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Checkpoint for genetic Disorders

Dr Talat Nasim is leading a group of British scientists on a new innovation in the treatment of genetic disorders.

portrait photo of Talat Nasim

Dr Talat Nasim, a Lecturer in the School of Pharmacy and Medical Sciences, has worked collaboratively to propose a new ‘Checkpoint Model’ that can be used to develop therapies for a wide range of genetic disorders.

The research, led by Talat, aims to reduce the symptoms of disorders caused by ‘nonsense mutation’: a mutation which stops DNA being translated into proteins that are crucial to normally functioning molecules in the body’s cells.  Nonsense mutation is connected to around 2500 genetic disorders, such as pulmonary hypertension, cystic fibrosis, and Duchenne muscular dystrophy, and results in conditions which can be devastating for patients and their families.

The research ‘Aminoglycoside-mediated promotion of translation readthrough occurs through a non-stochastic mechanism that competes with translation termination’ published in the Journal of Human Molecular Genetics has received substantial media coverage:

Talat explained “Many of the new drugs under development to treat these genetic disorders aim to boost production of these proteins by making the cellular machinery less sensitive to the premature ‘stop’ instructions. Our model acts like a simple roadside checkpoint. Compounds which can fulfil certain criteria will enable some proteins to get past the pre-mature stop signal.  Even a small amount of the right proteins would be enough to give some therapeutic protection, and that would lessen the symptoms of the disorder.”

The Team carried other associated works.  They have developed a number of more accurate cell-based screening assays based on this model: screened hundreds of genes and already identified two that could be targeted for drug development; tested more than 1000 FDA approved drugs to see if they could be repurposed to treat genetic disorders caused by nonsense mutations; and tested the compound PTC124 (view related publication) shown to boost production of dystrophin protein in young patients with Duchenne muscular dystrophy caused by nonsense mutations. It is thought that PTC124 does this by making the cell by-pass the premature stop signal.  Using the new methods, however, the Bradford researchers found that the compound does not work in this way.

The model developed by the Team could help reduce the high costs of drug development work in this area by ruling out compounds that are unlikely to have any therapeutic benefit at an earlier stage in the process

Talat has been acting as an Executive Member of the Global Network of Bangladeshi Biotechnologists (GNOBB), Bangladesh and an Adviser for the Commonwealth Scholarship Commission, UK. He is the founder and Chief Adviser of the organization called Centre for Health Agriculture and Socio-economic Advancements (CHASA), Bangladesh. His research interests lie within the broader areas of Translational Medicine ranging from target identification to drug discovery. He is the co-discoverer of a few key genes that cause a genetic disorder Pulmonary Arterial Hypertension and a blood disorder myodysplastic syndrome. Additionally, Talat has developed key techniques for studying mammalian gene expression and gene regulation, which are being widely used throughout the world.