What is sickle cell disease?

Sickle cell disease is a group of inherited red blood cell disorders caused by a mutation in the haemoglobin gene — causing red blood cells to become rigid and sickle-shaped, obstructing blood flow and causing ischaemic organ damage. The most common form (HbSS) requires two copies of the mutant gene. It causes vaso-occlusive pain crises, anaemia, stroke, organ failure and early death without treatment.

Why does SCD kill so many African children?

In Africa, where over 80% of SCD births occur, most children still die before age 5 from complications of the disease — primarily infections (pneumococcal sepsis, malaria) and acute chest syndrome. The interventions that dramatically reduce mortality in high-income countries — newborn screening enabling prophylactic penicillin + pneumococcal vaccination; hydroxyurea; transcranial Doppler screening for stroke prevention — reach fewer than 2% of affected African children. The contrast is stark: 90%+ survival in the US (with modern care) vs <50% 5-year survival in many African settings.

What does hydroxyurea do?

Hydroxyurea is an inexpensive oral medication (generic cost approximately $0.10-0.30/day) that increases foetal haemoglobin (HbF) production — HbF prevents the polymerisation of sickle haemoglobin, reducing sickling events. The landmark MSH trial (1995) showed hydroxyurea reduces vaso-occlusive crises by 44%, acute chest syndrome by 59%, and blood transfusions, with a mortality reduction signal. It is on the WHO Essential Medicines List and is the cornerstone of SCD management, yet in sub-Saharan Africa fewer than 2% of patients receive it.

What is Casgevy and why is it historic?

Casgevy (exagamglogene autotemcel, Vertex/CRISPR Therapeutics) was approved by the FDA on December 8, 2023 — becoming the first CRISPR-based medicine ever approved for any disease in history, simultaneously with lovotibeglogene autotemcel (Lyfgenia, bluebird bio). Casgevy uses CRISPR-Cas9 to edit the patient's own haematopoietic stem cells, disabling the BCL11A gene (which suppresses foetal haemoglobin after birth) — reactivating HbF production, which prevents HbS polymerisation. One-time treatment potentially curative. Cost: approximately $2.2 million (Casgevy). The extraordinary efficacy (all trial patients eliminated severe VOCs) contrasts with the reality that 90%+ of SCD patients in Africa cannot access it.

Who can receive gene therapy?

Current SCD gene therapies require: patients aged ≥12 years (Casgevy) or ≥2 years (Lyfgenia); SCD with a history of at least 2 severe VOCs/year; adequate bone marrow function; and absence of major organ damage. The procedure involves: stem cell mobilisation, collection and editing/gene addition (laboratory phase — approximately 6 months); myeloablative conditioning chemotherapy (busulfan — destroying existing bone marrow); and infusion of the engineered cells. The entire process is highly specialised, requiring transplant centres not available in most of Africa.

What other approved treatments exist for SCD?

Beyond hydroxyurea: Crizanlizumab (Adakveo — anti-P-selectin mAb, monthly IV infusion; reduces VOC by approximately 45%); voxelotor (Oxbryta — increases HbS-O2 affinity, reducing sickling; raises Hb by approximately 1g/dL); L-glutamine (reduces oxidative stress, modest VOC reduction). Transfusion therapy: regular exchange transfusions for stroke prevention and management. Allogeneic HSCT: curative with matched sibling donor — but few patients have an HLA-matched sibling, and procedure-related mortality risk is approximately 5%.

How does malaria interact with SCD?

Sickle cell trait (HbAS — heterozygous carrier) provides approximately 50-90% protection against severe malaria — explaining why the HbS mutation persisted in Africa despite its devastating homozygous effects (balanced polymorphism). For people with SCD (HbSS), malaria is particularly dangerous — triggering massive haemolysis, sickling crises and acute chest syndrome. Malaria prevention (bed nets, prophylaxis) is a critical component of SCD management in endemic settings. This HbS-malaria interaction was one of the first demonstrations of evolutionary pressure from infectious disease on human genetics.

How does GMJ News cover sickle cell disease?

GMJ News covers WHO SCD data, Casgevy and Lyfgenia approvals, hydroxyurea access crisis in Africa, newborn screening equity, crizanlizumab and voxelotor, and the SCD-malaria interaction. SCD is a major health equity issue — the treatment gap between Africa and high-income countries exemplifies global health inequity at its starkest.

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Sickle Cell Disease

Q: What does hydroxyurea do?

Hydroxyurea is an inexpensive oral medication (generic cost approximately $0.10-0.30/day) that increases foetal haemoglobin (HbF) production — HbF prevents the polymerisation of sickle haemoglobin, reducing sickling events. The landmark MSH trial (1995) showed hydroxyurea reduces vaso-occlusive crises by 44%, acute chest syndrome by 59%, and blood transfusions, with a mortality reduction signal. It is on the WHO Essential Medicines List and is the cornerstone of SCD management, yet in sub-Saharan Africa fewer than 2% of patients receive it.

Q: What is Casgevy and why is it historic?

Casgevy (exagamglogene autotemcel, Vertex/CRISPR Therapeutics) was approved by the FDA on December 8, 2023 — becoming the first CRISPR-based medicine ever approved for any disease in history, simultaneously with lovotibeglogene autotemcel (Lyfgenia, bluebird bio). Casgevy uses CRISPR-Cas9 to edit the patient's own haematopoietic stem cells, disabling the BCL11A gene (which suppresses foetal haemoglobin after birth) — reactivating HbF production, which prevents HbS polymerisation. One-time treatment potentially curative. Cost: approximately $2.2 million (Casgevy). The extraordinary efficacy (all trial patients eliminated severe VOCs) contrasts with the reality that 90%+ of SCD patients in Africa cannot access it.

Q: Who can receive gene therapy?

Current SCD gene therapies require: patients aged ≥12 years (Casgevy) or ≥2 years (Lyfgenia); SCD with a history of at least 2 severe VOCs/year; adequate bone marrow function; and absence of major organ damage. The procedure involves: stem cell mobilisation, collection and editing/gene addition (laboratory phase — approximately 6 months); myeloablative conditioning chemotherapy (busulfan — destroying existing bone marrow); and infusion of the engineered cells. The entire process is highly specialised, requiring transplant centres not available in most of Africa.

Q: What other approved treatments exist for SCD?

Beyond hydroxyurea: Crizanlizumab (Adakveo — anti-P-selectin mAb, monthly IV infusion; reduces VOC by approximately 45%); voxelotor (Oxbryta — increases HbS-O2 affinity, reducing sickling; raises Hb by approximately 1g/dL); L-glutamine (reduces oxidative stress, modest VOC reduction). Transfusion therapy: regular exchange transfusions for stroke prevention and management. Allogeneic HSCT: curative with matched sibling donor — but few patients have an HLA-matched sibling, and procedure-related mortality risk is approximately 5%.

Q: How does malaria interact with SCD?

Sickle cell trait (HbAS — heterozygous carrier) provides approximately 50-90% protection against severe malaria — explaining why the HbS mutation persisted in Africa despite its devastating homozygous effects (balanced polymorphism). For people with SCD (HbSS), malaria is particularly dangerous — triggering massive haemolysis, sickling crises and acute chest syndrome. Malaria prevention (bed nets, prophylaxis) is a critical component of SCD management in endemic settings. This HbS-malaria interaction was one of the first demonstrations of evolutionary pressure from infectious disease on human genetics.

Q: How does GMJ News cover sickle cell disease?

GMJ News covers WHO SCD data, Casgevy and Lyfgenia approvals, hydroxyurea access crisis in Africa, newborn screening equity, crizanlizumab and voxelotor, and the SCD-malaria interaction. SCD is a major health equity issue — the treatment gap between Africa and high-income countries exemplifies global health inequity at its starkest.

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Sickle cell disease — the most common serious genetic disorder globally — affects approximately 8 million people worldwide with approximately 300,000 affected babies born every year, over 80% in sub-Saharan Africa, from a point mutation in the haemoglobin beta-chain gene that causes red blood cells to deform into rigid sickle shapes, obstructing blood flow and causing vaso-occlusive crises, organ damage, stroke and early death (WHO). December 2023 marked a historic milestone: the FDA simultaneously approved two gene therapies — exagamglogene autotemcel (Casgevy, the first CRISPR-based medicine ever approved for any disease) and lovotibeglogene autotemcel (Lyfgenia) — potentially offering functional cure; yet both cost approximately $2-3 million per patient, making them inaccessible to the 90%+ of patients in Africa.

Key messages

300K births/year — 80% in Africa

300,000 babies with sickle cell disease are born every year globally — over 80% in sub-Saharan Africa, where access to the simple, inexpensive treatment hydroxyurea remains critically limited (WHO).

First CRISPR medicine — Casgevy 2023

December 2023: FDA simultaneously approved exagamglogene autotemcel (Casgevy — first CRISPR therapy ever approved for any disease) and lovotibeglogene autotemcel (Lyfgenia) for SCD — potentially curative but at $2-3 million per patient, inaccessible to the 90%+ of patients in Africa.

Hydroxyurea — cheap, effective, underused

Hydroxyurea — an inexpensive, oral medication that increases foetal haemoglobin (HbF), reducing sickling — is on the WHO Essential Medicines List and dramatically reduces vaso-occlusive crises, acute chest syndrome and mortality. Yet in Africa, where 80% of SCD patients live, it reaches fewer than 2% of those who need it.

Vaso-occlusive crisis — the hallmark

Sickle cells obstruct small blood vessels, causing ischaemic pain (vaso-occlusive crisis — VOC) in bones, chest, abdomen and joints. Acute chest syndrome (ACS) — pulmonary sickling — is the most common cause of death in SCD and a medical emergency.

Newborn screening saves lives

Newborn screening enables diagnosis before the first sickling event — allowing prophylactic penicillin, pneumococcal vaccination and hydroxyurea to prevent early childhood deaths. Where newborn screening is established, SCD child mortality falls dramatically.

Allogeneic stem cell transplant

Matched sibling donor allogeneic haematopoietic stem cell transplantation (HSCT) has been the established curative option for SCD — but requires an HLA-matched sibling (available in approximately 10-15%) and carries procedure-related mortality. Gene therapy eliminates the need for a matched donor.

Key statistics

~8M

people living with SCD globally

WHO

300K

SCD births/year globally

WHO

>80%

of SCD births in sub-Saharan Africa

WHO

<2%

of African SCD patients receive hydroxyurea

WHO/research

$2-3M

cost of approved gene therapies per patient

FDA/Vertex/bluebird

Dec 2023

first CRISPR medicine (Casgevy) approved by FDA

FDA

SCD births per year by region (% of global) — WHO

Source: WHO. Sub-Saharan Africa carries the vast majority of the SCD birth burden.

Glossary of key terms

HbS (sickle haemoglobin)
WHOA point mutation in the HBB gene (Glu→Val at position 6) causing haemoglobin to polymerise under low-oxygen conditions — deforming red blood cells into rigid sickle shapes. Homozygous HbSS (the most severe form) has the highest disease burden. Other genotypes: HbSC, HbS/β-thal.

Hydroxyurea
WHO EMLAn oral myelosuppressive agent that increases foetal haemoglobin (HbF) levels — HbF prevents HbS polymerisation, reducing sickling. Reduces vaso-occlusive crises by approximately 44% (MSH trial); reduces ACS and mortality. Cheap (pennies/day for generic); on WHO EML; tragically underutilised in Africa.

Acute chest syndrome (ACS)
WHO/ASHA life-threatening SCD complication — new pulmonary infiltrate + respiratory symptoms (fever, chest pain, hypoxia) caused by sickling in pulmonary vasculature, fat embolism or infection. The most common SCD cause of death and the most common cause of ICU admission. Treated with exchange transfusion, oxygen, incentive spirometry, antibiotics.

Exagamglogene autotemcel (Casgevy)
FDA Dec 2023The first CRISPR-based human medicine — editing the patient's own haematopoietic stem cells to reactivate foetal haemoglobin (HbF) production by disrupting the BCL11A gene (a γ-globin silencer). FDA approved December 8, 2023 for SCD and β-thalassaemia. Single infusion after myeloablative conditioning.

Vaso-occlusive crisis (VOC)
WHO/ASHAcute ischaemic pain from microvascular obstruction by sickled red blood cells — the hallmark of SCD. Affects bones (most common — long bones, vertebrae, ribs), chest, abdomen and other organs. Managed with opioid analgesia, hydration, oxygen.

Crizanlizumab
FDA/EMAA monoclonal antibody targeting P-selectin — an adhesion molecule on endothelial cells and platelets that mediates sickle cell adhesion to the vessel wall. Reduces VOC rate by approximately 45% (SUSTAIN trial). Monthly IV infusion.