UMass Chan licenses RNA-based treatment for fragile X syndrome to QurAlis Corporation

UMass Chan Medical School has entered into an exclusive license agreement with QurAlis Corporation, a clinical-stage biotechnology company targeting neurodegenerative and neurological diseases, for a novel RNA-targeted mechanism to restore functional protein for patients with fragile X syndrome (FXS).  

The agreement reflects QurAlis’ significant investment in UMass Chan technology and research led by the laboratory of Joel D. Richter, PhD, the Arthur F. Koskinas Chair in Neuroscience and professor of molecular medicine, which included UMass Chan colleagues Sneha Shah, PhD, assistant professor of molecular medicine, and Jonathan Watts, PhD, professor of RNA therapeutics, and Elizabeth Berry-Kravis, MD, PhD, of Rush Medical Center. It is the result of a 2024 partnership between UMass Chan and QurAlis to explore the biology of FXS to determine and confirm relevant targets that could enable antisense oligonucleotide (ASO)-mediated correction for FXS.

“This is a meaningful step in the process of taking basic biological discoveries and turning them into practical therapies that can benefit patients in the clinic,” said Dr. Richter. “QurAlis’ platform and expertise in neurodegenerative disorders is industry leading and is well positioned to address the mis-splicing of FMR1 RNA and restoration of functional FMRP protein expression. This partnership has not only validated our years-long research but also has resulted in the confirmation of a novel target for FXS, which we hope will lead to much-needed treatment options for FXS patients and their families.” 

FXS is the leading inherited form of intellectual disability and the most common single genetic cause of autism. The genetic condition caused is by a mutation of the FMR1 gene on the X chromosome. This mutation of FMR1 causes a range of developmental issues, including learning disabilities, behavioral challenges and cognitive impairment.

An orphan disease, FXS affects approximately 87,000 individuals in the U.S. alone—one in 4,000 men and one in 6,000 women. Males are more frequently affected than females, and generally with greater severity. In addition to intellectual disability, FXS patients are afflicted with a wide range of disabling symptoms including severe anxiety, social aversion, hyperactivity, hypersensitivity, developmental seizures and others. There are no effective disease-modifying treatments, although interventions such as special education, speech therapy, physical therapy, behavioral therapy and drugs providing symptomatic relief can provide the opportunity for optimizing a full range of skills. 

ASOs have shown incredible potential in the treatment of genetic disorders by targeting disease at the RNA level. ASOs are short, engineered single-stranded DNA/RNA molecules that can selectively bind RNA to regulate its expression in the cell. ASO technology may potentially treat neurodegenerative and neurodevelopmental disorders by changing the expression of genes connected to the disease.   

Leveraging its deep expertise in developing ASOs, QurAlis confirmed the findings from the Richter lab’s original publication and is advancing a new therapeutic that can potentially target up to 80 percent of FXS patients. Preliminary data of blood and cerebrospinal fluid measuring the mis-spliced FMR1-217 widely expressed throughout cortical brain areas affected in FXS suggests biomarker feasibility for detecting mis-splicing of FMR1 in patients with FXS. 

“FXS is a devastating neurodevelopmental disease with no effective disease-modifying therapies available,” said Kasper Roet, PhD, chief executive officer and co-founder of QurAlis. “Our initial partnership with UMass Chan confirmed that FMR1-217 is a validated genetic target for FXS.”

Dr. Roet added, “This groundbreaking discovery of a novel RNA-targeted mechanism to restore functional protein for FXS and the feasibility of a biomarker to detect mis-splicing of FMR1 in FXS patients opens up a completely new type of therapeutic approach through splice correction. We look forward to applying QurAlis’ FlexASO® platform and deep knowledge and expertise of ASO splicing targets toward having a candidate nominated for IND-enabling studies in the near future, so that we can bring a potential new precision medicine option to patients.”