population correlated with the basic demographics for those at risk of Parkinson’s disease.
Of those who were immunized, 15 patients out of every 24 saw an increase in alpha-synuclein-specific antibodies. Interestingly, the antibody response was greater in the group of patients receiving the lower 15 microgram dose as compared to the group receiving the 75 micrograms of PD01A per vaccination. Also important was the fact that the vaccination was tolerated at the dosage levels administered and that there were no signs of a negative autoimmune response, which can sometimes occur in therapies which target proteins and other substances produced by the human body. The antibodies also spared beta-synuclein, a protein similar to alpha-synuclein, and only targeted alpha-synuclein aggregates.
As the press conference participants noted, this vaccination represents a very important milestone in the fight against Parkinson’s disease. PD01A marks the first time that a vaccine for Parkinson’s disease has been developed which targets the possible genetic causes of the disorder. Genetic data which pointed to the probable involvement of alpha-synuclein as a factor in Parkinson’s was discovered in the late 1990s, but this vaccine is the first time that knowledge has been leveraged for developing a therapeutic response to the disease. In his comments during the press conference, Schneeberger remarked on the critical role of the Fox Foundation in not only funding the AFFiRiS research but also helping to direct research and provide helpful knowledge within the field of research.
More Questions for the Future of PD01A
The findings related to PD01A’s efficacy in reacting to alpha-synuclein and possibly preventing Lewy bodies from forming are promising, but Prof. Schneeberger was careful not to exaggerate the benefits of this therapy. Although signs pointed to the therapy being beneficial to those at risk of developing Parkinson’s, “it’s not time to definitely say that we have benefits in motor symptoms,” said Schneeberger. However, it was stated that removing the clumps of alpha-synuclein aggregates would lead to healthy brain cell functioning, which is associated with functional improvement in patients. It is also possible that patients who have been administered the PD01A vaccine do not develop the antibodies to break down Lewy bodies, as antibodies were only discovered in half of the test population.
Researchers also have no reason to believe that this vaccination can help those who have already developed advanced symptoms in later stages of Parkinson’s. Although there are no signs that PD01A would negatively interact with deep brain stimulation (DBS) or other therapies, it’s generally believed in brain disease research that it’s almost impossible for the body to reclaim damaged brain cells. “It’s a prediction,” said Schneeberger. “We would love to be wrong, but that’s the way we think.”
Researchers at AFFiRiS are planning a boost study of PD01A to begin in September which will assess the effects of further vaccinations on patients and whether levels of PD01A can be boosted safely in these individuals and determining patients’ immunological responses. That boost study could take a year, and along with other necessary Phase 2 and Phase 3 clinical trials, it could be 8 years or more before this vaccine can be commercially licensed.
During the question and answer session, the panel of AFFiRiS and Fox Foundation representatives were inundated with questions from those seeking more information about getting involved in future vaccine trials. Todd Scherer, PhD, CEO of the Fox Foundation, noted many ways that those interested in Parkinson’s research and clinical trials can stay aware of recent developments and even possible studies in which they can be involved. Scherer told all those interested in applying to visit FoxTrialFinder.org on the Internet, which has helped connect thousands of volunteers with clinical trials in Parkinson’s disease, both those who have the disorder and those who do not but want to contribute to research. As their website states, anywhere from 40 percent to 70 percent of clinical trials face delays because they do not have enough participants. Although American trials of PD01A weren’t planned at the moment, but AFFiRiS representatives indicated that the possibility existed, pursuant to FDA approval, mainly owing to the strong partnership with the New York-based Michael J. Fox Foundation. The AFFiRiS web page about the company’s Parkinson’s clinical trials states that it doesn’t maintain a waitlist, but Schneeberger’s comments during the Q&A indicate that patients could reach out to find out more about upcoming trials being run by AFFiRiS. The biotech firm is also involved in developing therapies and cures for Alzheimer’s, diabetes and atherosclerosis.