Sickle cell research points to need for DNA testing

This article is supported by SIDA

[DAR ES SALAAM, SciDev.Net] Tanzanian scientists say finding gene variants that predict a sickle cell patient’s response to drugs should pave the way for DNA testing before treatment, to improve outcomes.

In their research published April in Nature, researchers at the Muhimbili University of Health and Allied Sciences (MUHAS) confirm a long-held hypothesis that a patient’s genes influence whether the drug hydroxyurea works for them.

Around a third of sickle cell patients don’t respond well to hydroxyurea, even though it’s currently the only approved drug that can significantly improve their quality of life, according to Deogratius Soka, director of the Tanzania Sickle Cell Disease Alliance, who was not involved in the study.

Sickle cell disease affects around 120 million people globally, with Africa carrying 66 per cent of the burden, according to the World Health Organization.

The inherited condition causes red blood cells to become hard, sticky, and C-shaped, triggering severe pain, organ damage, and shortened life expectancy.

Hydroxyurea helps prevent red blood cells from sickling, but many patients gain little or no benefit, explains Soka.

Being able to identify that group early, he adds, would be “a huge leap forward in improving patient care”.

Mohamed Zahir Alimohamed, a molecular geneticist and lecturer at MUHAS and co-author of the study, said the findings could be used to justify policy changes to allow for testing before administering hydroxyurea in the future.

He explained that in Tanzania, hydroxyurea is currently prescribed based on clinical criteria, such as symptoms, frequency of pain crises, and blood test results, rather than genetic testing.

“We usually monitor patients for three to six months to see if they are responding,” he said.

“That means those who do not respond can spend months on a drug that isn’t helping them.”

Lead researcher Collin Nzunda, a molecular biologist at MUHAS, says genetic testing before treatment could “boost precision medicine” in Africa by tailoring care to each patient’s genetic profile, a practice already common in wealthier countries.

The study analysed the DNA of 148 Tanzanian sickle cell patients to understand why some respond well to hydroxyurea while others do not. It found that variations in several genes were linked to treatment response.

Co-author Siana Nkya, a senior lecturer at MUHAS, says these genetic markers can predict how quickly a patient’s body processes the drug. “Someone who processes the drug slowly would need a smaller dose to avoid side effects, and vice versa,” she explains.

Nkya adds that in some cases testing could help doctors skip hydroxyurea altogether in favour of other interventions such as bone marrow transplants, new drugs in development, or even gene therapy.

She argues that in countries such as Tanzania, where treatment costs are a major barrier, this approach could have far-reaching benefits.

“It prevents unnecessary side effects, helps doctors make better treatment choices, and ultimately saves money for patients, their families, and the entire health system,” she says.

While the research is promising, the team cautions that it is still preliminary, involving a relatively small sample size.

Larger, longer-term studies are needed to validate the results before genetic testing can be rolled out nationwide.

Soka also stresses that prevention must remain a priority alongside personalised treatment. “The take-home message is therefore primary prevention, premarital screening remains the most effective means of breaking the cycle of sickle cell disease,” he tells SciDev.Net.

This article was produced by SciDev.Net’s Sub-Saharan Africa English desk.

The article is supported by Swedish International Development Cooperation Agency (SIDA, a Swedish government agency responsible for administering Sweden’s official development assistance).