BACKGROUND

In Octobetr 2017, Professor Solomon Fiifi Ofori-Acquah, Dean of the School of Biomedical and Allied Health Sciences (SBAHS), College of Health Sciences, and a prominent sickle cell disease scholar led a 32-member team of hematologists, pulmonologist, cardiologists, pediatricians, geneticists, ethicists, and basic scientists to secure a U54 Center grant of US$5.5 million from the National Institutes of Health (NIH), USA.

The team consist of investigators from nine African Universities and Research Institutes, and the University of Pittsburgh, USA developed one of the winning proposals for the Human, Hereditary and Health in Africa (H3Africa) NIH Center grants. The Office of Research, Innovation and Development (ORID), the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP) and the University of Pittsburgh’s Center for Translational and International Hematology facilitated the preparation of the application.

 

SICKLE CELL DISEASE RESEARCH IN AFRICA

Sickle cell disease (SCD) is the commonest genetic disorder in the World. It is most prevalent in Africa. This assertion led to the establishment of SickleGenAfrica: Sickle Cell Disease Genomics Network of Africa which was launched in April 20, 2018 chaired by Rev. Prof. Patrick Ayeh-Kumi, Provost for College of Health Sciences, University and Prof. Adekunle Adikile from Kuwait University at the La Palm Beach Hotel, with Prof. Ebenezer Oduro Owusu, Vice-Chancellor of University of Ghana as the key note speaker for the project launch.

The aim of the network is to build capacity locally to enable African scientists study genomics of SCD on the continent. According to Prof. Solomom F. Ofori-Acquah, who is the principal Investigator and head of the team, narrated that, the network consists of a core of investigators in nine institutions in four sub-Saharan African (SSA) countries (Cameroon, Ghana, Nigeria and Tanzania). Base on prior studies, Ofori Acquah stated that, 1.8% of births in Ghana are affected by SCD. However, Penicillin prophylaxis in neonates has reduced mortality in SCD, but in the light of this, the progress has not been matched by advancements in reducing deaths due to other causes. End-stage organ damage is now the leading cause of death among SCD patients in the West and it is self-contained to become the major cause of death in Africa once prevention and prompt management of infections becomes widely implemented on the continent. Hemolysis (destruction of red blood cell) released an Inflammatory molecules such as free heme which cause severe tissue injury that in the end causes organ damage in SCD. Again, Malaria is noted to causes severe intravascular hemolysis and potentially exacerbates hemolysis-related tissue damage in SCD unambiguously in Africa. Explaining the mechanism, Ofori-Acquah, remarked that there is a hierarchy of cytoprotective proteins that neutralize the inflammatory molecules released by hemolysis. Studies involving genetic material transfer from other species (transgenic) in SCD mice indicate some of these cytoprotective proteins such as hemopexin and heme oxygenase-1, influence cardiopulmonary and vascular dysfunctions in SCD. Ofori-Acquah and Dr. Mahmond Sani (Bayero University, Kano, Nigerian; lead for project 3) has iterated that these findings have not been validated in patients, although ‘’we have discovered wide variations in the level of several key hemolysis cytoprotective proteins among patients, suggesting that these proteins modify the clinical phenotype of SCD perhaps most strongly in Africa’’.

Their explanation indicated that, Until now, the genetics of this variation has not been defined. In addition, the functional murine (mice) studies are limited to a few organ systems, and to scientists in the West, since transgenic sickle mice colonies are not available in institutions in Africa.

With respect to the above brief concept, the studies and works of Sickle Cell Genenomics Network of Africa (SickleGenAfrica), will tackle these gaps by accomplishing seven objectives:

  • Phenotype 7, 000 SCD patients and controls in four SSA countries (That is, 7,000 SCD patients will be sample regarding phenotype);
  • Perform three collaborative genetic research project each with a functional validation study in transgenic sickle mice;
  • Establish a molecular hematology and sickle cell mouse core in Ghana;
  • Leverage an existing H3Africa biorepository to establish a SCD biorepository core in Nigeria;
  • Establish a bioinformatics core at the University of Pittsburgh to analyze the genomics data obtained by the H3Africa Center and to provide expertise to upgrade bioinformatics nodes in Ghana in partnership with H3ABionet;
  • Implement a career pipeline model to train future science leaders in Africa in blood disorders research;
  • Establish a cross cutting Administrative core enabling synergy and coordination of network activities with a robust sustainability plan for the H3Africa Center.

It is therefore to acknowledge that, The University of Ghana is submitting this application with strong institutional support from the University of Pittsburgh.

 

 

PROJECT MANAGEMENT AND FACILITATORS;

 

The SickleGenAfrica: Sickle Cell Disease Genomics Network of Africa will conduct three inter-related research projects in sickle cell disease patients in Ghana (Accra, Kumasi), Cameroon (Yaounde), Nigeria (Abuja, Lagos and Kano) and Tanzania (Dar es Salaam). Professor Ofori-Acquah will serve and provide overall oversight activity of the research, training and scientific cores of the network. He is also Lead Investigator of the primary genomics research project; a genome-wide association study of hemolysis modifying factors and their role and mechanism in acute organ damage in sickle cell disease patients. Professor Julie Makani of Muhimbili University of Health and Allied Sciences, Tanzania and Professor Awandare, Director of WACCBIP will lead the second research project focused on the genomics of severe malaria complications in sickle cell disease.

Professor Mahmoud Sani, Bayero University, Nigeria leads the third research project focused on the genomics of cardiovascular phenotypes in sickle cell disease. And Prof. Phyllis Addo (Noguchi Memorial Institute for Medical Research, now with School of Veterinary Medicine) will lead the mouse colony core.

 

The work of the team will be assisted by other University of Ghana facultym, among them includes Drs. Edeghonghon Olayemi (Department of Hematology, SBAHS), Catherine Segbefia (Department of Pediatrics, School of Medicine and Dentistry), Anita Ghansah (Noguchi Memorial Institute for Medical Research).

 

In total, Four scientific cores including a transgenic sickle cell mouse colony will be set up at the Noguchi Memorial Institute for Medical Research, which according to the investigators at the project launch will be the first of its kind in Africa. It will provide crosscutting support to the three genomics research projects. The other scientific cores include a biorepository core (for biological gene storage) in Abuja, Nigeria, and a bio-informatics core in Pittsburgh, USA, working closely with a bio-informatics node in the Kumasi Collaborative Center for Medical Research, H3ABionet in Cape Town, South Africa to process and manage the human genomics data generated by the network and an Administrative core. In addition, Clinical collaborative sites in Ghana include the Ghana Institute of Clinical Genetics, Korle Bu, Department of Child Health, Korle Bu, and the Kumasi Sickle Cell Center at Komfo Anokye Teaching Hospital.

 

FUNDING

The project is being funded by U54 Center grant of US$5.5 million from the National Institutes of Health (NIH), USA.

It is good to note that this project is being accorded similar importance and recognition by NIH synonymous to the Human Genome Sequencing Consortium popularly known as the ‘Human Genome Project (HGP)’ completed in the year 2003.

 

PROJECT RELEVANCE TO PUBLIC HEALTH.

It has been noted that approximately 2% of births in sub-Saharan Africa are affected with sickle cell disease (SCD). It’s good to note that bacteria-related deaths in SCD have reduced dramatically in children in the last 30 years in the West, and it is anticipated that a similar reduction will occur in Africa once prevention and prompt management of infections becomes widely executed on the continent. During this same schedules/period, however, the death rate among adolescents and adults with SCD has not improved largely because it cannot be predicted, prevented and effectively manage the end-stage organ damage typical of this genetic disorder. Therefore, the H3Africa network of African scientists and international collaborators will study about 7,000 children and adults with SCD in Africa to identify genetic markers/indicators associated with the development of organ damage, placing special emphasis on the body’s defense against hemolysis, a major driver of the tissue injury in SCD, with a long-term goal of helping to develop strategies to predict, prevent and treat organ damage in SCD.

It’s anticipated that this project and work work will help contribute immensely to the management and treatment of SCD whiles probably explore other relevant options such as Bone Marrow Transplant (BMT) to effectively correct the situation of SCD.

In attendance, the SickleGenAfrica launch attracted representation and leading scientists, students and other researchers from all the project collaborative centres as well as co-investigators of the project from Africa and other part of the world.

The launch of the sickle cell project was also heralded with the launch of Ghana Sickle Cell Foundation and inauguration of a 5 member board with Prof. Solomon F. Ofori-Acquah as the president and also the out dooring of the Pan-Africa Sickle Cell Foundation

Medical Journalist Association-Ghana (MJA-G), © April, 2018

A report by P.E Nukunu