Neurogenetic disorder is a group of diseases or conditions that impair the functioning of the nervous system and muscles. Symptoms may include muscular weakness, rigidity, loss of muscular control, twitching and spasming (myoclonus), and muscle pain (myalgia). Neurogenetic disease can have many underlying causes including immunological and autoimmune disorders, viral infections, circulatory problems, stroke, tumors, the failure of the connections between the nerves and the muscle fibers, poisoning, chemicals, genetic/hereditary disorders and unknown causes.
Myopathies (muscle diseases) are diseases primarily resulting in primary muscle weakness. The Tajsharghi group has been investigating the genetic causes of muscle diseases for many years. We discovered a new entity of muscle disorders, 'Myosin myopathies', which are diseases due to genetic defects in myosin gene, one of the two most important proteins in muscle contraction. During our previous studies, we identified the causative gene in several new human muscle diseases, leading to accurate molecular diagnosis. These results have helped families and patients all round the world know the cause of their muscle problems.
We continuing to work on finding other genes for muscle diseases. We have collaboration with many centers and we receive samples for analysis from all round the world. In parallel, we are now researching possible treatments for diseases where we have identified the genes. We develop disease models for muscle diseases in Drosophila and use human skeletal muscle cultured cells to verify mutations as being pathogenic and to study functional and structural consequences of such mutations. Our research project also integrates molecular, and physiological technologies to investigate functional properties of the proteins and to clarify important questions on the molecular mechanisms leading to the phenotypes of the neuromuscular diseases. Emerging insights from models of diseases provide powerful leads for the identification of potential therapies to prevent disease progress. We generated the first Drosophila models of the recurrent Laing distal myopathy (K1729del), using CRISPR/Cas9 genome engineering, which was published in PNAS (PMID: 29946036). We showed that the animals recapitulated certain muscle morphological phenotypes manifest in Laing distal myopathy patients. Moreover, we identified a potential therapeutic approach involving an E3 ubiquitin ligases of the ubiquitin proteasome system that alleviates the muscle pathological phenotype associated with the mutation. This finding may be beneficial in patients with Laing distal myopathy.
We have close collaboration with the Laing Laboratory at the Harry Perkins Institute of Medical Research in Australia. Homa Tajsharghi was conducting research as a guest Professor at the Harry Perkins Institute of Medical Research during 2016-2017.
Professor Homa Tajshargi together with Professor Nigel Laing, Harry Perkins Institute of Medical Research.