Therapeutic gene modulation of MBNL1-2 in myotonic dystrophy

Beatriz Llamusi Troisi


    Beatriz Llamusi Troisi


    Universitat de Valéncia, Spain


    Myotonic Dystrophy (DM) is a degenerative disease that causes severe multisystemic issues, involving symptoms in the nervous system, the skeletal muscle and the heart. Although considered a rare disease, is the most common muscle dystrophy condition in adults, and the only way of preserving a DM patient’s quality of life is by managing the symptoms. The molecular origins underlying DM are altered RNA metabolisms produced because the availability of some splicing factors in the cell, like the family of muscleblind-like (MBNL) proteins, is blocked.

    To develop a treatment for DM based on stopping the repressing of MBNL expression to reverse the RNA alterations that lead to the disease.

    Problem to Solve
    DM1 is the most common form of DM, which has an early onset during adolescence. Affected individuals have a shortened lifespan and there is still no effective treatment for them on the market. Overall, DM symptomatology affects a patient’s ability to work, which can greatly lessen their possibilities to find a job. Given the severity of a patient’s symptoms, finding a cure for this rare disease is an urgent medical need.

    The lack of MBNL factors in the cell is caused by an abnormal expansion of the myotonic dystrophy protein kinase (DMPK) gene sequence that, when transcribed, forms special RNA structures to sequester MBNL splicing factors. MBNL expression can be controlled through microRNAs (miRNAs). This project focuses on inhibiting these miRNAs to compensate for MBNL reduction in DM patients, which is an innovative approach with the potential to fight the disease.

    Level of Innovation
    MBNL factors are involved in other diseases besides DM due to their affinity to diverse RNAs that also contain sequence expansions. Therefore, the proposed approach could also be of further value in diseases such as spinocerebellar ataxia and Huntington’s.