The neuronal protein alpha-synuclein has long been a target for Parkinson’s disease research, but it has delivered mixed results across multiple different therapeutics. Now, a team of scientists says a DNA-based vaccine was able to induce high levels of antibodies specific to that popular target in a mouse model.
The Institute for Molecular Medicine and collaborators tested four DNA vaccines in mice with the goal of targeting and preventing the pathology of Parkinson’s, Michael Agadjanyan, PhD, head of immunology at the institute, said in an interview.
The vaccine platform at the heart of this research was out-licensed to Nuravax last autumn. Agadjanyan is president of the nascent biotech.
Three of the vaccines targeted different B-cell epitopes—which are parts of an antigen recognized by the immune system—of alpha-synuclein. The fourth vaccine, known as PV-1950D, targeted three pathological epitopes simultaneously, which allows for a “broader immune response,” Agadjanyan said.
That last vaccine was the most effective at improving motor deficits in the mouse model, Agadjanyan said. The institute and collaborators from the National Institute on Aging, the University of California (UC), Irvine and UC San Diego reported their findings in Nature’s NPJ Vaccine this month.
Female mice produced higher levels of antibody response to the DNA vaccines than their male counterparts did, the study found. The researchers said they didn’t know whether the differing responses among sexes would translate from mice to humans. The neurodegenerative disorder is about 1.5 times more common in men than in women.
It will likely be another two to three years before Nuravax gets PV-1950D into a human clinical trial, Agadjanyan said. The company will need about $7 million to $8 million for studies leading up to the human trial, including safety and toxicology, he added.
If PV-1950D makes it into human clinical trials, it wouldn’t be the first vaccine to get tested against Parkinson’s. Swiss biotech AC Immune will test a vaccine targeting alpha-synuclein in a phase 2 trial after purchasing the jab, dubbed ACI-7104, from Affiris for $58.7 million last July. Vaxxinity is also studying an alpha-synuclein-targeting vaccine for Parkinson’s. The candidate, UB-312, is in a phase 1 trial slated to end in December, according to ClinicalTrials.gov.
Aside from vaccines, Big Pharma and fledgling biotechs alike have boarded the alpha-synuclein R&D train. Biogen exited in February, however, when its midstage monoclonal antibody failed. More recently, Novartis and Sanofi have hopped aboard. Novartis doled out $150 million upfront for UCB’s midphase small-molecule inhibitor in December, and Sanofi dished out $75 million upfront for a preclinical bispecific from ABL Bio this month.
