New research reveals potential treatment for congenital muscular dystrophy

Published Date
Eleanor Snow

Swiss pharmaceutical company Santhera has shown that Omigapil, a drug originally developed for treatment of neurological disorders such as Parkinson’s disease, can improve symptoms of a severe type of congenital muscular dystrophy called merosin-deficient congenital muscular dystrophy (MDC1A) in a mouse model. Mice receiving Omigapil once a day had less severe symptoms of the disease when compared to mice not receiving the drug. Mice on Omigapil also tended to survive for slightly longer.

The severity of MDC1A can vary, but in the most severe cases babies born with MDC1A have reduced muscle tone and muscle weakness (sometimes called “floppy baby syndrome”). Skeletal malformations such as deformation of the spine also occur along with an inability to stand or walk, breathing problems, and it can lead to death in early life.

MDC1A is caused by mutations in the LAMA2 gene which leads to faulty production of a protein called ‘laminin-α2’. This protein is found in skeletal muscle and helps to maintain the structure of the muscle cells during contraction. Disruption of laminin-α2 levels results in muscle and nerve deterioration through a type of cell death known as ‘apoptosis’.


What did the research show?

In this study, researchers first sought to explain how Omigapil might be able intervene in the  processes in the cells that lead to the symptoms of MDC1A. They used molecular techniques to show that an enzyme called ‘GAPDH’ is involved in the muscle cell death process (apoptosis) in mice with MDC1A. Omigapil is thought to work by directly binding to GAPDH and blocking the enzyme’s actions, and the researchers suggest this is how Omigapil could reduce muscle cell death and improve symptoms of MDC1A.

The researchers then treated a mouse model of MDC1A with Omigapil. The drug was given by mouth once a day from soon after birth. As the researchers expected, Omigapil reduced muscle cell death and protected muscle tissue. Muscle fibres in these mice were healthier and showed less damage. As a result, mice receiving Omigapil had a higher body weight, less skeletal problems, and increased movement ability. Mice on Omigapil still died very young, but on average they had a slightly longer life expectancy than those not on the drug.

What does this mean for patients?

These results suggest that it may be worth testing Omigapil as a potential therapy for MDC1A. Omigapil does not target the primary genetic cause of the disease and so it cannot completely ‘cure’ MDC1A. However, the drug does seem to effectively target processes in the cell that lead to some of the symptoms of MDC1A, meaning it may be able to slow disease progression.

Previous therapies for MDC1A have focused on ‘replacing’ the faulty laminin α2 protein with similar proteins. However there are still many technical difficulties to overcome in protein replacement therapy, especially getting the protein into all of the muscles in the body. As Omigapil is an oral drug, many of these difficulties are bypassed. An added bonus is that the development of Omigapil is already well advanced; the drug has already been tested and proven to be safe for humans in large clinical trials for Parkinson’s disease and amyotrophic lateral sclerosis patients.

Santhera has already secured orphan drug status for Omigapil and is currently defining the details of their planned clinical trial and performing additional preclinical development work which is required because the drug will be tested in children for the first time. They intend to test the drug on three different types of congenital muscular dystrophy- Ullrich congenital muscular dystrophy, Bethlem myopathy and MDC1A.  

It cannot be certain that Omigapil will have the same beneficial effects in humans as it has in mice. Nevertheless symptoms of the disease which improved in mice after taking Omigapil are also present in the human disease, and Omigapil is therefore a promising therapeutic contender for treatment of MDC1A.

Further information and links

Download the MDC1A factsheet

Visit Santhera Pharmaceuticals’ website.

Read about the congenital muscular dystrophy research we fund:

The full original paper published in the Journal of Pharmacology and Experimental Therapeutics is available by subscription only. The article is written in technical language with no summary in layman’s terms. The reference for the paper is:

Erb M, Meinen S, Barzaghi P, Sumanovski LT, Courdier-Fruh I, Ruegg MA, Meier T. Omigapil ameliorates the pathology of muscle dystrophy caused by laminin-alpha 2 deficiency. J Pharmacol Exp Ther. 2009 Sep 16.

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