Myotonic dystrophy type 1 (DM1), the most common in adults, is an inherited, progressive disease that mainly affects the muscular system, but also the respiratory and central nervous systems. It is characterized by a reduction in muscle mass and by the appearance of damage that may be neurological, cardiological, respiratory, endocrinological or digestive.
The genetic origin of this neuromuscular disorder lies in an abnormal expansion of the myotonic dystrophy protein kinase (DMPK) gene sequence, which upon transcription forms special RNA structures that sequester the MBNL (muscleblind-like) proteins involved in the pathway of this pathogenesis. Most of the symptoms of the disease are due to the lack of MBNL function, and increasing the levels of these proteins has been shown to be therapeutic.
“A key aspect of the success of this research has been that it proposes a therapeutic strategy that has been little explored until now,” explains Rubén Artero, head of the Human Translational Genomics research group at the University of Valencia, whose team validated years ago the overexpression of MBNL proteins as a new therapeutic concept for DM1 and developed molecules that demonstrated their ability to recover symptoms of the disease in preclinical models. The invention was patented and the proof of concept of these new experimental drugs, in animals, was published in Nature Communications.
ARTHEx Biotech, the spin-off of the University of Valencia to which the patent was licensed, has been working since then on the development of ATX-01, an anti-miR oligonucleotide designed to antagonize microRNA 23b (miR-23b) involved in the pathogenesis of DM1. Now, the company has just announced the administration of this compound to the first participant in the randomized, placebo-controlled, double-blind Phase I-IIa clinical trial.
“If the trial is successful, the molecule developed by Arthex could become the first disease-modifying drug for myotonic dystrophy type I, the most common form of muscular dystrophy in adults”
The clinical trial
The main objective of ArthemiR™ -as the trial is called- is to determine the safety and tolerability of ATX-01, as well as its activity on the pathophysiology of the disease, in a total of fifty-six participants with DM1.
“If the trial is successful, the molecule developed by Arthex could become the first disease-modifying drug for myotonic dystrophy type I, the most common form of muscular dystrophy in adults,” says Beatriz Llamusí, executive scientific director and co-founder, together with Rubén Artero, of ARTHEx. “It is an experimental RNA-targeted therapy that consists of increasing in patients the levels of the MBNL protein, whose dysfunction has been linked to the most severe symptoms of people affected by myotonic dystrophy. The treatment also allows us to indirectly reduce the expression of DMPK, the mutant gene that causes the disease, so that the sum of both factors is expected to have a powerful therapeutic effect on patients”, points out the scientist and entrepreneur.
ATX-01 is the only therapeutic agent that acts with a dual mechanism of action, increasing the production of MBNL proteins and reducing the amount of RNA structures that sequester them. “With the administration of ATX-01 to the first participant in the ArthemiR™ trial, we are taking a step forward in our goal to meet important medical needs that will enable us to modify the course of the disease,” explains Frédéric Legros, President and CEO of ARTHEx. ‘We expect ATX-01 to lead to functional benefits for patients, offer a well-tolerated safety profile and improve the quality of life of affected individuals,’ adds Judy Walker, Executive Medical Director of the UV biotech spin-off.
Myotonic dystrophy type 1 (DM1) is a disabling disorder that affects more than one million people worldwide. The disease damages muscles and other tissues, causing respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment. It usually manifests during adulthood and there is currently no approved treatment to slow the progression of the disease.
ARTHEx Biotech is a clinical-stage biotech company specialized in the development of innovative drugs through the modulation of gene expression. The ArthemiR trial has been co-funded by the Accelerator program of the European Innovation Council (EIC).