Myotonic Dystrophy Type 1: RNA-Targeted CRISPR Shows Promise in Mouse Model

According to a story from PR Newswire, the RNA-targeted gene therapy company Locanabio, Inc. has recently released findings from a preclinical evaluation of an RNA-targeted CRISPR Cas9 (RCas9) system as an intervention in a mouse model of myotonic dystrophy type 1 (DM1). The results were initially published in the scientific journal Nature Biomedical EngineeringScientists affiliated with the company collaborated with the University of Florida and the UC San Diego School of Medicine.

About Myotonic Dystrophy

Myotonic dystrophy is a form of muscular dystrophy. Its onset is later than many other forms, often beginning in the 20s and 30s (though it can begin at any time). In this long term disorder, the muscle systems contract and are unable to relax. The disease comes in two main forms: type 1, which is usually more severe and linked to mutations affecting the DMPK gene; and type 2, which is caused by mutations of the CNBP gene. Symptoms include progressive muscle weakness, muscle atrophy, heart problems, intellectual disability, cataracts, sleep apnea, and insulin resistance. Men may experience infertility and early balding. Muscle problems often begin in the feet, hands, neck, or face. There are no disease altering therapies for myotonic dystrophy, and treatment focuses on managing symptoms and complications. Common measures include pacemakers, non-invasive ventilation, and mobility aids such as braces or a wheelchair. The disease is estimated to affect around 30,000 people in the US. To learn more about myotonic dystrophy, click here.

Signs of Hope

The system was delivered using an AAV viral vector. Both systemic and intramuscular delivery was evaluated in both neonatal and adult myotonic dystrophy type 1 model mice. Expression of RCas9 was prolonged, being present even three months after dosing. The treatment had the effect of reversing myotonia (uncontrolled muscle contraction) as well as molecular characteristics of the disease. The mice that were treated did not display signs of serious adverse reactions to the treatment.

The results backed up earlier in vitro tests involving muscle cells derived from patients with type 1 myotonic dystrophy. The findings suggest that an RNA-targeted gene therapy could be an effective, disease-modifying therapy for this rare disease. This research received support from the Muscular Dystrophy Association.

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