IBADAN, Nigeria — In October, the U.S. National Institutes of Health and the Bill & Melinda Gates Foundation announced plans to invest $200 million in the development of gene-based cures for sickle cell disease and HIV.
“We are expected to die young, so we spend our lives trying to prove them wrong.”— Shola Akindipe, a 24-year-old Nigerian with sickle cell disease
Africa is the worst-affected region by both diseases. But while the prevalence of HIV is reducing across the continent and more HIV-positive Africans are receiving treatment, the outlook for sickle cell disease remains grim. In sub-Saharan Africa, the inherited blood disorder is thought to be the underlying cause of about 1 in 12 newborn deaths, and the number of babies born with it each year is growing.
Every year, approximately 15,000 babies in Ghana are born with sickle cell disease. But treatment exists, and early diagnosis through newborn screening could significantly reduce preventable deaths.
The last major innovation in the management of sickle cell disease came in the 1980s, with the discovery that a drug called hydroxyurea could reduce pain for people living with it. Beyond that, efforts have been focused mostly on prevention, rather than treatment for people already living with the disease.
Now, though, a new wave of innovation is bringing hope to those affected.
Sickle cell disease is difficult to cure. Arising from a genetic mutation — which usually must be inherited from both parents — it causes the body to continuously produce blood cells that contain an error in the hemoglobin, the protein that delivers oxygen around the body.
The options for a cure are either to correct the error in every cell or to change the individual's blood system. The latter has been attempted via bone marrow transplants, with limited success.
Instead, efforts to tackle sickle cell disease have focused on educating the public about the importance of knowing their genotype and understanding the risk of passing the disease on to children.
For example, many religious organizations in Africa require engaged couples to present a doctor’s report confirming their genotypes, either discouraging marriage or outright refusing to conduct it if both partners are carriers.
“Religious organizations have become our major partner in ending sickle cell disease in Ghana,” Dr. Nsiah Asare, adviser to the president of Ghana on health, told Devex. Some local governments have even made genotype testing a legal requirement before a couple can marry.
Beyond simple efforts like this, however — which are often ethically and socially fraught — the fight against sickle cell disease has been largely stagnant in most African countries. With few treatment options available, people living with the disease face life-threatening daily struggles, including severe pain and vulnerability to infections.
Timileyin Edwin, founder of the Nigeria-based Crimson Bow Sickle Cell Initiative, is one of them. “Apart from the physical challenges, emotional challenges might arise because some warriors [people living with sickle cell disease] are tired of experiencing pain, being burdens, or even having to live life with limitation.”
“Stigma is another challenge … [alongside] the quality of health care service most sickle cell patients have access to. Good-quality specialized health care is expensive,” Edwin said.
Technology to the rescue?
Despite the limited progress made so far, the Gates Foundation is now betting on a gene-based cure for sickle cell disease. “That would mean repairing or compensating for the mutations in hemoglobin,” Bryan Callahan, a spokesperson for the foundation, said.
Previously regarded as experimental, gene therapy has rapidly evolved. A September 2019 review by a team of scientists in Germany and Iran noted that at least 20 gene therapy products have already been approved.
“We believe that the goal of developing gene-based, single-infusion cures for sickle cell disease is achievable and could transform the lives of millions,” Callahan said. “Gene-based technologies are a rapidly evolving field that [holds] enormous promise. We are at a pivotal juncture with the technology where we can now say that a focused, aligned effort with strong leadership from NIH and the Gates Foundation, working in collaboration with other critical partners, could bring the change that has been long sought.”
If gene-based cures do emerge, they could drastically change the lives of patients with the disease. But there is another major challenge: the difficulty of diagnosing it in newborns, meaning many die or suffer unnecessarily before they can be treated.
The gold standard method for diagnosis across many African countries is hemoglobin electrophoresis, but this requires expertise and uninterrupted electricity, among other factors that mean it is hard to make reliably available in resource-limited settings.
So health startup Hemex developed a solution that is being tested in a number of African countries to screen for sickle cell disease. Called Gazelle, it is a miniaturized version of the gold standard test. Administration requires minimal training and results can be displayed in less than 10 minutes.
Hemex CEO Patti White said the basis for the technology is a standard fundamental that has been used since the 1940s but has now advanced with modern capabilities. She said that while the race to end sickle cell disease in Africa has historically been slow and challenging, there is now a glimmer of light in emerging innovations.
“We have experienced many amazing changes already in our lifetime, and it seems like there is now starting to be enough critical mass for sickle cell disease. There was not enough [even] four years ago when we started,” she told Devex.
Finally, there is the access challenge: Even when new drugs and innovative testing solutions become available, they often don’t reach low-income patients living in hard-to-reach areas.
In Ghana, drone delivery company Zipline is working with partners in hopes of finding a solution. Although the possibilities have so far only been demoed, head of health care partnerships Dhruv Boddupalli said the service could be used to make sure screening tests, medicines, and equipment are widely available and that adult and pediatric patients can receive the care they need close to home.
“By delivering medicines on demand to any health facility, we reduce unnecessary transfers and referrals,” Boddupalli said.
Time is ticking
The wave of innovation in the diagnosis and treatment of sickle cell disease could vastly improve the quality of life for Africans living with it — but it will take time. The Gates Foundation would not say how soon a gene-based cure might become available, saying only that its investments “will aim to build on existing infrastructure to accelerate research on gene-based treatments.”
And aside from Ghana, where newborn screening for sickle cell disease is being intensified, aggressive efforts to improve access to diagnosis and treatment are scarce.
Patrice Matchaba, group head of global health at pharmaceutical giant Novartis, argued that a more realistic approach in the shorter term would be a comprehensive and early deployment of existing tools, including screening and hydroxyurea. This approach is being piloted in Ghana by a consortium of partners led by the government and Novartis.
He noted that an overall improvement in Africa’s primary health care system would make a significant difference. “Only 2 to 4% of newly born babies are screened for sickle cell disease in Africa. ... We can save so many lives in Africa just by testing all newborns” and providing them with the right treatments, Matchaba said.
But the reality for most sickle cell patients in Africa is that they cannot afford or do not have access to these services. Hydroxyurea, for example — which is the most commonly used treatment for sickle cell patients in higher-income countries — is only registered for the management of sickle cell disease in two African countries: Ghana and Uganda.
Realizing the reality of the situation they are dealing with and the unclear road to a permanent respite, Africans living with sickle cell disease said that for now, all they can do is try to overcome the limitations.
“Many times when people find out that I am living with sickle cell disease, the first thing that subconsciously comes out of their mouth is, ‘Someone I knew also died of the disease’,” said Shola Akindipe, a 24-year-old Nigerian.
“We are expected to die young, so we spend our lives trying to prove them wrong. But when you don’t have enough money to pay for good health care and medicines, [then] society’s expectations will come to pass.”