A potential treatment for Parkinson’s has promising results

A little new test published in the magazine Nature Medicine describes what would be two new developments for Parkinson’s disease if they pan out: a diagnostic test and a potential immunological treatment that works similarly to a vaccine. The research is still early, but researchers are excited about the prospect of advances for a disease that lacks good diagnoses 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 functions and some cognitive functions. Although researchers have long known that these proteins are involved in the disease, finding ways to measure and target them has not been easy.

The (potential) Parkinson’s vaccine

Florida-based biotechnology company Vaxxinity has 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 incorrectly folded – and not the regular forms. This would essentially help people’s bodies heal themselves.

“The idea is that patients recognize their own misfolded proteins, and this 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 portion of the study.

The Parkinson’s test

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

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

see more information: Michael J. Fox: Pursuing Parkinson’s Treatments

The test overcomes these obstacles by intelligently exploiting the normal forms of the protein. Parkinson’s experts believe that small amounts of abnormal alpha-synuclein circulate in patients’ spinal fluid, but are too small to be detected by imaging tests. To perform the study’s new test, researchers take normal forms of the protein in the laboratory and add them to patients’ spinal fluid samples; which causes any misfolded proteins that may 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 the amount of antibodies generated by patients to the misfolded protein, resulting in a biomarker or surrogate for the treatment effect.

This test would be a critical advance because it allows us to identify patients with abnormal alpha-synuclein in the early stages of the disease, when treatments may be most effective.

With more patient data, researchers hope to further refine the meaning of the different levels, so that the test will be able to tell not only whether a person has Parkinson’s, but also whether someone is at a higher 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 approval of the test for wider use.

What the study found

The trial — led 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 designed solely to test the safety of the approach, so the study only provided hints about the treatment’s effectiveness. All received three injections in almost a year; some contained the treatment in different doses and some contained a placebo.

Overall, people who received the vaccine generated more antibodies against the abnormal alpha-synuclein protein than those vaccinated with a placebo, as measured by the Parkinson’s test. Antibodies began to rise about four months after 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 so safely, which is reassuring,” says Jean-Cosme Dodart , senior vice president. chair of research at Vaxxinity and senior author of the paper.

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