A groundbreaking small trial published in the journal Nature Medicine reports two potential firsts for Parkinson’s disease: a diagnostic test and an immune-based treatment akin to a vaccine. Although the research is in its early stages, the findings are generating excitement for advancements in a disease that currently lacks effective diagnostics and treatments.
The key focus of both innovations is alpha-synuclein, a protein that, in its abnormal form, aggregates in the brains of Parkinson’s patients and damages nerve cells crucial for motor and cognitive functions. Despite long-standing awareness of this protein’s role in Parkinson’s, finding ways to measure and target it has been challenging.
The Potential Parkinson’s Vaccine
Florida-based biotech company Vaxxinity has developed a vaccine, referred to as an active immune medicine, designed to train the immune system to specifically attack the misfolded, abnormal versions of alpha-synuclein while sparing the normal forms. This approach aims to enable patients’ bodies to treat themselves.
“The idea is that patients should recognize their own misfolded proteins, and it is personalized because their own immune systems are doing the work,” explained Dr. Mark Frasier, chief scientific officer at the Michael J. Fox Foundation for Parkinson’s Research, which funded the study.
The Parkinson’s Diagnostic Test
Researchers at the University of Texas and Vaxxinity have developed a new diagnostic test using cerebrospinal fluid samples to measure levels of abnormal alpha-synuclein. If the U.S. Food and Drug Administration (FDA) grants full approval, it would become the first test for diagnosing Parkinson’s disease. The FDA had previously classified it as a breakthrough device in 2019 to expedite access to this innovative technology.
“Without such a test, you’re kind of shooting in the dark,” said Mei Mei Hu, CEO and co-founder of Vaxxinity.
Alpha-synuclein has been difficult to measure due to its relatively small amounts and tendency to clump inside cells. The new test circumvents these issues by using normal forms of the protein to amplify the signal of misfolded proteins, which are then detected using a fluorescent probe. This creates a biomarker to stand in for the treatment effect.
This advancement could allow early identification of Parkinson’s patients, making it possible to start treatments when they might be most effective. Further research aims to refine the test to indicate not just the presence of Parkinson’s, but also the potential risk of developing the disease.
Study Findings
The trial, conducted by the University of Texas, the Mayo Clinic, the Michael J. Fox Foundation, and Vaxxinity, involved 20 Parkinson’s patients. It primarily assessed the safety of the vaccine approach, offering preliminary hints about its effectiveness. Participants received three shots over nearly a year, with some receiving different doses of the treatment and others a placebo.
Results showed that those receiving the vaccine generated more antibodies against abnormal alpha-synuclein than those given the placebo, with antibody levels increasing about four months after the vaccinations began.
“What is unique about our technology is that it can stimulate the immune system to produce very, very specific antibodies against toxic forms of alpha-synuclein, and do it in a safe way, which is reassuring,” said Jean-Cosme Dodart, senior vice president of research at Vaxxinity and lead author of the study.
Approximately half of the patients showed high antibody levels against misfolded alpha-synuclein, particularly those who received the highest vaccine doses. These patients also scored the highest on motor and cognitive tests. Although the small sample size limits the assessment of symptom changes, researchers believe that longer follow-up and potentially higher or more frequent doses could improve these scores.
“This paper demonstrates that in a small number of people, the vaccine is having an impact on misfolded alpha-synuclein, which is really exciting,” said Frasier. “We are now in the biological era for Parkinson’s disease.”
