The UKZN-hosted Pharmacogenomics webinar featured renowned geneticist, Dr Manuel “George” Rebello. Image: Supplied.
By Maryann Francis
PHARMACOGENOMICS (PGx) is a field of research that analyses how the genetic makeup of an individual affects their response to drugs. For a physician, this is particularly helpful in prescribing the most effective medicine with the fewest side effects.
This was the focus of a webinar hosted by the College of Health Sciences featuring renowned geneticist Dr Manuel “George” Rebello.
The move towards precision medicine is an innovative approach that tailors disease treatment and prevention according to the genetic makeup of an individual. However, PGx also looks at the individual’s unique lifestyle information and environment to guide disease diagnosis, treatment and prevention. With environments, lifestyles and drug regimens changing constantly, ongoing research is required to enable the most effective treatment.
The term pharmacogenetics was first coined in 1959 by Friedrich Vogel.
Fatal adverse drug reactions (ADRs) are an important cause of hospital admission and the fourth or sixth leading cause of death. In addition to considerable suffering for patients and their families, suitable treatments impose high financial burdens due to the cost of lengthy hospital care. Hence, predicting serious ADRs is a priority for pharmacogenomic research.
“5-Fluorouracil is among the most widely used anticancer drugs, but a fraction of treated patients develop severe toxicity, with potentially lethal injuries,” explained Rebello. “PGx has determined a prevalence of between 3-5% among Europeans and 8% among Africans, but a staggering 12% among the South African, African population. For these patients, exposure to Fluoroucil can carry a 25-fold increased risk of treatment-related mortality, with an absolute mortality risk of up to 3.7%.”
While PGx has significant benefits in preventing ADRs, it suffers from some limitations. These include challenges on how to apply the test in clinical practice and treatment; lack of availability of the test; understanding and interpretation of evidence-based research; combining test results with other patient data for prescription optimisation; and ethical, legal and social issues.
“A PGx test can be quite expensive for the general population. A standard test costs a minimum of R3 000 and requires the interpretation of a genetics counsellor. Currently in Durban there is only one genetics counsellor based in Ampath. Tele counselling is available and is widely used by genetic counsellors across the country.
Testing using genes, drugs info and lifestyle factors is only available from Nova Genetics. Samples consisting of blood or saliva are collected and sent to these labs together with a patient request form from a general practitioner (GP) or specialist. Due to ethical reasons, the test results are not shared with the patient but with the GP.”
Professor Colleen Aldous, a geneticist at UKZN commented, “The Human Genome Project (HGP) was completed almost 19 years ago. There was enormous anticipation about what it could offer medicine, but the HGP produced more questions for us to grapple with than answers. In the past two decades, we have made some strides in precision medicine and pharmacogenomics.
“We need to get up to speed on the offerings as healthcare practitioners so that when it becomes possible to access these new innovative tools in the public health sector, we are able to offer patients better care. We also need to look at the Medical School curriculum to prepare our future doctors for these new technologies,” said Aldous.
After graduating with a BSC in Genetics from UKZN, Rebello obtained a PhD in Human Genetics from the University College London. In the course of his PhD, he worked on the Human Genome Project where he was responsible for mapping a really small part of the short arm of chromosome 9.
He has also worked on the identification of the causative gene for Retinitis Pigmentosa 17 (RP17) and a number of other projects including inherited retinal diseases, Lynch Syndrome, and the pharmacogenomics of Warfarin in South African patients.
Rebello has spent the past few years supervising postgraduate students, working on project administration, and using bioinformatics to support projects in Human Genetics at the University of Cape Town. He is involved in the start-up Genetics Laboratory - Nova Genetics, where he is the technical manager.