Cousin marriages are a significant contributing factor to the prevalence of Thalassemia

• In Sindh, Balochistan, and Khyber Pakhtunkhwa, the practice of inbreeding marriages increases the likelihood of inherited genetic disorders, including Thalassemia

Prof Dr. Abdullah G Arijo

Thalassemia, a genetic blood disorder, has cast a long shadow over many families in Pakistan, including Sindh province. The lack of effective treatments has often left patients and their families struggling with physical and emotional pain.

However, recent advances in gene therapy are offering new hope. This innovative approach targets the root cause of the disorder by correcting the genetic anomalies that cause defective hemoglobin production. In Pakistan, where thalassemia rates are notably high, such advances could be transformative.

The Aga Khan University has received a significant grant to develop gene therapies tailored to the genetic profile of Pakistani patients. By focusing on localized research, there’s potential to address the unique challenges faced by communities in Sindh and beyond.

Such progress in gene therapy not only brings hope for a cure but also underscores the importance of continued investment in medical research, tailored healthcare solutions, and raising awareness about the benefits of early diagnosis and treatment.”

The European Medicines Agency (EMA) has recommended the approval of the first medicine utilizing CRISPR/Cas9, an innovative gene-editing technology, for the treatment of transfusion-dependent beta thalassemia and severe sickle cell disease in patients aged 12 years and older who are eligible for haematopoietic stem cell transplantation but lack a suitable donor.

Thalassemia, a hereditary blood disorder, has been a longstanding issue in Pakistan, particularly in Sindh, where a considerable segment of the population carries the β-Thalassemia gene. this disease, characterized by impaired haemoglobin production, results in severe anaemia that necessitates lifelong blood transfusions. However, recent advancements in gene therapy provide a glimmer of hope, with groundbreaking treatments such as CS-101 gene-editing therapy successfully curing patients.

Thalassemia in Sindh has remained a persistent challenge. Sindh has one of the highest Thalassemia prevalence rates in Pakistan, exacerbated by consanguineous marriages, which increase the likelihood of genetic disorders. The province faces significant challenges in managing the disease due to limited access to treatment. Blood transfusions and iron chelation therapy are costly and require continuous medical supervision. High carrier rates: Over 7% of Pakistan’s population carries the β-Thalassemia gene, leading to approximately 9,000 new cases annually. Short life expectancy: Less than 1% of patients survive beyond 20 years due to complications.

Gene therapy has emerged as a revolutionary approach to treating genetic disorders like Thalassemia. Unlike traditional treatments, which only manage symptoms, gene therapy targets the root cause by modifying defective genes. The CS-101 gene-editing therapy, developed in China, has demonstrated remarkable success in curing Thalassemia patients.

Gene therapy involves extracting hematopoietic stem cells from the patient. Editing the defective gene using advanced techniques like CRISPR-Cas9 or base-editing drugs. Reintroducing modified cells into the patient’s body restores normal hemoglobin production.

Aiza’s medical miracle story

Aiza, a 4-year-old Pakistani girl, was among the first foreign minors to receive CS-101 gene therapy in China. Previously dependent on monthly blood transfusions, she underwent the experimental treatment at Fudan University’s Children’s Hospital. Within months, her hemoglobin levels normalized, eliminating the need for transfusions. Her recovery symbolizes international cooperation and scientific progress, offering hope to thousands of families in Pakistan battling Thalassemia.

Pakistan has begun investing in gene therapy research, with institutions like Aga Khan University (AKU) receiving $1.5 million to develop innovative treatments. Researchers at AKU are exploring base editing and prime editing, which offer greater precision and fewer unintended side effects compared to traditional gene-editing techniques.

Gene therapy in Pakistan faces challenges such as high costs, regulatory barriers, and the need for localized research due to varying Thalassemia mutations. However, with ongoing investment and international collaboration, these therapies could become standard treatments in Sindh and beyond. The success of CS-101 gene therapy marks a significant milestone, bringing us closer to a future without Thalassemia. With scientific innovation and resilience, we are on the verge of a medical breakthrough that promises hope and healing for future generations.

Cousin marriages are a significant contributing factor to the prevalence of Thalassemia, particularly in communities where consanguineous unions are common. In regions such as Sindh, Balochistan, and Khyber Pakhtunkhwa, the practice of inbreeding marriages increases the likelihood of inherited genetic disorders, including Thalassemia. This higher incidence is due to the repeated transmission of recessive genes within closely related families, underscoring the importance of genetic screening and awareness programs to mitigate the risks associated with such marriages.