Neurodegenerative diseases such as ALS, Alzheimer’s, and Parkinson’s affect more than 50 million people worldwide, robbing individuals of independence and placing a profound emotional and financial strain on families and healthcare systems. Despite decades of research, there are still no effective treatments that stop or reverse disease progression.

In ALS specifically, patients typically survive only two to five years after diagnosis, and current approved drugs only offer minimal benefit with about 6 months life extension. As such, there is an urgent need for new therapies that target the root cause of these diseases rather than just their symptoms.

Neuropeutics is addressing this unmet need by developing JRMS, a first-in-class small molecule that directly targets TDP-43 protein clumping, which is a key disease driver common across the wide range of neurodegenerative diseases. In 97% of ALS cases, toxic clumping of TDP-43 disrupts normal cell function and leads to neuron death. JRMS acts through a unique mechanism to prevent and reverse TDP-43 clumping, and that restores its normal localization, effectively addressing the root pathology rather than downstream effects.

Early studies in human cells and animal models have shown that JRMS reduces toxic TDP-43 protein clumps buildup and reverses clumps already formed at the time of treatment, offering strong proof of concept for disease modification. The program is now advancing through medicinal chemistry optimization and preclinical validation to select a lead development candidate for future clinical testing. This work is being advanced through a collaborative partnership between the Robertson Lab at the University of Toronto, Neuropeutics Inc, Toronto Innovation Acceleration Partners (TIAP) and AbbVie.

LifeArc contributes world-class medicinal chemistry and drug development expertise through Neuropeutics. AbbVie provides strategic guidance on industry insights and CMC development. Together, they are developing JRMS as therapeutic to extend patients’ lives and improve their quality of life, while also reducing the significant socioeconomic burden of ALS in Canada and worldwide.

Globally, 446 million people are affected by a rare genetic disorder (RGD). Standard-of-care genetic tests cannot deliver a diagnosis for 70% of these patients, limiting their access to specialized care and burdening healthcare systems.

Over the past decade, the EpiSign™ Research Program at LHSCRI has led the clinical application of DNA methylation patterns, called episignatures, establishing EpiSign™ as the world’s first and only clinically validated whole-genome epigenetic diagnostic test. The technology is deployed globally to diagnose unresolved RGDs and add functional context to variants of unknown significance.

EpiSign™ is entering the next stage of innovation with the release of EpiSign™ v6 to expand scope and capability in rare diseases. V6 will cover over 200 RGDs and nearly 500 canonical/non-canonical episignatures, including improved detection of mosaic, hypomorphic, and inverse patterns. These capabilities will strengthen diagnostic sensitivity, specificity, and interpretive power across the rare disease spectrum.

Complementing this, development is happening on EpiSign™ METRIC, a cloud-enabled analysis environment for processing DNA methylation microarray data with high throughput and accuracy. However, as 5-base sequencing technologies become integrated into routine clinical practice, there is a critical need for EpiSign™ to evolve beyond array-based data and peripheral blood.

This project will develop a synthetic reference framework that generates and validates high-fidelity methylation reference datasets across sequencing platforms and tissue sources. By creating privacy-preserving synthetic references, robust AI classifiers can be trained that maintain clinical performance without requiring the transfer or exposure of patient data. Deploying these new algorithms within a secure, distributed cloud infrastructure will enable scalable, privacy-preserving EpiSign™ testing within laboratories worldwide.

The outcome will be a unified, platform-agnostic epigenomic analysis system capable of integrating both sequence and methylation information, broadening EpiSign™’s clinical utility to hereditary and environmentally influenced conditions. This will lay the foundation for future applications in exposure-related and prenatal diagnostics, and position EpiSign™ as the cornerstone of next-generation clinical epigenomics-offering secure, cross-platform, and scalable diagnostic solutions that address one of medicine’s most persistent unmet needs.