AKU wins PKR 159 million grant

By Abdul Qadir Qureshi

(Pakistan News & Features Services)

Innovative gene editing therapies for two significant blood disorders, beta thalassemia and sickle cell anaemia, have received a boost with AKU’s Centre for Regenerative Medicine and Stem Cell Research, CRM, winning a competitive research grant of PKR159.60 million (US$ 1.02 m) to look for a genetic ‘fix’. 

Thalassemia and sickle cell disease are genetic disorders, passed down from parent to child, and are common in Pakistan. There are as many as 100,000 transfusion-dependent thalassemia patients in the country. 

Every year another 5,000 babies are born with the disorder. On the other hand, sickle-cell disease is one of the well-known causes of anaemia in Pakistan. Doctors and research scientists are aware that mutations in the haemoglobin beta-globin, HBB, gene cause both diseases. 

Patients suffer from a lack of haemoglobin, the protein that carries oxygen from the lungs to rest of the body; and a lack of oxygen in the body’s tissues can lead to poor growth, organ damage and other health problems. The only treatments available are blood transfusions or bone marrow transplants, both with drawbacks and side effects. 

Blood transfusion often leads to iron overload and organ damage. Bone marrow transplant is a costly, risky and invasive treatment available only to patients who can find suitable donors with matching blood stem cells. Also, limited bone marrow transplantation facilities and expertise within Pakistan mean that most patients cannot access this treatment.

Given these challenges, researchers around the world are looking at new gene and cell repair therapies for a treatment and potentially a cure. 

“Our research aims to find an innovative, less-invasive and more affordable cure for these common genetic diseases.Our team aspires to work on two gene editing therapies that will be applicable to both, beta thalassemia and sickle cell anaemia,” AKU’s Dr Afsar Mian, the study’s principal investigator, remarked. 

In the first approach, AKU researchers will work on developing a druggable gene editing therapy, using CRISPR/Cas9, a molecular gene editing tool. Unlike existing gene therapies, this new therapy could be injected as a drug to allow the defective part of the HBB gene to be ‘sniped’ and repaired for beta thalassemia and sickle cell disease. 

Dr Mian is excited about this research work: “Our team will be among the few researchers around the globe who are working on developing this gene editing approach. Better still, conducting this study in Pakistan will help build local capacity and solutions, instead of waiting for treatments from elsewhere.” Emergent gene and cell therapies are now seen as having the most potential to impact healthcare in the coming years. 

“This potential therapy could provide a permanent cure, bypassing the need for bone marrow transplant and blood transfusion,” Professor El-Nasir Lalani, founding director of CRM, reckoned. The second therapy involves reactivating the production of foetal haemoglobin as a substitute for the missing or faulty adult haemoglobin in beta thalassemia and sickle cell anaemia. 

Dr Mian and his team will work on gene-silencing, using the same gene editing tool and approach, suppressing the BCL11A gene that stops foetal haemoglobin from being produced. Both concepts will be first tested in the laboratory, using stem cells that have the potential to form any cell type in the body, drawn from thalassemia and sickle-cell patients. 

If successful, this will be followed by pre-clinical trials to determine if the treatment is safe. The study team includes Drs Afsar Mian, Salma Jahan, Hammad Hassan and Mohammed Yusuf from CRM and international collaborators from the University of California, San Francisco, the Norwegian University of Science and Technology and Cardiff University in the UK. 

The World Bank-supported HEC Grand Challenge Fund, launched in 2020, aims to promote research excellence in strategic sectors with awards based on competitive, peer-reviewed evaluation of proposals. CRM is one of the five winning recipients, out of more than 700 applicants in the fund's inaugural round.