ProMIS to Present Data on Potential of Antibodies to Target Toxic Alpha-Synuclein in Parkinson’s

ProMIS Neurosciences will present evidence of the selectivity of several of its antibody candidates to target the toxic forms of alpha-synuclein, a key component of Lewy bodies that underlie the development of Parkinson’s disease.

Neil Cashman, PhD, chief scientific officer of ProMIS, will present the study, “Targeting of Pathogenic Aggregated Alpha-Synuclein: Refining Antibody Epitopes by Design,” at the 14th​ International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders, taking place March 26–31 in Lisbon, Portugal.

In Parkinson’s disease, alpha-synuclein’s 3D structure is abnormal, or misfolded, promoting its aggregation into clumps and causing the death of dopamine-producing nerve cells — those responsible for releasing the neurotransmitter dopamine, which is critical for regulating brain cell activity and function.

ProMIS Neurosciences developed a technology to design antibody candidates that bind only to the toxic forms of misfolded proteins like alpha-synuclein.

This means that healthy alpha-synuclein proteins are left alone, allowing the protein to function normally inside the cells — alpha-synuclein plays a key role in the healthy brain, regulating the release of synaptic vesicles, “bubbles,” filled with chemical neurotransmitters (chemical messengers). The synapse is the junction between two nerve cells that allows them to communicate.

This regulation occurs when alpha-synuclein is in its healthy state, i.e., arranged in a tetramer — four units of the protein wrapped around each other.

In lab studies, the antibody candidates were able to protect rodent neurons against the toxicity of alpha-synuclein and inhibited the mechanisms involved in the protein’s propagation.

ProMIS Neurosciences’ lead antibody candidate, PMN310, is a potential treatment for Alzheimer’s disease, and was shown to attack only toxic forms of a protein linked to the disease — amyloid-beta — and not normal forms. This investigational therapy is expected to enter Phase 1 clinical trials in 2019.

“The ability to bind toxic forms and only the toxic forms of misfolded proteins in the brain has been a frustratingly elusive challenge in both Parkinson’s and Alzheimer’s drug development,” Cashman said in a press release. “This is largely because the toxic species of the affected proteins still share many similarities with the healthy forms of the protein, making them impossible to target with precision using traditional tools for developing antibodies.”

“Using our unique discovery platform, we have been able to successfully address this problem. Our data show we can raise antibodies that bind the toxic species and only the toxic species of alpha-synuclein with exquisite precision while preserving the healthy forms of the protein,” he added.