Vaxxinity Demonstrates Target Engagement of Toxic Alpha-Synuclein in Parkinson’s Patients - Seite 2

Analyses from this and related research yielded insights about the pharmacodynamic effects of anti-aSyn antibodies generated by UB-312 in the Phase 1 trial.

• UB-312-derived antibodies show preferential binding to aggregated aSyn isolated from patients with PD and Multiple System Atrophy (MSA), as measured by dot blot. Preclinical data published in Alzheimer’s Research & Therapy in 2020 showed similar characteristics of UB-312-derived antibodies.
• UB-312-derived antibodies successfully demonstrate inhibition of aggregation of aSyn in both a seed amplification assay (SAA) and a protein misfolding cyclic amplification assay (PMCA). These techniques can potentially be used to identify people with PD, and also to measure the treatment response and pharmacodynamic properties of UB-312-derived antibodies from subjects in clinical trials.
• Importantly, aSyn aggregation was slowed down in CSF samples from PD patients who received UB-312, as compared to those who received placebo, in the Phase 1 trial.
  

Vaxxinity plans to continue analyses of the clinical data as part of the collaborative project with MJFF, in addition to completing other target engagement assays and additional antibody characterization studies for binding kinetics and specificity. Mark Frasier, Ph.D., Chief Scientific Officer of MJFF, commented, “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.”

More information about the Phase 1 trial is available at https://clinicaltrials.gov/ct2/show/NCT04075318.

About Parkinson’s Disease

Parkinson’s disease (PD) affects approximately one million people in the United States and more than 10 million people worldwide. PD is a chronic and progressive neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic”) neurons in the substantia nigra area of the brain. While today’s approved products are aimed at providing symptomatic relief, they often produce significant side effects and lose their beneficial effects over time. There are no currently approved disease-modifying therapeutics for PD. Alpha-synuclein (aSyn) is a protein highly expressed in neurons, mostly at presynaptic terminals, suggesting a role in synaptic vesicle trafficking, synaptic functions and in regulation of neurotransmitter release at the synapse. Mutations in the gene encoding aSyn are known to cause or increase the risk of developing PD or dementia with Lewy bodies (DLB) and have been shown to alter the secondary structure of aSyn, resulting in misfolded and aggregated forms of the protein (i.e., pathological forms). While mutations in the aSyn gene are rare, aggregates of aSyn in the form of Lewy bodies (LB) and Lewy neurites are common neuropathological hallmarks of both familial and sporadic PD, suggesting a key role of aSyn in PD neuropathogenesis. Immunotherapy approaches targeting aSyn have been shown to ameliorate aSyn pathology as well as functional deficits in mouse models of PD and are now being investigated in the clinic.