- Lead therapeutic candidate for Alzheimer’s disease, PMN310, demonstrated selective binding and protection against toxic amyloid-beta oligomers
- Preclinical data support misfolded RACK1 as a potential target for ALS and FTLD-TDP
“We are pleased to share progress highlighting our ongoing effort to develop next-generation therapies for debilitating neurodegenerative disorders,” said Gail Farfel, Ph.D., Chief Executive Officer of ProMIS Neurosciences. “We are excited to share the data differentiating our lead therapeutic candidate for Alzheimer’s disease, PMN310, which exhibited characteristics in preclinical studies that may provide greater therapeutic potential and support a favorable tolerability profile compared to other amyloid-beta antibodies. AAN is also a great opportunity to present our data supporting the potential of misfolded RACK1 as a novel target for ALS and also FTLD-TDP, and our ability to generate antibodies that selectively bind aggregated RACK1 while avoiding benign isoforms.”
AAN Poster Details
Title: Protection Against Toxic Amyloid-beta Oligomers by PMN310, a Monoclonal Antibody Rationally Designed for Greater Therapeutic Potency in Alzheimer’s Disease
Session: P1: Aging and Dementia: Basic Science (abstract #4597)
Presenter: Johanne Kaplan, Ph.D.
Date & Time: April 23, 2023 from 8:00 – 9:00 a.m. ET
Evidence suggests that soluble toxic amyloid-beta (Aβ) oligomers, rather than Aβ monomers or plaque, are a primary driver of synaptic dysfunction, neuronal loss and cognitive decline in AD patients. However, it is difficult to specifically target toxic oligomers since they are much less abundant than other forms of Aβ in the brain. In the poster presented, clinical activity of various Aβ antibodies was shown to correlate with the ability to avoid monomer competition and retain binding to AD brain toxic oligomers. ProMIS’ lead therapeutic candidate, PMN310, showed selective binding to oligomers and was the least impacted by monomer competition compared to other Aβ-directed antibodies. Additionally, PMN310’s lack of binding to Aβ plaque observed in preclinical studies may reduce the risk of brain edema and microhemorrhages (ARIA) associated with plaque-binding antibodies. PMN310 protected memory function in two rodent models of AD, supporting further evaluation of the candidate as a potential therapeutic option for the treatment or prevention of AD.
Title: RACK1 Knockdown Is a Potential Therapeutic Target in ALS and FTLD-TDP
Session: P1: Aging and Dementia: Basic Science (abstract #3494)
Presenter: Neil Cashman, M.D.
Date & Time: April 23, 2023 from 8:00 – 9:00 a.m. ET
ProMIS has evaluated RACK1 as a potential target for ALS and FTLD-TDP. These neurodegenerative disorders are characterized by the formation of pathogenic aggregates of misfolded TAR DNA binding protein 43 (TDP-43) inside neurons which have been observed to co-aggregate with misfolded RACK1, a ribosomal protein. In a cell system, the misfolded form of RACK1 was detected by ProMIS antibodies selective for this RACK1 isoform.
The poster presented describes how RACK1 knockdown was able to reduce TDP-43 aggregation as well as alleviate the TDP-43-induced global suppression of translation in vitro. Knocking down RACK1 also reduced retinal and motor neuron neurodegeneration in D. melanogaster in vivo. These preclinical findings support misfolded RACK1 as a potential therapeutic target for TDP-43 proteinopathy in non-SOD1 and non-FUS ALS as well as FTLD-TDP.
Both poster presentations are available on the Poster and Publications page of the Company’s website at http://www.promisneurosciences.com
ProMIS Neurosciences Inc. is a development 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 is based on the use of two complementary techniques. The Company applies its 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. ProMIS is listed on Nasdaq and the Toronto Stock Exchange under the symbol PMN.
