ProMIS Neurosciences Targets Misfolded Protein in ALS Research Effort

ProMIS Neurosciences announced the start of a research program to identify new therapeutic targets on neurotoxic strains of a protein, TDP43, implicated in the development of  amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

TDP43 (TAR DNA-binding protein-43) is present in every cell and plays a key role in the response to oxidative stress, an event that compromises the health of cells. The protein, which also has a role in the expression and processing of genetic material, has been shown to lose its normal function in the context of neurodegenerative diseases such as ALS and FTD. This leads to the formation of intracellular aggregates of misfolded TDP43, which interfere with the production of cellular energy and protein degradation.

ProMIS uses two its computational discovery platforms, ProMIS and Collective Coordinates, to predict novel targets on the surface of abnormal (misfolded) proteins. Additionally, the company has also developed two technologies for the detection of very low levels of misfolded proteins in a biological sample. At the moment, ProMIS Neurosciences has three preclinical monoclonal antibody therapeutics against a target in ALS (misfolded SOD1 protein).

“ProMIS will apply its proprietary computational algorithms, supplemented by other methods pioneered by ProMIS scientists, to identify specific therapeutic targets on misfolded TDP43,” said Dr. Neil Cashman, the company’s chief science officer,  in a press release. “Our goal is to specifically target misfolded TDP43 without disrupting the critical role that normally-folded TDP43 plays in cell biology. ProMIS plans to validate the monoclonal antibodies we develop against misfolded TDP43 in diseased human tissue, and then select the ideal candidates to progress to drug development.”

The program adds to the company’s precision medicine approach to developing antibody therapeutics and companion diagnostic tools, especially for ALS and Alzheimer’s disease.