Nathwani, AC;
Tuddenham, EGD;
(2020)
Haemophilia, the journey in search of a cure. 1960–2020.
British Journal of Haematology
, 191
(4)
pp. 573-578.
10.1111/bjh.17155.
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Abstract
The single most important step on the path to our modern understanding of blood coagulation and haemophilia in the 20th century was taken by British pathologist Robert Gwyn Macfarlane with his 1964 publication ‘An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier’. In the same year, Ratnoff and Davie in the USA reached the same conclusion. Macfarlane and Rosemary Biggs had previously, in 1952, discovered factor IX as the factor deficient in haemophilia B. In 1973, Arthur Bloom defined the distinct role of Factor VIII and von Willebrand factor in haemophilia A and von Willebrand’s disease respectively. This inspired the efforts of Tuddenham and his group towards the purification of Factor VIII which reached homogeneity in 1982, leading to the cloning of the Factor VIII gene in 1984 in collaboration with US scientists at Genentech, which in turn enabled development of safe recombinant factor concentrates for patients with haemophilia. Brownlee cloned the factor IX gene in 1982 at the Sir William Dunn Institute of Pathology in Oxford. This led eventually to the first successful trial of gene therapy for haemophilia B in 2011 by the Nathwani group at UCL, which built on pioneering work of US groups and was partnered with St Jude in Memphis where Nathwani started the project. This trial has fuelled the current quest for a functional cure of haemophilia A and B. The UK has, therefore, made a rich contribution to advances in haemostasis over the last 60 years, often in partnership with other groups across the world.
| Type: | Article |
|---|---|
| Title: | Haemophilia, the journey in search of a cure. 1960–2020 |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/bjh.17155 |
| Publisher version: | https://doi.org/10.1111/bjh.17155 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Hematology, haemophilia, blood coagulation, enzyme cascade, ADENOASSOCIATED VIRUS VECTORS, COAGULATION-FACTOR-IX, HUMAN-FACTOR-VIII, HIGHLY EFFICIENT TRANSDUCTION, GENE-TRANSFER, VIRAL VECTOR, HUMAN FIX, EXPRESSION, LIVER, THERAPY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10160680 |
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