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A vaccine for Parkinson’s disease could be on the horizon, according to a new study published in Nature Medicine.
Vaxxinity’s immunotherapy targeting pathogenic α-synuclein aggregates has achieved its immunogenicity, safety, and tolerability goals in a phase I clinical trial in Parkinson’s patients. The vaccine, known as UB-312, was shown to safely cross the blood-brain barrier and overcome immune tolerance by inducing antibodies against pathological forms of α-synuclein. These results align with what was previously seen in healthy patients treated with UB-312 and in preclinical studies, supporting the advancement of UB-312 to phase II clinical trials.
Searching for Parkinson’s immunotherapies
Because no approved therapies exist that can change the course of Parkinson’s disease, researchers are developing immunotherapies, such as monoclonal antibodies and vaccinations, to target pathogenic α-synuclein and improve Parkinson’s symptoms. While monoclonal antibodies that target pathogenic α-synuclein aggregates have shown promise in phase 1 trials, this immunotherapeutic approach has failed in phase II.
Vaxxinity has developed a vaccine-based immunotherapy for Parkinson’s disease. They picked UB-312 as their candidate from more than 60 synthetic peptide immunogens. Unpublished data has shown high immunogenicity in preclinical studies across species. The drug UB-312 has been shown to bind to α-synuclein inclusions in the brains of people who have Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy.
Not only that, but UB-312 elicits the body’s immune system to generate anti-α-synuclein antibodies, which fight oligomeric and fibrillar forms of α-synuclein that are harmful. These antibodies from UB-312 stopped motor function problems in a transgenic synucleinopathy mouse model. They also lowered levels of α-synuclein in the brain and gut and kept neurons safe in the lab.
UB-312 shows target engagement in Parkinson’s patients
In a prior phase I trial, increasing dosages of UB-312 demonstrated safety and tolerability in healthy participants between the ages of 40 and 85. The majority of adverse events were mild and short-lived. UB-312 caused the production of anti-synuclein antibodies, which were time- and dose-dependent and found in serum and cerebrospinal fluid (CSF).
This Nature Medicine article reports the findings of the second part of a phase II study conducted by Vaxxinity in collaboration with researchers from the Center for Human Drug Research and Leiden University Medical Center. The study assessed two distinct UB-312 treatment regimens for Parkinson’s disease patients regarding their immunogenicity, safety, and tolerability.
The researchers also looked at the possible application of the α-synuclein seed amplification assay (α-synuclein-SAA), which is increasingly used to diagnose Parkinson’s disease because it can find very small amounts of abnormal α-synuclein. It was also used as an experimental biomarker endpoint in this study to see how well UB-312-induced antibodies targeted a certain site. Other exploratory outcome measures included clinical efficacy assessments and cognition particular to Parkinson’s disease.
This clinical trial met its primary prespecified outcomes, showing that UB-312 treatment was generally safe and well tolerated. It generated a time-dependent increase in anti-α-synuclein antibodies in serum and CSF in patients with Parkinson’s. No substantial differences in treatment-emergent adverse events (TEAEs) were observed between the UB-312 and the placebo groups, with most TEAEs being transient and self-resolving.
Together, these data support the continued development of UB-312 as a disease-modifying treatment for Parkinson’s disease. Future studies should aim to find the best dose and antibody exposure in CSF over longer treatment periods and learn more about UB-312’s safety and effectiveness in synucleinopathies.
News & FeaturesImmunotherapyMedicine, Diagnosis, and TherapeuticsNervous system diseasesParkinson's diseasePharmacologySystemic conditionsTherapeutics