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Development of a Method for Assessing the Effectiveness of Alpha-synuclein Immunotherapy

Study Rationale: Parkinson’s disease (PD) is characterized by the buildup of misfolded forms of alpha-synuclein. A vaccine designed to target this abnormal protein has demonstrated safety, tolerability, and an ability to invoke an immune response in a Phase 1a clinical trial in healthy individuals. As this vaccine candidate, called UB-312, advances to testing in people with PD, methods are needed to assess whether the antibodies produced in vaccinated individuals effectively neutralize abnormal alpha-synuclein. In this study, we explore whether a method that detects very small amounts of misfolded proteins in biofluids can determine whether UB-312 reduces abnormal alpha-synuclein in individuals with PD.

Hypothesis: We hypothesize that Protein Misfolding Cyclic Amplification (PMCA) — a method for rapidly detecting small amounts of misfolded proteins — will be sufficiently sensitive to allow assessment of UB-312’s effectiveness in reducing abnormal forms of alpha-synuclein in the cerebrospinal fluid (CSF) of people with PD.

Study Design: The UB-312 vaccine is now advancing into a phase 1b trial to confirm the safety and immunogenicity of two doses in individuals with PD. Antibodies induced by UB-312 immunization in individuals participating in our clinical trial will be purified from serum and characterized for their binding and neutralizing properties, including their ability to block aggregation of abnormal alpha-synuclein as measured by PMCA. A direct assessment of abnormal alpha-synuclein by PMCA will also be performed on CSF samples collected from participants receiving either UB-312 treatment or placebo.

Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, this project will advance the use of PMCA as a method to assess the neutralization of alpha-synuclein in future clinical trials, facilitating a more rapid determination of whether investigational drugs are demonstrating the expected mechanism of action for the treatment of PD.

Next Steps for Development: Combined with clinical outcome measurements, this method of assessing abnormal alpha-synuclein will be implemented in Phase 2 clinical trials in people with PD to further assess its predictive value for monitoring clinical efficacy.


  • Jean-Cosme Dodart

    Boston, MA United States

  • Hui Jing Yu

    Dallas, TX United States

  • Wolfgang Singer

    Rochester, ME United States

  • Claudio Soto, PhD

    Houston, TX United States

  • Mohammad Shahnawaz

    Houston, TX United States

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