United Neuroscience is developing a novel class of vaccines that target aberrant proteins implicated in neurodegenerative diseases. Now it has strong preclinical evidence showing that one of its vaccines could hold promise in Parkinson’s disease.
The vaccine candidate, dubbed UB-312, targets alpha-synuclein proteins, which reside in healthy brains but can also clump together to form insoluble "fibrils" commonly seen in Parkinson’s.
Preclinical data showed that UB-312 selectively targeted and prevented accumulation of misfolded alpha-synuclein proteins in cell and animal models of Parkinson's disease, as well as in post-mortem brain tissue from patients with Parkinson’s. The company presented the results at the Parkinson’s U.K. Research Conference.
United Neuroscience calls its candidates “endobody” vaccines.
“The concept we try to create with the term is that your body makes antibodies to control diseases inside the body that are not infectious, that are not cancer,” United Chief Medical Officer Ajay Verma, M.D., Ph.D., told FierceBiotech in an interview earlier this year.
Some people in their late 90s “autovaccinate” themselves, developing antibodies against rogue proteins that cause brain disorders, explained Verma. United pulled out the memory B cells from some of those people and used them as reference points to design synthetic vaccines that can teach the immune system to attack only the abnormal proteins, he said.
Alpha-synuclein proteins are a popular target in Parkinson’s research. One recent population study led by scientists at the Van Andel Research Institute found that people who have their appendixes removed early face a lower risk of developing Parkinson’s. The researchers suggest the explanation might lie in alpha-synuclein, which can travel from the nerves in the gut to the brain. Biotech companies such as Axial Biotherapeutics and Enterin are also looking at ways to block the protein in the gastrointestinal tract.
Dublin-based United believes its approach offers advantages over monoclonal antibodies that are being developed to fight brain diseases. For one, its vaccines are designed to induce B-cell-specific responses, which may help avoid safety issues such as T-cell-mediated encephalitis, CEO Mei Mei Hu told FierceBiotech.
What’s more, producing monoclonal antibodies is a complex, expensive process, and the drugs may require frequent infusions to maintain a therapeutic effect. United’s vaccines, by contrast, teach the body to do most of the work, and thus may be accessible to more people, said Hu.
United Neuroscience is testing its “endobody” approach in other brain disorders, including Alzheimer's. The company’s lead candidate, an anti-amyloid-beta vaccine called UB-311, safely induced high anti-amyloid-beta antibodies in all patients in a phase 1 study, the company announced a year ago, and the full phase 2 results are expected later this year.
The company plans to initiate a phase 1 trial of UB-312 in Parkinson's disease in 2019, it said in a statement.