AKU received a grant of 159 crore rupees for the development of gene editing therapies for the treatment of blood diseases

The AKU Center for Regenerative Medicine and Stem Cell Research (CRM) has promoted innovative gene editing therapies for two major blood diseases (β-thalassemia and sickle cell anemia), winning a competition of 159.6 million rupees ($1.02 million) Research funding to find genetic “repair”.

Thalassemia and sickle cell disease are genetic diseases that are passed from parents to children and are common in Pakistan. There are as many as 100,000 thalassemia patients across the country who rely on blood transfusions. Every year another 5,000 babies are born with this disease. On the other hand, sickle cell disease is one of the well-known causes of anemia in Pakistan.

Doctors and research scientists realize that mutations in the hemoglobin beta-globin HBB gene can cause these two diseases. Patients lack hemoglobin, a protein that transports oxygen from the lungs to other parts of the body; hypoxia in body tissues can lead to poor growth, organ damage, and other health problems.

The only treatment available is blood transfusion or bone marrow transplantation, both of which have disadvantages and side effects. Blood transfusions usually cause iron overload and organ damage. Bone marrow transplantation is an expensive, risky, and invasive treatment that is only suitable for patients who can find a suitable donor with matching hematopoietic stem cells. In addition, Pakistan’s limited bone marrow transplant facilities and expertise mean that most patients cannot access this treatment.

In view of these challenges, researchers around the world are looking for new gene and cell repair therapies to treat and potentially cure.

“Our research aims to find an innovative, less invasive, and more affordable treatment for these common genetic diseases,” said the lead researcher of the study, Dr. Afsar Mian of AKU. “Our team is eager to study two gene editing therapies, which will be suitable for beta thalassemia and sickle cell anemia.” In the first method, AKU researchers will use the molecular gene editing tool CRISPR/Cas9 to develop a Drug gene editing therapy. Unlike existing gene therapy, this new therapy can be injected as a drug to allow the defective part of the HBB gene to be “cut out” and repair beta thalassemia and sickle cell disease.

Dr. Mian is excited about this research work: “Our team will become one of the few researchers in the world dedicated to developing this gene editing method. Better yet, conducting this research in Pakistan will help To build local capabilities and solutions instead of waiting for treatment elsewhere.”

Now, emerging gene and cell therapies are considered most likely to affect healthcare in the next few years. “This potential therapy can provide a permanent cure without bone marrow transplantation and blood transfusion,” said Professor El-Nasir Lalani, the founding director of CRM. The second treatment involves reactivating the production of fetal hemoglobin to replace the missing or defective adult hemoglobin in beta thalassemia and sickle cell anemia. “

Dr. Mian and his team will work on gene silencing, using the same gene editing tools and methods to inhibit the BCL11A gene that prevents fetal hemoglobin production.

These two concepts will first be tested in the laboratory, using stem cells that are likely to form any cell type in the body. These stem cells come from thalassemia and sickle cell patients. If successful, preclinical trials will follow to determine whether the treatment is safe.

The research team includes Afsar Mian, Salma Jahan, Hammad Hassan, and Dr. Mohammed Yusuf from CRM, as well as international collaborators from the University of California, San Francisco, Norwegian University of Science and Technology, and Cardiff University, UK.

The HEC Grand Challenge Fund supported by the World Bank was launched in 2020 and aims to promote research excellence in strategic areas through competitive, peer-reviewed proposal evaluation rewards. CRM is one of five winners out of more than 700 applicants for the fund’s first round of financing.