Beta-thalassaemia is a common form of inherited anaemia caused by reduced production of the beta-globin chains that, along with alpha-globin chains, form haemoglobin, the major oxygen carrying molecule in the body. The disrupted balance between the two chains leads to damage to developing red blood cells and is the major pathophysiological driver of the anaemia. Whilst treatments for symptoms are available they are not without their side-effects; beta-thalassaemia still causes thousands of premature deaths each year and so a curative therapy is desperately needed. Gene therapy using the recently developed CRISPR/Cas9 genome-engineering system offers itself as an attractive tool to develop novel therapeutic strategies.
My project aims to develop a gene-editing cure for beta-thalassaemia, with two major goals: 1) to identify and edit key regulatory sequences in the alpha-globin locus to restore globin-chain balance and ameliorate the anaemia. 2) to identify which fraction of the haematopoetic stem cell compartment should be edited to generate an efficient and acceptable therapy. We hope that if successful our project can be taken as a model for developing cures for a wide range of genetic diseases.
I am a Haematology registrar taking time out from training to undertake basic scientific research. I graduated from the University of Cambridge and trained as a paediatrician in North-East London prior to my current role.
Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia.
Mettananda S. et al, (2017), Nat Commun, 8
CLL with intra-cytoplasmic lymphocytic inclusion bodies.
Badat M. et al, (2016), Int J Hematol, 104, 411 - 412
Treatment of diffuse large B-cell lymphoma with secondary central nervous system involvement: encouraging efficacy using CNS-penetrating R-IDARAM chemotherapy.
Maciocia P. et al, (2016), Br J Haematol, 172, 545 - 553
Combination-therapy with concurrent deferoxamine and deferiprone is effective in treating resistant cardiac iron-loading in aceruloplasminaemia.
Badat M. et al, (2015), Br J Haematol, 171, 430 - 432
Gene Therapy in a Patient with Sickle Cell Disease.
Badat M. and Davies J., N Engl J Med, 376, 2093 - 2094