Aga Khan University Receives $1.5 Million Boost to Revolutionize Treatment of β-Thalassemia and Sickle Cell Disease

Aga Khan University has received a $1.5 million grant from Wellcome Leap, a leading global health innovation organization. This significant grant will support a project that seeks to transform the treatment of β-Thalassemia and Sickle Cell Disease (SCD), which have plagued South Asia, particularly Pakistan. These diseases have not only caused significant suffering but also imposed a heavy economic burden on society. This competitive grant provides a significant boost to the development of innovative gene therapies.

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Both β-Thalassemia and SCD are hereditary conditions, arising from genetic anomalies affecting the production of hemoglobin, a vital protein responsible for transporting oxygen in our bloodstream. In Pakistan, where many marriages occur within families (such as cousins), more than 70% of marriages involve relatives. This increases the chances of inheriting these genetic errors. In Pakistan, more than 7% of the population carries the β-Thalassemia gene, while the prevalence of SCD is estimated to be 2%. Due to these high carrier rates, Pakistan has a large population of over 100,000 registered Thalassemia patients with approximately 9,000 children born with the severe form known as Thalassemia Major. Treatment of these patients is significantly costly, requiring frequent blood transfusions and iron chelation therapy. Sadly, the current treatment options are challenging to sustain, with less than one percent of patients surviving beyond the age of 20.

Thalassemia varies worldwide, with over 300 different mutations in various regions, including Pakistan. Due to this diversity and the increasing focus on personalized treatments or therapies developed in one country may not effectively address the unique challenges faced by patients in another. Thus, localized research is crucial to comprehend region-specific mutations and develop tailored solutions.

Dr Afsar Mian, Assistant Professor at Aga Khan University, and the principal investigator of the project, explains the limitations of the only known curative therapy, allogenic hematopoietic stem cell (HSC) transplantation, which is dependent on donor compatibility, expensive and can result in treatment failure. Dr Mian states, “This limits access to treatment and highlights the need for alternative therapies.”

In recent years, the introduction of transplantation of genetically modified stem cells offers hope for treating β-Thalassemia and SCD. Recent advancements in gene editing technologies such as CRISPR-Cas9, offer hope to correct genetic mutations. This involves editing stem cells taken from patients using CRISPR-Cas9 before transplanting into the same patient. The research team at AKU aims to explore two advanced gene editing techniques: base editing and prime editing. These techniques have gained popularity due to their precision, specificity, and minimal unintended side effects compared to CRISPR-Cas9 technology.

“CRISPR is a remarkable technology that allows scientists to make changes in our DNA. However, prime editing takes gene editing to the next level,” says Dr Mian. “It offers even more precision and versatility in fixing genetic errors, reduces the chances of unintended effects, and increases the effectiveness of the editing process.”

The initial testing phase of this new gene editing therapy will take place in the laboratory, where stem cells with the remarkable ability to develop into any cell type will be collected from Thalassemia and SCD patients. If laboratory tests prove successful, the next step will involve pre-clinical trials on animals. These trials will aim to assess the safety of the proposed treatments before they can be tested on patients. This careful progression from laboratory testing to pre-clinical trials ensures that the potential therapies are thoroughly examined and meet the necessary safety standards before further advancement.

The study team at AKU includes Dr Afsar Mian, Dr Salman Kirmani, Dr Ambreen Fatima, Dr Fawad Ur Rehman, and Dr Irfan Hussain.

This groundbreaking approach offers newfound hope and relief to a significant number of Thalassemia patients, paving the way for targeted and efficient solutions customized to the distinct genetic profiles of affected individuals.