Pekka Kallunki, Principal Scientist at Lundbeck, is investigating antibodies that target Alpha synuclein, a protein commonly manifested in Parkinson’s disease. In Alzheimer’s disease, there have been some recent breakthroughs with lecanemab and donanemab showing significant effects on clinical endpoints.
Despite some shared similarities between Alzheimer’s and Parkinson’s, Parkinson’s therapeutic success is trailing behind. Antibody therapies such as cinpanemab and prasinezumab have fallen short when it comes to demonstrating clinical efficacy and safety.
In Parkinson’s disease, there are two mechanisms of action. The alpha synuclein antibodies can either function by preventing extracellular aggregates from entering neurons or reducing inflammation triggered by these aggregates.
Lundbeck is not the only company focused on developing an antibody for Parkinson’s disease. Lundbeck’s antibody was tested in a cellular model showing dose-dependent inhibition of synuclein seeding, similar to Roche’s antibody, while Biogen’s antibody showed no activity. This implies differences in binding strength and epitope targeting.
Target engagement was assessed via reduction in free monomeric alpha-synuclein in cerebrospinal fluid (CSF). In a Phase 1 study, Lundbeck’s antibody showed a 30–40% reduction in free monomer levels at high doses, implying strong binding to the more toxic oligomeric and fibrillar forms.
There is a pressing need for better biomarkers to track disease progression and treatment response. Promising tools include Imaging agents (e.g., AC Immune tracer), seeding assays for diagnostics, NFL, and tau for inflammation and neurodegeneration. However, these are still in development and not yet validated for clinical use in Parkinson’s.
The field is moving towards earlier intervention, with studies targeting prodromal or early-stage Parkinson’s patients. Success may depend on identifying subpopulations with faster progression and specific symptoms (e.g., REM sleep disorder, olfactory deficits). Lundbeck’s antibody, developed with Genmab and supported by the Michael J. Fox Foundation, is part of this next wave of therapeutic exploration.
