ProMIS Neurosciences Publishes in the Journal of Biological Chemistry on the Interaction Between Pathogenic Proteins as a Treatment Target for ALS
Study results support ProMIS’ TDP-43 misfolding-specific epitope as a potential therapeutic target for Amyotrophic Lateral Sclerosis (ALS)
CAMBRIDGE, Massachusetts and TORONTO, Ontario, April 09, 2024 (GLOBE NEWSWIRE) -- ProMIS Neurosciences Inc.(Nasdaq: PMN), a biotechnology company focused on the generation and development of antibody therapeutics targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), today announced the publication of supportive preclinical data in the Journal of Biological Chemistry in an article titled, “Tryptophan residues in TDP-43 and SOD1 modulate the cross-seeding and toxicity of SOD1." ProMIS is developing antibodies selectively targeting misfolded forms of TDP-43 and SOD1.
ALS is a fatal neurodegenerative disease of motor neurons. Toxic aggregates of superoxide dismutase-1 (SOD1) and TAR DNA-binding protein 43 (TDP-43) in motor neurons are characteristic of ALS.The study showed that these two proteins interact such that misfolding of TDP-43 leads to misfolding and aggregation of SOD1 in a cell system and promotes motor neuron damage in zebrafish.
“Publication of these data underscores the connection of misfolded proteins and ALS and supports targeting our TDP-43-specific epitope with PMN267 as a potential therapeutic approach,” stated Neil Warma, Chief Executive Officer of ProMIS Neurosciences. “PMN267 is advancing through preclinical development and is showing promise as a potential treatment for ALS. We are particularly pleased to have our data published in this well-regarded, peer-reviewed journal as it adds to the growing body of scientific knowledge on the pathogenic role of misfolded proteins in neurodegenerative diseases.”
The study demonstrated a pathologic synergy between SOD1 and TDP-43 in cell culture and in zebra fish.The interaction between these 2 proteins was characterized at the molecular level.The results indicated that the misfolded TDP-43 epitope previously identified by ProMIS and targeted by PMN267 contains a tryptophan amino acid critical to the pathogenic interaction with SOD1 thereby providing further biological support for the potential of therapeutic intervention with PMN267.
“These findings provide an important contribution to our understanding of ALS/FTLD molecular pathology and continue to validate our approach of targeting misfolded proteins as a therapeutic strategy that translates across multiple neurodegenerative diseases,” said Neil Cashman, M.D., Chief Scientific Officer and Co-founder of ProMIS.
The complete article can be accessed online here.
About ProMIS Neurosciences Inc.
ProMIS Neurosciences Inc. is a clinical stage biotechnology company focused on generating and developing antibody therapeutics selectively targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA). The Company’s proprietary target discovery engine applies a thermodynamic, computational discovery platform - ProMIS™ and Collective Coordinates - to predict novel targets known as Disease Specific Epitopes on the molecular surface of misfolded proteins. Using this unique approach, the Company is developing novel antibody therapeutics for AD, ALS and MSA. ProMIS has offices in Toronto, Ontario and Cambridge, Massachusetts.
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Source: ProMIS Neurosciences Inc.
Released April 9, 2024