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Welcome to Molecular Medicine

- Beth Amato - Faculty Communications

The Division of Molecular Medicine and Haematology in the School of Pathology

The Division of Molecular Medicine and Haematology in the School of Pathology spearheads vital clinical and diagnostic work in both the private and public sectors. A joint initiative of Wits University and the National Health Laboratory Service, the division comprises specialised units focusing on science and research, teaching and learning and clinical work. It is represented in the main teaching hospitals, Charlotte Maxeke, Chris Hani Baragwanath, Helen Joseph, Rahima Moosa Children’s Hospital, and the Wits Donald Gordon Medical Centre.

The division plays a critical role in providing undergraduate teaching, as well as facilitating rigorous training for a large number of postgraduate students. The division provides specialist training to registrars preparing for College of Medicine examinations.

Division head, Professor Johnny Mahlangu

Figure 1: Professor Johnny Mahlangu, the division head at the Department of Molecular Medicine and Haematology in the School of Pathology

Professor Johnny Mahlangu heads the Division of Molecular Medicine and Haematology in the Faculty of Health Sciences of the University of the Witwatersrand and the National Health Laboratory Service. He is also a consultant clinical haematologist at the Charlotte Maxeke Johannesburg Academic Hospital. Professor Mahlangu received his undergraduate and postgraduate training in science and medicine at the University of the Witwatersrand with haematology specialist and clinical haematology sub-specialist qualifications through the Colleges of Medicine of South Africa. His main area of research is novel therapies in bleeding disorders, in which he has served as Principal Investigator for many international multicentre studies. He has published peer-reviewed journal articles and presented over 500 oral talks and posters at national and international scientific meetings. His academic citizenship includes membership in a wealth of national and international scientific committees.

Once-off gene therapy could resolve the many challenges of living with a bleeding disorder

A once-off adeno-associated gene therapy (AAV) for haemophilia types A and B will revolutionise the treatment of inherited bleeding disorders. There are promising results from four clinical trials which show that 80% of patients can live without replacement therapy and that the side effects of gene therapy are minimal.

Patients born with mutant F8 or F9 genes have impaired thrombin generation (the final and crucial step in clotting), resulting in spontaneous or trauma-induced bleeding. The hallmark of haemophilia bleeding is bleeding into the joints (known as haemarthroses).

The global standard of care for these patients is replacement therapy with plasma-derived or recombinant FVIII or FIX proteins. “Replacement therapy often results in suboptimal treatment. Moreover, the cost of treating haemophilia is about R400 000 to R600 000 per patient yearly. The development of alternative therapies such as gene therapy may be able to mitigate this,”  explains Professor Johnny Mahlangu, head of the Department of Molecular Medicine and Haematology in the Wits School of Pathology.

Now in its fifth year post-gene therapy, Mahlangu's research reveals that giving a single infusion of AAV-mediated gene therapy carrying the FVIII or FIX transgene results in. The patient’s quality of life drastically improves.

“In AAV-mediated gene therapy, the liver cells assist the transgene in finding its way to what is known as the hepatocyte nuclear. It then uses the hepatocyte protein synthesis machinery to transcribe the AAV-delivered FVIII or FIX gene into an mRNA. The vector isn’t integrated, so we aren’t changing anyone’s genetic makeup. ”

Figure 2: AAV mediated gene therapy

Figure 3: The lab has carefully controlled refrigeration, with remote sensing abilities

“This is the ultimate treatment that haemophilia patients require to remain bleed-free while not taking replacement therapy. Significantly, both the FDA and EMA have approved two gene therapies for haemophilia A and B, which are ommercially available. The major challenge in South Africa is that it is R60 million per treatment. Obviously, this isn’t affordable, but we are looking at models to see how we can make it viable,” says Professor Mahlangu.

Figure 4: Professor Mahlangu's world-class haematology clinical set-up