A therapeutic strategy based on alternative splicing of the MECP2 gene could restore protein levels in Rett syndrome, a neurological disorder caused by mutations in that gene. Scientists at Baylor College of Medicine have successfully tested this approach both in vitro in neurons from Rett patients that produce some functional protein, correcting the altered gene expression and improving neuronal functions, and in vivo in mice.
Researchers from the University of Oxford and the Health Research Institute La Fe (Spain) investigated the potential of multigene RNA-based therapeutics in Alzheimer’s disease, aiming to overcome potential compensatory mechanisms and patient heterogeneity.
Metabolic dysfunction-associated steatotic liver disease (MASLD) covers a series of pathogenic conditions including steatosis, inflammation and fibrosis with limited therapeutic options to date. Recent findings have shown upregulation of hepatic murine double minute 2 (MDM2) in patients with MASLD. Additionally, genetic deletion of hepatic MDM2 and its pharmacological inhibition were seen to improve steatosis and fibrosis in MASLD murine models.
Dentatorubral-pallidoluysian atrophy (DRPLA) is a lethal neurodegenerative disorder caused by pathogenic expansion of CAG repeats within the atrophin-1 (ATN1) gene. As DRPLA belongs to the broader class of repeat expansion disorders (RED) that are driven by toxic gain-of-function effects, reduction or elimination of ATN1 expression is predicted to provide therapeutic benefit.
Stoke Therapeutics Inc.’s speeded-up timeline for zorevunersen, the antisense oligonucleotide in development with Biogen Inc. as a first-in-class potential disease-modifying treatment for Dravet syndrome, put the rare, severe form of lifelong epilepsy in the spotlight. The news involved completion of enrollment and a phase III data readout from the Emperor study, as officials said signups of 150 patients are expected in the second quarter of the year, which puts the study on track for data in mid-2027.
Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Researchers from Sorbonne University and Hôpital Trousseau developed a targeted approach based on antisense oligonucleotides as a way to improve CF management.
As widely expected, GSK plc and Ionis Pharmaceuticals Inc. reported positive findings from two pivotal trials testing bepirovirsen in chronic hepatitis B, showing the antisense oligonucleotide therapy achieved a statistically and clinically meaningful functional cure rate, indicating a potential transition in CHB treatment beyond the current viral suppression-focused standard of care.
Alagille syndrome (ALGS) is a rare, multisystem genetic disorder most commonly caused by haploinsufficiency of the JAG1 gene, leading to reduced JAG1 protein function and impaired development of intrahepatic bile ducts. Researchers from Arnatar Therapeutics Inc. described the development of antisense oligonucleotides (ASOs) engineered using their proprietary ACT‑UP1 platform to upregulate endogenous JAG1 expression and thereby address the underlying genetic deficiency.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive degeneration of upper and lower motor neurons, resulting in paralysis and death typically within 3-5 years of symptom onset. Historically, treatment options have been extremely limited. However, the identification of genetic contributors to ALS pathogenesis has enabled the application of antisense oligonucleotides (ASOs) to selectively modify or reduce the expression of disease-associated genes at the RNA level.
Scineuro Pharmaceuticals Holdings Ltd. has received a $5 million research grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) to accelerate the preclinical development of the company’s novel LRRK2-targeted antisense oligonucleotide (ASO) program, SNP-614, for Parkinson’s disease.
