Arrowhead Begins Early-Stage Clinical Trial of ARO-DM1 for DM1 Treatment

Preclinical studies indicate that ARO-DM1 effectively reduces muscular DMPK expression and alleviates spliceopathies, potentially enhancing muscle strength and function.

Arrowhead Pharmaceuticals, based in Pasadena, California, has initiated dosing of participants in a Phase 1/2a clinical trial to assess single and multiple ascending doses of ARO-DM1, an RNAi therapeutic, in people with type 1 myotonic dystrophy (DM1). This condition is the most prevalent form of adult-onset muscular dystrophy.

DM1 patients suffer from muscle degeneration, persistent muscle contractions, cataracts, and may experience heart conduction issues. Physical disability and shortened lifespan are common outcomes. Currently, no disease-modifying therapies exist for DM1, with treatments limited to managing symptoms through methods such as physical therapy and the use of assistive devices.

ARO-DM1 targets the dystrophia myotonica protein kinase (DMPK) gene in muscles. The root of DM1 lies in an expanded CUG trinucleotide repeat in the DMPK transcripts' 3’-untranslated region. These faulty transcripts disrupt normal messenger RNA splicing, leading to the disease's symptoms.

Data presented recently at the 2024 Muscular Dystrophy Association Conference demonstrated that ARO-DM1 led to over 80% reduction in DMPK levels in skeletal muscles of nonhuman primates, effects that lasted beyond 85 days. In DM1 model mice carrying the harmful DMPK transgene, a species-specific variant of ARO-DM1 (S-ARO-DM1) decreased DMPK-CUG expression and fixed the aberrant splicing.

Arrowhead Pharmaceuticals is dedicated to developing treatments for persistent diseases by silencing causative genes. Their RNAi-based therapies use an array of RNA chemistries and delivery methods to effectively suppress target genes, leveraging the body's natural gene silencing mechanisms.

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