QurAlisQurAlis, a privately-held company specializing in precision medicines for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, has debuted its latest program. This initiative targets UNC13A RNA mis-splicing, a critical gene alteration present in ALS and frontotemporal dementia (FTD). FTD has recently gained renewed attention following the disclosure of Bruce Willis’ diagnosis of the condition. UNC13A is a vital regulator of neurotransmitter release at synapses, and the genetic alteration resulting in mis-splicing is estimated to occur in 58% of ALS patients and up to half of FTD cases.

To tackle this gene alteration, QurAlis has developed its proprietary FlexASO splice modulator platform. This technology uses antisense oligonucleotides (ASOs) to correct mis-splicing, restore UNC13A protein production, and reduce cryptic exons that may contribute to disease progression. Kasper Roet, QurAlis CEO, explained that “FlexASOs operate on the same mechanism of action as other splice-switching ASOs. However, incorporation of FlexASO technology improves the potency, safety, and biodistribution of oligos.”

QurAlis identified the critical genetic alteration in UNC13A as a key target for developing precision medicines for sporadic ALS and FTD populations through careful analysis of the gene’s pre-mRNA. Roet noted that UNC13A was previously identified as an ALS and FTD disease gene, supporting its importance in the development of disease. The company’s research team has focused on restoring the UNC13A protein and cellular function in ALS and FTD disease models.

“The development of appropriate human disease models was very complex,” Roet said. “We have resolved this by a dedicated group of researchers within our leading stem cell modeling group under the leadership of Sandy Hinckley our head of discovery.” 

FlexASO’s future impact on patients’ lives

Roet expressed enthusiasm for the UNC13A program, which is the company’s third initiative focused on a genetic target for developing precision medicines for sporadic ALS and FTD populations. “We look forward to advancing our UNC13A program along with our two lead clinical programs in ALS and a robust pipeline so that we can make a real difference in patients’ lives,” he said. Roet anticipates that the UNC13A therapy could significantly improve the lives of ALS and FTD patients by potentially slowing or halting disease progression.

Dr. Angela Genge, chief medical officer of QurAlis, will introduce the company’s UNC13A program during an oral presentation at the 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Congress. Dr. Genge’s presentation, “Gene Directed Therapy for Sporadic ALS,” is scheduled for March 21, 2023.

QurAlis believes the FlexASO splice modulator platform offers the potential to significantly impact the treatment of ALS and FTD.

As QurAlis unveils its latest program to address ALS and FTD, the journey to better understand and develop treatments for these complex neurodegenerative diseases continues. While challenges remain, the scientific community’s collective efforts in unraveling the mysteries of these conditions offer hope for patients and their families as they navigate the road towards potential therapies. Having recently closed an oversubscribed $88 million Series B financing, the company should be well-funded for the endeavor.