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AAN 2025 | Promising vaccine targets for alpha-synucleinopathies

Johanne Kaplan, PhD, ProMIS Neurosciences, Inc., Cambridge, MA, discusses the identification of potential targets for vaccines to treat alpha-synucleinopathies. She highlights a study that used computational modeling to identify four dominant conformational epitopes that can be targeted by antibodies for vaccination. The study found that the antibodies induced by the vaccination were selective for toxic oligomers, and a combination of two epitopes was the most effective candidate for clinical development. This interview took place at the 77th American Academy of Neurology (AAN) Annual Meeting in San Diego, CA.

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Transcript

So we used a similar approach for alpha-synuclein. So again, using our computational modeling platform to model the misfolding of alpha-synuclein that gives rise to toxic species and what becomes exposed on these toxic forms of alpha-synuclein that we could vaccinate against. And once again, we found four dominant conformational epitopes, these little misfolded regions that are unique to toxic alpha-synuclein that can be a target for antibodies...

So we used a similar approach for alpha-synuclein. So again, using our computational modeling platform to model the misfolding of alpha-synuclein that gives rise to toxic species and what becomes exposed on these toxic forms of alpha-synuclein that we could vaccinate against. And once again, we found four dominant conformational epitopes, these little misfolded regions that are unique to toxic alpha-synuclein that can be a target for antibodies. And did mouse vaccination studies. And the antibodies that we induced by the vaccination were selective for toxic oligomers, no binding to monomers, no binding to Lewy bodies in the brains of Lewy body dementia patients. And so that’s what we wanted. And again, there’s many different combinations. So what are you going to put in a vaccine of these four? 15 possible combinations. And in this case, it was a combination of two of the epitopes that gave the maximal binding of high affinity antibodies binding toxic alpha-synuclein and brain homogenates from patients with Lewy body dementia. So that is what we chose as our clinical candidate for development to move forward, hopefully, into the clinic.

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Disclosures

Employee at ProMIS™ Neurosciences, Inc.