QR43 Platform™: Proprietary & Investigative TDP-43 Platform
Our QR43 Platform™ enables the discovery and development of first-in-class therapies for different TDP-43 diseases. This leading platform allows us to investigate disease drivers and potential therapeutics in human model systems with a comprehensive set of functional readouts.
Our team together with others in the field cracked the code on sporadic ALS through the identification of major disease drivers linked to TDP-43 pathology. Using human neuronal stem cell models from ALS patients, QurAlis co-founder and Harvard professor Kevin Eggan, PhD, discovered in 2019 that the expression of STATHMIN-2 (STMN2) is regulated by TDP-43. The Eggan Lab showed that loss of normal TDP-43 function leads to a highly significant decrease in expression of STMN2 and an impairment in neuronal repair which could be rescued by restoring STMN2 levels. These results were published in Nature Neuroscience.
In addition to nearly all ALS patients, TDP-43 pathology is also associated with approximately 50 percent of patients with frontotemporal degeneration (FTD), the second most common form of dementia; about a third of Alzheimer’s Disease patients; and up to seven percent of Parkinson’s disease patients.
This has given us genetic targets for sporadic patients to treat:
- Hyperexcitability induced neurodegeneration (negative feedforward loop on Kv7 gene regulation)
- Axonal instability and neuromuscular junction disintegration through STMN2 loss
- Toxic TDP-43 protein aggregates
FlexASO™ Proprietary Anti-Sense Oligonucleotide Splice Modulator Platform
The QurAlis FlexASO™ Splice Modulator Platform was developed to generate splice switching antisense oligonucleotides (ASOs) with higher potency and an increased therapeutic index. We are currently exploring this technology for different disease targets.
Antisense oligonucleotides are short, engineered single-stranded DNA/RNA molecules that can selectively bind RNA to regulate its expression in the cell. Our scientists are using ASOs to develop treatments for ALS that change the expression of genes connected with the disease.
By delivering these ASOs to motor neurons in ALS patients, we intend to target the mRNA of specific disease-related proteins, regulating the protein’s amount and countering the diseased pathway.
Since ALS is not one disease but in fact a spectrum of diseases with numerous distinct subgroups, ASOs are highly suitable drug candidates as they can be tailored for each specific patient sub-population.