MRC The Gambia Projects

Learn more about the projects for each research theme at MRC Unit The Gambia.

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Coast to Coast Transcontinental Ethics Partnership

MRC The Gambia Coast to Coast - Transcontinental Ethics Partnership

Coordinator: Jonas Lexow, MRC Unit The Gambia at LSHTM
Consortium Members: Ermias Diro/Niguse Yigzam, Gondar University; Okyere Boateng, Noguchi Memorial Institute; Yohannes Sitotaw, Ministry of Science and Technology Ethiopia
Funded by: EDCTP

Independent ethical review is an essential requirement for medical research involving human participants, their biological materials or personal data. Robust review systems provide public assurance that research is carried out according to highest ethical and methodological standards, attract good quality research and drive scientific and economic development. Significant advances have been made in most Sub-Saharan African countries, yet challenges remain with embedding review in a national framework with ethics committee administration and composition and expertise of committee members.The EDCTP-funded “Coast to Coast Transcontinental Ethics Partnership” aims to address these issues by enabling a “South-South” collaboration with support of internationally recognised experts of ethics review in sub-Saharan Africa. To ensure wide applicability of the results to the region, Ethiopia, The Gambia and Ghana were selected for this coast-to-coast collaboration, representing a cross-section of sub-Saharan Africa in terms of country size and ethics review structures. The project is looking to evaluate strengths and weaknesses of the existing research ethics review systems in the participating countries. Following an initial assessment of existing structures and capacities, delegates from stakeholder institutions including a National Ethics Committee (NEC) and Research Ethics Committees/Institutional Review Boards (RECs/IRBs) will be invited to a first meeting during which assessment results will be presented and discussed. The meeting will be followed-up by a workshop to develop concrete proposals and strategies for the improvement of national and institutional review systems. Over the following year the consortium will work to implement actions and monitor progress in each country. The success of the proposed improvements will be evaluated at the end of the one year implementation phase. Outcomes and lessons learned will be discussed and translated into practical guidance that can be used as a model by other countries in the region. The “Coast to Coast Transcontinental Ethics Partnership” is expected to improve the ethics review process at national and institutional level in Ethiopia, The Gambia and Ghana, and to benefit other Sub-Saharan African countries, with positive effects for clinical research programs in this region.

Inter-generational risk factors for obesity: a path to prevention in low and middle-income countries based on a modifiable epigenetic signature in the POMC gene

Contacts: Matt Silver, Toby Candler, Andrew Prentice
Funding: MRC ING Core

Pro-opiomelanocortin (POMC) gives rise to melanocortin stimulating hormone (MSH) peptides that mediate the anorectic (appetite suppressing) action of leptin via melanocortin receptors (especially MC4R) in the hypothalamus. Mutations in the gene are associated with obesity. Increased DNA methylation at a VMR at the POMC intron2/exon3 boundary correlates with BMI in children and adults. In a Gambian cohort, we have shown that offspring methylation at the POMC VMR is correlated with mother's nutritional status (and therefore potentially modifiable) around conception. POMC VMR methylation will be measured on banked DNA, taken from children during the first 2 years of life, from a previous cohort (ENID n=800). Growth data from these cohorts (ages 0-2 years) will be examined together with DNA methylation to establish any associations between weight changes and POMC methylation. 1-year prospective study: 500 mothers and children (5-9 year old) will have monthly anthropometry and bioimpedance together with measurement of POMC VMR methylation to assess effect on nutritionally (and seasonally) driven changes in weight and body composition over a year. In addition, a subset will have DXA scans and measurement of an ab libitum breakfast. Dietary influence over POMC methylation will be examined by correlating circulating maternal one carbon metabolites and offspring methylation. Potential intergenerational influences on offspring methylation will be assessed by measuring POMC VMR methylation in 100 mother-father-offspring trios.

Infection, inflammation and hepcidin-mediated iron deficiency anaemia in African children

Contacts: Carla Cerami, Andrew Prentice
Funding: MRC

This project seeks to identify the sources of persistent low-grade inflammation in well and sick Gambian children. It will additionally try to understand the complex interacting mechanisms linking iron absorption, distribution and erythropoiesis to the effects of inflammation mediated through hepcidin, erythropoietin (EPO) and the newly discovered hormone erythroferrone (ERFE) which signals to the liver that the bone marrow requires iron. Finally we will conduct a randomised controlled trial to test whether it is possible to circumvent the hepcidin-induced blockade of iron absorption by administering iron in the form of haem. Another arm of this trial will be a proof-of-principle trial to assess the impact of reducing inflammation by co-administering azithromycin and galacto-oligosaccharides with iron. These studies, if successful, would suggest the need for a radical revision of current policies to combat IDA.

Pump Priming: Establishment of the Sub-Saharan African MuSculOskeletal Network

Contacts: Landing Jarjou, Kate Ward
Funding: GCRF, The Academy of Medical Sciences

The purpose of this grant is to facilitate inter-disciplinary partnerships between researchers in the UK and researchers in developing countries. These partnerships aim to develop high quality inter-disciplinary and innovative applications to address global challenges faced by developing countries I, for submission to other GCRF and other funding programmes.

Epigenetic mechanisms linking maternal pre-conceptional micronutrient supplementation with offspring health in India and The Gambia

Contacts: Matt Silver, Andrew Prentice
Funding: Bill & Melinda Gates Foundation

The proposed project will characterise changes in DNA methylation in blood samples from children of women who took part in two trials of pre- and peri-conceptional micronutrient supplementation in Mumbai, India and Keneba, The Gambia, and correlate methylation changes with a range of phenotypes in these children.This project offers the opportunity to test DOHaD concepts and understand underlying mechanisms within the timeframe of a single project.

Pregnancy Interventions In Mothers Relating to Diabetes In Asian India and Low-income countries (The PRIMORDIAL Study)

Contacts: Modou Jobe, Mustapha Bittaye, Andrew Prentice
Funding: MRC

The proposed study will be the first investigation to evaluate the effect of fermented yoghurt and Physical Activity (PA) initiated in early pregnancy and continued to late pregnancy on incidence of gestational diabetes (GDM) in Low- and Middle-Income Countries (LMICs). We hope to confirm that such realistic and feasible interventions are effective in preventing GDM. We will also examine the effect of such interventions on other pregnancy-related and new born outcomes. This project will build capacity for improved antenatal services in LMICs (The Gambia and India) specifically. The intervention may offer an efficient platform for future research into understanding diet and PA impact on alteration of the gut microbiota of the mother and its effects on child health. If we show that improving a mother's lifestyle during pregnancy using fermented yoghurt and PA reduces the incidence of GDM and improves metabolic health in both mother and the child, with a potential lifelong benefit, our findings will offer a scalable pathway for wide implementation.

A novel nano-iron supplement (IHAT) to safely combat iron deficiency and anemia (IDA) - 5QX0L0

Contact: Dora Pereira, Andrew Prentice
Funding: Bill & Melinda Gates Foundation

We propose to conduct a Phase II clinical trial in The Gambia to demonstrate for the first time that a novel and unique nano iron compound, which is an engineered analogue of natural food iron, SAFELY corrects iron deficiency anemia (IDA) in children in resource-poor areas. Our pre-clinical data support progressing directly to the trial proposed here, and indicate that our award-winning compound (Iron Hydroxide Adipate Tartrate: IHAT) is highly bioavailable to humans through physiologically appropriate pathways and is not available to enteric pathogens. Importantly, IHAT’s manufacture is easily scalable and has a low cost due to the facile synthesis and inexpensive GRAS raw materials.

It is our absolute conviction that IHAT has the potential to transform IDA treatment in the near future because it constitutes a paradigm-shift to what has been tested before. However, until we obtain the first clinical data supporting IHAT effectiveness it will be very challenging to secure interest from other investors.

Evaluation of MTHFR C677T genotype-dependent blood pressure response to riboflavin supplementation

Contacts: Modou Jobe, Andrew Prentice
Funding: The African Partnership for Chronic Disease Research (APCDR)

The project aims to test whether differences in BP by MTHFR genotype seen in Caucasians are exacerbated in Gambians living in a riboflavin-deplete environment; and ii) to determine whether riboflavin supplementation has genotype-differential effects on BP reduction in this population.

Neonatal iron metabolism and risk of infection

Contacts: Carla Cerami, Andrew Prentice
Funding: Bill & Melinda Gates Foundation

The Study aims to assess markers of iron metabolism among term, pre-term and small-forgestational-age infants during the early post-partum period, and to evaluate possible relationships between iron metabolism and the risk of newborn infections. In an effort to study the neonatal nutritional immunity and its role in neonatal susceptibility to infection, we will conduct an observational study in full-term, preterm and low birth weight vaginally-delivered neonates born at Serrekunda General Hospital, The Gambia.

Creating a West African BioResource for Nutritional Genetics and Epigenetics

Contacts: Prof Andrew Prentice, Dr Carla Cerami, Dr Matt Silver
Funding: MRC

The project aims to create an open access West African BioResource to interrogate the mechanisms by which genetic and epigenetic variations influence susceptibility to diet-related diseases. It will also promote innovative research designs, building for instance on the recall-by-genotype paradigm, to more efficiently and robustly explore mechanisms of diet/ (epi) genetic interactions and hence to propose next-generation health interventions.