This story has been updated to include additional comments from the researchers.
Researchers from the University of Cape Town and the Center for Proteomic and Genomic Research in South Africa said last week that they plan to take part in the Pharmacogenomics for Every Nation Initiative.
The two parties will form a South African PGENI Center of Competence for conducting translational research relevant to the local burden of disease that will aim to identify the most appropriate drugs for treating diseases in African populations, they said.
PGENI is an initiative of the Institute of Pharmacogenomics and Individualized Therapy at the University of North Carolina. Members of the initiative work to integrate genetic risk data for an individual country and World Health Organization essential-medicine recommendations into public-health decision making. PGENI has similar regional centers in Brazil, Jordan, South Africa, India, China, Mexico, and Ghana, and is active in 100 countries worldwide.
The South African researchers plan to use Affymetrix's DMET Plus product to investigate the prevalence of specific SNPs in southern African populations and the relationship of such traits with drug efficacy.
Using DMET Plus, researchers can screen samples against 1,936 drug metabolism markers in approximately 230 genes. Affy has sold the panel for drug metabolism studies since 2008 (BAN 1/29/2008).
Reinhard Hiller, managing director of the CPGR, told BioArray News that the center selected DMET Plus because it is "well suited to generating high-quality pharmacogenetic data sets" that can be translated into "practical applications with a tangible benefit for the community."
Hiller noted that DMET Plus was developed in collaboration with Affy's partners in the pharmaceutical industry. "The data we are going to provide will create a useful reference for corporate drug developers who are well aware of the concept of pharmacogenomics and its implications on drug development," he said.
Regarding other technologies, Hiller said it is "conceivable" that the researchers will use "medium- to high-throughput next-gen sequencing to generate more in-depth information on the DNA level about drug related genetic traits in indigenous populations."
He added that it is also likely that the researchers will use high-throughput PCR systems for validation or assay development purposes.
The CPGR is positioned to offer a variety of technologies to the project as needed. The specialist not-for-profit contract research organization was established in 2006 to provide support and services to the South African life science and biotech community (BAN 5/29/2007). The center began offering services on Affy's GeneChip platform in 2008 (BAN 10/7/2008).
A 'Particular Problem'
According to the researchers, side effects in drug treatments present a "particular problem" in developing nations like South Africa because most drugs have been developed for use in Caucasian populations and therefore don't account for the genetic makeup of other population groups. Such side effects "create a significant financial burden" for healthcare systems in developing nations, they said in a statement.
Because of these issues, the planned South African PGENI Center will initially concentrate on investigating the prevalence of SNPs with known implications in drug efficacy using DMET Plus. An initial pilot study of a "few hundred samples" is envisioned, followed by "large-scale studies," with an aim to eventually generate data sets from thousands of individuals. These will ultimately be used to determine drug-specific SNP profiles and to develop recommendations for policy makers and healthcare providers to improve the efficacy of drug treatments in South Africa.
Hiller said that initially samples will be collected in South Africa, covering the "major southern African populations." Study planning and recruitment will be coordinated by UCT. He said that early studies will number in the hundreds of samples, but said that PGENI "aims for large-scale studies including up to tens of thousands of individuals per geographical area."
To accomplish that, the researchers will look beyond South Africa.
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"The vision is to work with researchers across the African continent," Raj Ramesar, professor of human genetics at UCT and scientific director of the PGENI Center in South Africa, told BioArray News this week.
One vehicle for doing that could be the Human Heredity and Health in Africa Initiative, which aims to establish networks of African investigators to the study of genomics and environmental determinants of common diseases with the ultimate goal of improving the health of African populations. Called H3Africa, the initiative is being led by the African Society of Human Genetics, the US National Institutes of Health, and the Wellcome Trust in the UK.
Ramesar said that a range of genomics and health research initiatives across the continent are being planned. "Even if pharmacogenomics is not one of the supported initiatives, this kind of vehicle may provide the reach and networking that is going to be required for our pharmacogenomic initiative," he said.
According to Ramesar, South Africa is ready for such a pharmacogenomics project because the country currently imports drugs from international vendors and uses them to treat symptoms or diseases for which it "presumes biological processes are the same between our populations, and where the drugs were originally manufactured and trialed."
He said that gaining more insight into how African populations metabolize different drugs could have an impact on local healthcare. "It is understandable that African populations, which are most ancient, and carry the greatest [amount] of genomic variation, are also expected to carry a range of mutations in these relevant genes involved in pharmacogenetics, which may not be apparent in other populations," Ramesar said.
He added that South African researchers have "clear evidence" that a range of drugs designed to work optimally in European populations, may not do so in Africa's indigenous populations.
Ramesar said that the researchers ultimately hope to be able to make recommendations that "optimize drug use for specific diseases according an individual’s ability to process such drugs optimally."
Under Ramesar's leadership, the division of human genetics at UCT has concentrated on clinical service delivery, through medical genetics clinics at affiliated hospitals. More recently, it has focused its attention to studying genomic variation in indigenous African populations and relating such variations to disease predisposition and response to therapeutics.
Ramesar said he hopes that the findings of the PGENI will eventually be taken into account by drug makers.
"Practically everybody going into a clinic comes out of the clinic with some sort of drug," said Ramesar. "It is reasonably clear that genomics, while considered to be important for and by genomics people, has not had much uptake from the run-of-the-mill clinical fraternity," he said.
According to Ramesar, drug developers are "very keen" on seeing clinical relevance and utility. "If they know that some drugs work extremely well and others don't in a specific population, they will also want to know the biological basis for this," he said. "If they see genetics as a vehicle for this … they will reach out for this information, and be part of the advocacy which is required for genetics."
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