$1.5m grant to AKU to boost development of innovative gene therapies

KARACHI: The Aga Khan University has received $1.5 million grant from Wellcome Leap to transform treatment of -Thalassemia and Sickle Cell Disease (SCD), which have plagued South Asia, particularly Pakistan.

These diseases have not only caused significant suffering but also a heavy economic burden on society. This grant provides a boost to development of innovative gene therapies.

Both -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, more than 70pc of marriages involve relatives. This increases chances of inheriting these genetic errors. More than 7pc of Pakistan population carries -Thalassemia gene, while the prevalence of SCD is 2pc.

Due to high carrier rates, Pakistan has 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. 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 personalised treatments or therapies developed in one country may not effectively address the unique challenges facing patients in another. Localised research is crucial to comprehend region-specific mutations and develop tailored solutions.

Dr Afsar Mian, principal investigator of the project, explains 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”.

Introduction of transplantation of genetically modified stem cells offers hope for treating -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. Prime editing, however, takes gene editing to next level”, says Dr Mian. “It offers even more precision and versatility in fixing genetic errors, reduces the chances of unintended effects, and increases effectiveness of the editing process”, he said.

The initial testing phase of this new gene editing therapy will take place in the laboratory. Stem cells with remarkable ability to develop into any cell type will be collected from Thalassemia and SCD patients.

If the tests prove successful, the next step will involve pre-clinical trials on animals. These trials will aim to assess safety of the proposed treatments before they can be tested on patients. This careful progression ensures potential therapies are thoroughly examined and meet the 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 approach offers hope and relief to a number of Thalassemia patients, paving the way for efficient solutions customised to the distinct genetic profiles of affected individuals.