Parkinson’s vaccine targets toxic alpha-synuclein in Phase 1 trial
UB-312 antibodies reported to engage protein clumps, slow their buildup
The immune response triggered by UB-312, an experimental vaccine by Vaxxinity, effectively targeted alpha-synuclein protein aggregates and slowed their toxic buildup in the cerebrospinal fluid (CSF) of Parkinson’s disease patients in a Phase 1 trial, compared with those given a placebo, data show.
The full target engagement triggered by UB-312 in patients’ CSF — the fluid surrounding the brain and spinal cord — was confirmed by two techniques, called seed amplification assay (SAA) and a protein misfolding cyclic amplification assay (PMCA).
These results, Vaxxinity stated, validate its platform technology to target toxic proteins involved in neurodegenerative diseases.
“Showing target engagement has always been a key challenge to overcome in neurodegeneration, and is of critical importance when demonstrated — a milestone worth celebrating. It is beyond our expectation to see this in our Phase 1 trial,” Mei Mei Hu, CEO of Vaxxinity, said in a company press release.
‘Major milestone’ seen in immune response with Parkinson’s vaccine
According to Vaxxinity, these findings also support the potential of SAA and PMCA to assess patients’ response to UB-312 in clinical trials and the vaccine’s pharmacodynamic properties, its effects on the body.
Early trial results, released in June, showed UB-312 was safe and well tolerated, and the vaccine could produce an immune response against toxic alpha-synuclein protein aggregates.
“This is a major milestone for Vaxxinity in our quest to help Parkinson’s patients. Our candidate has shown target engagement of the toxic species of alpha-synuclein in patients, demonstrating … proof of the mechanism of our vaccine-derived antibodies specifically engaging with the toxic target in vivo,” Hu said.
Alpha-synuclein is the major component of Lewy bodies, protein clumps that develop inside nerve cells and contribute to neurodegeneration in Parkinson’s disease.
Vaxxinity’s experimental vaccine incorporates a synthetic fragment of the alpha-synuclein protein along with immune-stimulating molecules. Its specific purpose is to trigger the production of antibodies that target disease-associated forms of alpha-synuclein in the body. This way UB-312 is expected to initiate a robust immune response capable of mitigating the impact of protein aggregates and halting Parkinson’s progression.
The Phase 1 clinical trial (NCT04075318) consisted of two parts. The first tested the safety and immunogenicity of multiple doses of UB-312 in healthy adults.
Its second part tested two doses of UB-312 — 100 and 300 micrograms — against a placebo in 20 age-matched people with early stage Parkinson’s.
Results from the 13 patients who completed dosing with UB-312 showed that 12 of them (92%) developed antibodies against alpha-synuclein and these antibodies were detected in the CSF.
“Importantly, [alpha-synuclein] aggregation was slowed down in CSF samples” from treated patients, the company also stated in its release.
Supported by these results, the Michael J. Fox Foundation for Parkinson’s Research is funding a two-year project that uses the PMCA assay to analyze patients’ CSF to better characterize the UB-312 antibodies and assess target engagement. The project is a collaboration between Vaxxinity, the Mayo Clinic, and UTHealth Houston.
“Integration of critical biomarker insight into therapeutic development programs is essential for building confidence in the treatment approach, and for designing informative trials. We’re pleased to support efforts of this kind that can have major impact for people with Parkinson’s disease,” said Mark Frasier, PhD, chief scientific officer of the MJFF.
“We are endlessly grateful to the patients who participated, and to The Michael J. Fox Foundation and our collaborators for their work on these cutting-edge assays that supported this breakthrough,” Hu added.
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