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.
