Q1 2026 Research Spotlights
March 31, 2026 Amy Easton
QurAlis reports positive interim data from ANQUR Trial
February marked a milestone for QurAlis’ team in the development of their Stathmin-2 antisense oligonucleotide (ASO). QRL-201 is a first-in-class, potent ASO precision therapeutic in development to restore STATHMIN-2 (STMN2) expression in ALS patients with the aim of modifying disease progression and improving outcomes. STMN2 is a protein important for muscle innervation that is regulated by TDP-43 and, due to improper inclusion of a cryptic exon, is downregulated in the majority of ALS patients. ANQUR, a proof-of-concept Phase I/II study, is the first-ever clinical trial to evaluate a potential therapy to rescue STMN2 expression in sporadic and genetic forms of ALS. T
he analysis of the interim data revealed that QRL-201 elevated wild-type STATHMIN-2 levels, had good exposure and biodistribution, and was well-tolerated in patients. In addition, pNFH levels were lowered in QRL-201-treated patients compared to placebo. We look forward to hearing more about this exciting milestone from QurAlis at our upcoming Annual Meeting on May 5th in Boston. Target ALS is proud to have supported the early preclinical validation of the Stathmin-2 ASO therapeutic approach in the Industry-led consortium led by Daniel Elbaum, CSO for QurAlis.
New in Science: Preventing RAN Translation as a Strategy to Mitigate C9ORF72–ALS/FTD Pathobiology
In this February’s issue of Science, a study led by Xin Jiang and several Target ALS-funded investigators aimed to elucidate the pathobiological mechanisms associated with the C9orf72 (G4C2)n hexanucleotide repeat expansion (HRE) mutation. Jiang et al. investigated whether dipeptide-repeated peptides (DPRs), produced through non-AUG (RAN) translation of (G4C2)n RNA, are the primary driver of C9orf72 mutation disease biology. Jiang et al. leveraged base-editing of the CUG start-codon upstream of the (G4C2)n repeat RNA sequence to inhibit RAN translation in mice and iPSC-neurons. Disease phenotypes were ameliorated in both models.
Altogether, the findings described by Jiang et al. suggest that DPRs, and not (G4C2)n RNA, are the primary drivers of C9orf72-ALS/FTD disease pathogenesis. Moreover, this study represents the proof-of-concept findings to capitalize on inhibiting RAN translation as a therapeutic strategy towards the treatment of C9orf72-ALS/FTD. However, two key questions remain towards elucidating C9orf72 mutation disease biology and inhibiting RAN translation: (1) is (G4C2)n RNA interacting with RNA binding proteins, directly or not, leading to significant differential gene expression and imparting cellular stress and toxicity, and (2) can inhibiting RAN translation be utilized as a long-term therapy?
Target ALS funds new precompetitive consortium tackling C9orf72 ALS and FTD
An abnormal hexanucleotide repeat expansion (HRE) within the non-coding region of the C9orf72 gene was first identified as a major genetic cause of ALS and FTD by Rosa Rademakers and team in 2011. Since that time, the complexity of C9orf72 RE biology has been underscored by failed clinical trials and the clinical heterogeneity in disease presentation and penetrance. The field has learned that repeat expansion length varies between individuals, across generations of families, and even between blood and brain samples from the same individual. To accelerate ongoing and future therapeutic development, Target ALS is pleased to announce a newly awarded 3-year project entitled“C9orf72 disease drivers: From genetic modifiers to toxic mechanisms.” This multi-disciplinary consortium is led by Rosa Rademakers of Vlaams Instituut voor Biotechnologie (VIB) who has partnered with her VIB colleague Renzo Mancuso, Marka VanBlitterswijk of the Mayo Clinic, Florida, and Adrian Isaacs of University College London.
This powerhouse collaboration brings together researchers from across the ALS and FTD research communities, combining their deep expertise in the genetics and molecular biology of the C9orf72 repeat expansion with deep technical expertise. Approaches include the use of human neurons and xenograft mouse models of transplanted human microglia to allow the team to dissect the toxic drivers that lead to motor neuron degeneration in the brain and spinal cord. Data from the study will be shared with researchers in industry and academia through the Target ALS Data Engine, further contributing to our already growing database from C9 carriers.
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