One may wonder why a family with a sickle cell child endures unending trips to the hospital. This child often experiences painful episodes known as “vaso-occlusive crises” (VOC) and is more susceptible to infections due to damage in organs vital for immunity, such as the spleen. As for why I’ve used the term “sickle cell child” instead of “patient,” well, let’s leave that as a story for another day.
Sickle Cell Disease (SCD) is a genetic disorder affecting haemoglobin, the oxygen-carrying molecule in red blood cells. In individuals with SCD, red blood cells take on a rigid, crescent moon shape instead of the smooth, flexible disc shapes seen in healthy cells. This rigidity causes the cells to block blood vessels, disrupting normal blood flow and leading to painful VOC episodes and potential organ damage.
Globally, the burden of SCD stands at 120 million people, with Africa alone accounting for 66 per cent of global sickle cell cases. Tanzania ranks among the highest in Africa, with an estimated 11,000 children born with SCD annually, just a few ranks behind Nigeria – known as “the sickle cell capital.” India, Congo, and Angola are also among the countries with the highest rates of sickle cell disease.
The treatment for this hapless condition ranges from managing symptoms to a potential cure to lighten or even reverse the lifestyle of affected individuals. SCD treatment includes pain relief medications, blood transfusions, and hydroxyurea therapy, increasing fetal haemoglobin to subside the mutated dysfunctional adult haemoglobin.
Although effective for many patients, unfortunately, some individuals don’t respond to hydroxyurea therapy. Bone marrow transplant is considered a functional, sure solution. However, it depends on finding a perfectly matched donor to provide healthy regenerative stem cells for the SCD patient. Following stem cell transplants, genetic therapies are within the arsenal that can potentially cure SCD.
Genetic therapies
Genetic therapies are still novel, and so they could be considered the new kid on the block. Genetic therapy for genetic disorders, particularly SCD, is a medical treatment that changes a patient’s genes to treat a condition. Specifically, it targets the default disease-causing gene(s), and modifications occur by replacing the disease-causing gene with a functional copy of the gene or by inactivating the disease-causing gene that is not functioning properly.
The magic of gene therapy in sickle cell treatment is that it uses the patient’s own stem cells, thus overcoming donor rejection issues faced in stem cell transplants. This therapy alleviates the patient’s need for frequent transfusions, frees them of painful episodes, and likely increases adequate haemoglobin levels in the blood. While gene therapy may not be regarded as the ultimate “cure” for sickle cell disease, one can only imagine its profound relief and life-changing benefits to those who receive it.
In 2023, the FDA approved two groundbreaking gene therapies to treat sickle cell disease: Exagamglogene autotemcel and Lovotibeglogene autotemcel. It was a privilege to interview Jimi Olaghere, a beneficiary of one of these life-changing treatments.
Jimi’s inspirational journey showcases how his life improved profoundly post-therapy. He even reached new heights and summited Mount Kilimanjaro! His achievement set the world record for being the first sickle cell patient to reach Africa’s tallest point: 19,341 feet above sea level.
Jimi’s journey began as a desperate search for a cure. With hydroxyurea no longer effective, his desire to live freely, build a family, and escape the hospital bed drove him to enrol in a clinical trial by Vertex Pharmaceuticals and CRISPR Therapeutic’s Exagamglogene autotemcel (Casgevy) for gene therapy in 2019. Post-therapy, Jimi testified to increased boundless energy, no pain, and freedom from hospitalisation.
Reflecting on his experience climbing Mount Kilimanjaro, he acknowledges the physical demands of the journey. Still, after months of rigorous preparation and a significant boost in his health post-treatment, he found it entirely worthwhile. For someone with SCD, undertaking such an energy-intensive challenge was once unimaginable, making his accomplishment even more extraordinary.
Challenges to tackle
Despite the enormous benefits of genetic therapy, it’s no secret that it is inaccessible. The cost of already licensed gene therapies is extremely high, and they are even less available to lower- and middle-income countries (LMICS).
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At the moment, access to gene therapy is exclusively through managed access, clinical trials, and compassionate programmes, according to an article entitled Accessing Gene Therapy in LMICs published in a Molecular Therapy journal. Speaking to Jimi, he acknowledges the global inaccessibility and advocates for healthcare reforms and cost-effective manufacturing strategies globally.
It is undeniable that Tanzania and the African region at large still face significant challenges in addressing SCD. Identifying the burden of SCD and improving early detection through prenatal and newborn screening are essential first steps.
Public education is another pivotal area, particularly in raising awareness about genetic screening and ensuring a deeper understanding of the disease. This would help reduce stigma, create supportive environments, and empower communities to support those living with SCD.
To prepare for transformative treatments like gene therapy, African countries must invest in the infrastructure required for advanced healthcare delivery. This includes building local research capacity, as exemplified by Dr Siana Nkya’s groundbreaking studies on genetic factors influencing fetal haemoglobin levels in SCD patients in Tanzania. This will pave the way for tailored interventions and highlight the importance of equipping researchers with resources and mentorship.
It might seem like a long journey before genetic therapy becomes easily accessible, but every small step towards that goal is far more valuable than standing still. Drawing from Jimi’s message, global health leaders and stakeholders must prioritise reducing manufacturing costs by adopting innovative approaches such as point-of-care production and more affordable mobilisation and delivery methods.
Enabling regions to develop and produce these therapies locally will ensure that lifesaving treatments are both accessible and sustainable for continents most burdened by sickle cell disease.
Rachel Mtama is a research officer with the Tanzania Human Genetics Organization (THGO), a non-governmental organisation coordinating human genetics research and activities in the country. She’s available at rachelmtama2018@gmail.com or on X at @mtamajr.
