DGEMBE: Developing GEnomic Medicine BEtween Africa and the UK

Novel genomic technologies are in the process of revolutionising care for patients with rare diseases in the Western world, enabling a greater scale of molecular diagnoses among affected people and pointing the way to new approaches to risk stratification and effective molecularly driven therapies. Nevertheless, there is a risk that the African continent may be left behind in this revolution. Indeed, existing health inequalities may be worsened through lack of availability of genomic technologies and, critically, the human capital to use them effectively in both the research and clinical settings in Africa. This project will utilise the strengths of its partners to counter that risk by developing an international cadre of trainees committed and appropriately trained to implement genomic medicine in the African context.

The partners are The University of Cape Town, one of the Southern hemisphere's leading medical research institutions; and The University of Manchester, a leading centre for rare disease research and genomic medicine. We will develop a cohesive programme of work involving basic science and clinical academic Principal Investigators; clinicians in cardiology, clinical genetics, audiology, ophthalmology and dermatology; health service clinical scientists, and genetic counsellors. This will as its central goal deliver ten reciprocal PhD student exchanges with the aims of making new genetic discoveries in both South African and UK patients, exploring the pathways to clinical benefit of the knowledge obtained, and laying the foundations for long-lasting South/North collaborations. Students in the programme will develop international links that will be of use in furthering their careers, and develop lasting commitments to promoting social and economic development in Africa through research interactions and knowledge transfer. In addition to the student exchanges, annual meetings between PI's, and longer PI-to-PI visits, will enable the development of major strategic partnerships in this area competitive for international governmental, philanthropic and industrial funding.

Of particular note, the diseases we will study include Rheumatic Heart Disease (RHD) and Peripartum Cardiomyopathy (PPCM), conditions where UCT clinical investigators have world-leading reputations and UoM investigators have highly complementary molecular and genetics expertise. These are neglected diseases of poverty which although rare in the UK have heavy impacts on population health in sub-saharan Africa. In addition to the patient benefits expected to flow from scientific discoveries made about these conditions, this programme will increase their profile with regard to research endeavour, and illustrate the practicality and productivity of a collaborative approach. This will be a beacon for future partnerships in these and other similarly neglected diseases. UK students studying with international leaders at UCT will develop deep understanding of conditions they would only rarely otherwise encounter, and gain an awareness of genomic medicine in a social context different from the UK; these will be highly valuable experiences in their future careers.

This programme will beneficially impact patients with the diseases of interest. Specifically, families in which research forming part of this programme yields a new gene discovery will benefit directly from molecular screening for diagnostic, risk stratification and prognostic purposes. More generally, establishment of an international partnership approach to personalised medicine focused on the molecularly guided use of orphan drugs will potentially lead to new treatments for some of the conditions studied. Also, molecular and genetic understanding of the mechanisms of differential susceptibility to rheumatic heart disease and peripartum cardiomyopathy will lead to more effective novel approaches to prevention and treatment.

The programme will also positively impact wider society. It will contribute to the establishment of genomic medicine in South Africa, with considerable anticipated benefits for health and economic development. The discovery of novel genes and mutations in indigenous African populations is anticipated to be particularly useful in assisting with the development of next generation therapeutics that will be of value to all world populations. Development of such therapeutics in partnership with industry will offer further opportunities for the development of African genomic science and for high added-value economic activity in Africa.

Links and contacts suitable for the prompt delivery of impact are already in place between the partners. The UCT and UoM lead applicants have worked together highly productively on genetics of cardiovascular disease since 1996. Co-applicants also have an established relationship on the genetics of retinal disorders. The Manchester Academic Health Science Centre (MAHSC; the only AHSC designated outside the South-East of England, constituted by the UoM and six NHS partners) has been a leading UK centre in respect of implementing next-generation sequencing technology to improve rates of molecular diagnosis of genetic disorders, thus the necessary infrastructure, knowledge and experience is present to deliver benefits to patients.

The UoM's Business Development Directorate actively supports PI's in their interactions with industry regarding potential novel therapeutic agents, and will be closely involved in discussions regarding potential industry partnerships that may emerge from this work.

Patient and public involvement is key to our approach and a major strength of this application: as one of several possible examples, a specifically convened patient advisory group (PAG) made instrumental contributions to the design, translation and dissemination of outcomes from the inherited retinal disease programme in Manchester; the PAG involved patients, representatives from visual impairment charities and Genetic Alliance UK, and was attended by the wider study team. The Newton programme will provide an outstanding opportunity for cross-cultural learning between the partners with regard to this critical aspect of delivering impact to our patients.