A monoclonal antibody that binds to alpha-synuclein is advancing into a clinical trial after showing positive results in the preclinical phase. The compound, known as ABBV-0805, was developed in collaboration between AbbVie and BioArctic, a Swedish biopharma company that focuses on neurodegenerative diseases.
In mouse models of Parkinson’s disease, ABBV-0805 bound to several different formations and sizes of aggregated alpha-synuclein, which are variably responsible for spreading alpha-synuclein and causing cell damage. ABBV-0805 reduced levels of alpha-synuclein by 60% vs a control antibody and prevented its spread. Further, it demonstrated a 100,000-fold selectivity for the toxic aggregated alpha-synuclein vs the harmless monomeric form, which plays an essential role in nerve cell function.
In a blinded survival study, mice were treated with ABBV-0805 or placebo starting at 12 months of age (when pathology appears in a murine model of Parkinson’s) and were terminated when they developed severe motor symptoms. ABBV-0805-treated mice survived for a median 160 days vs 84 days for placebo-treated mice. In a prophylactic setting, ABBV-0805 delayed the onset of severe motor symptoms and prolonged survival by 2 weeks vs placebo.
ABBV-0805 was also tested in the brain tissues of deceased patients with Parkinson’s, where it significantly reduced the levels of aggregated alpha-synuclein.
Based on these findings, ABBV-0805 will be studied in the clinical setting as a potential disease-modifying treatment for Parkinson’s disease and may be tested in dementia with Lewy bodies and multiple system atrophy in the future.