Discovery of a rare muscle disorder

Dr. Andreas Unger (L) and Prof. Dr. Matthias Vorgerd (R)

Muscle weakness in the legs, an unsteady gait, permanent risk of stumbling – symptoms such as these are common in people suffering from muscle disorders. However, the patient who came to the university clinic Bergmannsheil with these health conditions didn’t match any known diagnosis. Following thorough examinations, the Bochum-based doctors realised that they were dealing with an entirely new disease.

“We carried out numerous additional diagnostic investigations,” explains Prof Dr Matthias Vorgerd from the Neurological Clinic Bergmannsheil. “But we were not able to isolate the responsible gene or protein at first.” As other members of the patient’s family were likewise affected, the doctors assumed the disease was a hereditary one; together with private lecturer Dr Sabine Hoffjan from the RUB Human Genetics Department, they initiated detailed genetic analysis – and made a discovery. The BICD2 gene was altered in all patients. The cause was subsequently verified after a second affected family had been examined.

BICD2 had been known to be a trigger of diseases – but nobody had yet described a BICD2 syndrome that manifested itself in altered skeletal muscles. The problem always originated from the nervous system. Now, doctors observed pathological changes in the lower leg and femoral muscles, whereas no changes were identified in the nervous system. Matthias Vorgerd decided to get to the bottom of this new muscle disorder. “It is important to describe the disease as thoroughly as possible, in order to arrive at statements regarding the heredity process, progression, and therapy options,” explains the neurologist. He additionally consulted the research group headed by Prof Dr Wolfgang Linke from the RUB Institute of Physiology.

The physiologists under the auspices of Dr Andreas Unger performed various lab tests to analyse cells from the biopsies of affected patients. Initially they recorded high-resolution images with the electron microscope. These images showed significant alterations in the normally very orderly arranged muscle structure. Myofibrils, basic components of muscle fibres, were observed with degenerations, other cell organelles were likewise affected. Mitochondria, the energy suppliers of cells, appeared with different shape and the Golgi apparatus, a post office for protein sorting, was larger and more dispersed than normally.

What is known is: when the pathologically changed BICD2 gene is translated into a protein, one single wrong amino acid is built in due to the defect in the genome. It doesn’t take more than that to strongly impair the function of the protein. The mutation is dominant; individuals whose chromosome in a chromosome pair carries a pathological mutation will develop the disease.

Source: Ruhr-Universität Bochum

Online gamers invited to tackle rare muscle disorder

Gamers who have helped scientists understand the structure of hundreds of complex proteins by playing an online protein folding game Foldit are being invited to help work out the structure of an abnormal protein that causes a disabling muscle disorder called limb girdle muscular dystrophy. The project hopes to enlist thousands of volunteers from around the world to help determine the shape of the protein that lies at the root of the disease.

Limb girdle muscular dystrophy, or LGMD, is a rare, inherited disorder that primarily affects the muscles of the upper arms and legs. As the disease progresses, it becomes increasingly difficult for people with LGMD to perform such common activities as lifting objects, standing up from a chair, or climbing stairs. As the disease progresses, it becomes increasingly disabling. Currently there is no effective treatment or cure.

Proteins are made of a string of molecules, called amino acids, which are linked together like beads on a string. The sequence of the amino acids determines the folded shape a protein takes, which in turn determines how the protein works. In order for proteins to function properly they must fold into the right shape. If they don’t, they won’t work well, if at all, which can result in disease.

In the new project, which will be launched on Limb Girdle Muscular Dystrophy Awareness Day, Friday, Sept. 30, the Foldit players will focus on a protein called dysferlin that is believed to help maintain muscle cells and allow them to recover from injury.

People who inherit genes responsible for one form of LGMD, called LGMD-2B, cannot make normal dysferlin. As a result, they become weaker and weaker as their muscles gradually deteriorate.

The goal of the project is to work out the structure of dysferlin to better understand how it functions and what other proteins it interacts with. This information could lead to better treatments and perhaps a cure. LGMD-2B is a special interest of the Jain Foundation, which was founded by Ajit Jain, whose son has the disease.

Full story can be found from University of Washington website.

Nestlé acquires Phagenesis aiming at dysphagia

Nestlé Health Science (NHSc) and Phagenesis announced that NHSc is entering into a staged, milestone-based acquisition of Phagenesis, a medical device company that has developed a new treatment for dysphagia.

Under the terms of the agreement, NHSc will make an upfront payment, followed by milestone-based funding, while Phagenesis completes the clinical evaluation of Phagenyx®. The staged acquisition will be based upon successful completion of European and US development programs anticipated by 2019. Financial terms have not been disclosed.

A press release can be found from Phagenesis website.