A Potential Parkinson’s Treatment Has Promising Results

A Potential Parkinson’s Treatment Has Promising Results

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Publish Date:
21 June, 2024
Natural Cures
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A small new trial published in the journal NatureMedicine describes what would be two firsts for Parkinson’s disease, if they pan out: a diagnostic test and a potential immune-based treatment that works similarly to a vaccine. The research is still early, but researchers are excited by the prospect of advances for a disease that lacks good diagnostics and treatments.

The target of both innovations is alpha synuclein, a protein that takes an abnormal form in Parkinson’s patients—aggregating in their brains and destroying nerve cells involved in motor and some cognitive functions. While researchers have long known that these proteins are involved in the disease, finding ways to measure and target them has not been easy.

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The (potential) Parkinson’s vaccine

The Florida-based biotech company Vaxxinity developed a vaccine, or what it calls an active immune medicine, to train the immune system to attack only abnormal versions of the protein—which are improperly folded—and not the regular forms. This would essentially help people’s bodies 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,” says Dr. Mark Frasier, chief scientific officer at the Michael J. Fox Foundation for Parkinson’s Research, which funded the testing part of the study.

The Parkinson’s test

The new diagnostic test for Parkinson’s, which was developed by researchers at University of Texas and Vaxxinity, uses samples of cerebrospinal fluid to measure a person’s levels of abnormal alpha synuclein. If the U.S. Food and Drug Administration (FDA) grants it full approval, it will become the first test for diagnosing Parkinson’s. (The FDA classified it as a breakthrough device in 2019, a status that expedites access to innovative technologies where there is unmet need.) “Without [such a test], you’re kind of shooting in the dark,” says Mei Mei Hu, CEO and co-founder of Vaxxinity.

Alpha synuclein has been tricky to measure in the body for several reasons, says Frasier. While everyone has the protein, abnormal forms of it occur in relatively small amounts, so they’re harder to detect via imaging. This type of alpha synuclein also tends to clump inside cells rather than outside of them, making it even harder to see. If clumps are large enough to become detectable, they can look structurally similar to amyloid or tau—the proteins implicated in Alzheimer’s disease—so imaging tests might misdiagnose people with Alzheimer’s rather than Parkinson’s.

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The test overcomes those hurdles by cleverly exploiting normal forms of the protein. Parkinson’s experts believe that tiny amounts of abnormal alpha synuclein circulate in the spinal fluid of patients, but are too small to be detected through imaging. To run the new test in the study, researchers take normal forms of the protein in the lab and add them to samples of spinal fluid from patients; that prompts any misfolded protein that might be present in the samples to pull the normal proteins into misfolded aggregates, amplifying the signal for the abnormal form. Scientists then use a fluorescent probe to detect how much antibody to the misfolded protein patients generated, resulting in a biomarker, or stand-in for the treatment effect.

This test would be a critical advance because it makes it possible to identify patients with abnormal alpha synuclein at the earliest stages of the disease, when treatments might be more effective.

With more data from patients, researchers hope to further refine what different levels mean, so that the test will be able to tell not just if a person has Parkinson’s but whether someone might be at a greater risk of developing it. Currently the test is only used in research studies, but more results like these—as well as data on whether the same process can be applied to blood samples—could speed the test to getting approved for wider use.

What the study found

The trial—conducted by researchers at the University of Texas, the Mayo Clinic, the Michael J. Fox Foundation for Parkinson’s Research, and Vaxxinity—included 20 people with Parkinson’s. It was just designed to test the safety of the approach, so the study only provided hints about the treatment’s effectiveness. Everyone received three shots over nearly a year; some contained the treatment at different doses, and some contained a placebo.

Overall, people receiving the vaccine generated more antibodies against the abnormal alpha synuclein protein than those vaccinated with placebo, as measured by the Parkinson’s test. Antibodies started to ramp up about four months after the vaccinations began.

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“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,” says Jean-Cosme Dodart, senior vice president of research at Vaxxinity and senior author of the paper.

According to the test results, about half of the patients in the trial showed high levels of antibodies against the misfolded alpha synuclein, and most of these patients received the highest dose of the vaccine. They also scored the highest on motor and cognitive tests. There were too few patients to adequately assess any changes of Parkinson’s symptoms, but the researchers believe that longer follow-up with those tests, and potentially more frequent or higher doses of the vaccine, could lead to improvements in those scores. “The results are very, very encouraging,” says Dodart.

“This paper demonstrates that in a small number of people, the vaccine is having an impact on misfolded alpha synuclein, which is really exciting,” says Frasier. “We are now in the biological era for Parkinson’s disease.”