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Developing novel therapies for leukaemia and blood disorders Gene therapy and stem cell therapy could deliver effective, affordable treatments

Researchers at AKU’s Centre for Regenerative Medicine and Stem Cell Research (CRM) are working to develop new treatments for two inherited blood disorders – beta thalassemia and sickle cell anaemia – as well as a form of blood cancer, Philadelphia chromosome-positive leukaemia. Their work is being funded by US$ 1 million from Pakistan’s Higher Education Commission and the World Bank.

Both beta thalassemia and sickle cell anaemia are the result of genetic mutations that cause their victims to suffer from a lack of haemoglobin, limiting the flow of oxygen through the body. Symptoms include fatigue and weakness, and – in the case of sickle cell anaemia – episodes of severe pain. The disorders can also have severe complications, including stroke, blindness and heart failure. Pakistan is thought to have a high incidence of beta thalassemia and sickle cell anaemia due to the prevalence of consanguineous marriage (marriages between descendants of a shared ancestor).

Treatments for the disorders include blood transfusions and bone marrow transplants, but both have drawbacks and side effects. Blood transfusion often leads to iron overload and organ damage, while bone marrow transplant is a costly, risky and invasive treatment available only to patients who can find suitable donors. Pakistan also lacks bone marrow transplant facilities and expertise, which means that most patients cannot obtain transplants.

Researchers aim to develop a genetherapy drug using CRISPR/Cas9, a gene-editing tool.

Assistant Professor Afsar Mian and his colleagues aim to use CRISPR/ Cas9, a gene-editing tool, to develop a drug that would repair the genetic defect responsible for beta thalassemia and sickle cell anaemia.

“Our goal is to deliver an innovative, less-invasive and more affordable cure for these common genetic diseases,” Professor Mian said.

Researchers will also attempt to increase the production of foetal haemoglobin in individuals with beta thalassemia and sickle cell anaemia. Adults carry small amounts of foetal haemoglobin, and higher levels are associated with milder disease in individuals with beta thalassemia and sickle cell anaemia. Increasing levels would involve using CRISPR/ Cas9 to suppress the gene that limits foetal haemoglobin production.

The chromosomal defect known as Philadelphia chromosome (Ph) leads to certain blood cells becoming cancerous. It is characteristic of two types of blood cancer: chronic myeloid leukaemia and Ph-positive acute lymphoblastic leukaemia.

While medications for these diseases exist, survival rates remain poor in patients with advanced stages of the disease due to drug resistance and side effects. CRM researchers are looking to develop a more effective treatment by engineering stem cells to deliver a peptide with therapeutic properties (the Helix 2 peptide) directly to leukaemia cells. Among other benefits, this treatment would only need to be administered once. (A peptide is similar to a protein but contains fewer amino acids.)

“We are anticipating that once introduced, the stem cells will grow and multiply in the body and continuously release the therapeutic peptide to target the cancer cells, inhibit their growth and ultimately cure the disease,” said Professor Mian, the study’s principal investigator.

Researchers hope their work will generate evidence that advances efforts to use peptides to treat other cancers.