A-Synuclein, or Alpha Synuclein, is a protein created by the SNCA gene that helps nerve cells release neurotransmitters, keeping communication flowing smoothly throughout the brain. It’s a flexible material with no defined shape, likened to a strand of spaghetti moving freely in water, allowing the protein to easily adjust its shape and interact with surrounding membranes and molecules. However, when under stress, the protein is subject to misfolding and clumping together, forming Lewy bodies. It’s the abnormal buildup of this protein inside nerve cells that is the defining hallmark of Parkinson’s disease.
A vaccine-style therapy developed by the biopharmaceutical company, AC Immune, released its interim Phase 2 results of a new developmental drug called ACI-7104 for patients with early stages of Parkinson’s Disease. This vaccine-like candidate targets the α-synuclein, the toxic, misfolded protein that drives Parkinson’s disease. AC Immune positions its work at the forefront of precision prevention, relying on active immunotherapies (medicines designed to guide and assist the immune system) to help the immune system mount antibody responses for diseases such as Alzheimer’s, Down syndrome, and Parkinson’s Disease. ACI-7104 is designed to teach the body’s immune system to target the diseased forms of a-synuclein and protect the brain from further decline.
The Phase 2 trial included 34 people between the ages of 40 and 75 with early stages of Parkinson’s disease (most within two years of their initial symptoms), each receiving six injections of the treatment. Every single person who received ACI-7104 produced antibodies against the harmful protein. These antibodies were detected both in the participants’ blood and cerebrospinal fluid, suggesting that the vaccine successfully reached the intended brain regions.
Results during the trial indicated an increased antibody response in patients who received the vaccine, with no detectable signs in those receiving a placebo. There were also no signs of any serious effects reported by any individuals who received the treatment, but reports of headaches, fatigue, and soreness where the shot was administered were common.
People who received the treatment showed stabilization in several important biomarkers: Alpha-synuclein levels in spinal fluid remained steady (they normally drop as the disease worsens), nerve cell damage did not rise, suggesting less ongoing injury, and inflammation and stress in the brain decreased in treated patients. Also, the nerve cells in which dopamine is produced in the brain showed a minimal decline.
Results of the trial also indicate symptoms related to Parkinson’s progressed more slowly over a 74-week time period, while the symptoms worsened among people who received a placebo, consistent with the expected gradual progression of Parkinson’s.
Currently, there is no cure for Parkinson’s Disease, and no available treatment has been proven to slow or halt the disease. ACI-7104 is one of the first therapies to show consistent early signs of actually changing the course of the disease, not just treating its effects.
Public Comments from AC Immune
Following the release of the interim Phase 2 data, AC Immune and outside experts issued statements highlighting the strength of the efficacy trends and the possibility that ACI-7104 could alter the course of Parkinson’s disease.
Dr. Andrea Pfeifer, CEO of AC Immune SA, commented: “The interim Phase 2 data show the potential of our ACI-7104.056 active immunotherapy to slow the progression of Parkinson’s disease and hold the promise of a tremendous step forward for millions of patients. The consistent signs of efficacy, combined with the continuing strong safety record, underline ACI-7104.056’s potential to transform PD treatment and are a strong basis for accelerating development. We will discuss ACI-7104.056 with the regulators to establish a clinical development plan towards registration.”
Werner Poewe, MD, emeritus Professor of Neurology at Innsbruck Medical University and a leading expert in Parkinson’s disease, also stated : “The remarkable consistency of the trends observed across multiple disease-related biomarkers and on clinical assessments in the treatment arm is very promising. Importantly, clinical and biomarker outcomes provide signals that the immunological response elicited by ACI-7104 may be associated with beneficial effects on PD progression. Overall, these findings are highly encouraging and fully support further development of the program. If further substantiated, the current data would have major implications for future PD therapy. For the first time, we are seeing signals that targeting the underlying pathology of Parkinson’s with active immunotherapy could slow disease progression.”
