On this year’s International Thalassemia Day (May 8), the beta-thalassemia community is hopeful that advances in gene therapy may lead to new treatment options. While Dr. Antonio Piga from the San Luigi Gonzaga University Hospital in Torino, Italy, shares that hope, he believes gene therapy remains distant.
“Even with recent advances, gene therapy approaches for beta-thalassemia are less than perfect,” Piga said. “Gene therapy may be a viable treatment for a majority of patients in 20 years. But what do we do until then? What if we could correct the downstream process that is broken in beta-thalassemia?”
That process is the production of healthy red blood cells, which are highly specialized for supplying oxygen to tissues and organs in the body. Produced in the bone marrow, these cells mature into little more than shipping containers for a large, multi-part protein called hemoglobin.
Within hemoglobin, iron molecules are ideally positioned to grasp oxygen molecules and transport them throughout the body. Iron-bound hemoglobin complexes give red blood cells their signature color and are essential to their maturation and function.
DURING THE PRODUCTION OF RED BLOOD CELLS, FUNCTIONAL HEMOGLOBIN IS PRODUCED IN THE BONE MARROW AND PLACED INTO RED BLOOD CELLS, GIVING THEM THEIR SIGNATURE COLOR.
But in patients with beta-thalassemia, mutations disrupt the production of working hemoglobin in the quantities needed, so red blood cells do not mature properly; instead, they are like pale and abnormal small bags. Most importantly, they can’t pick up enough oxygen from the lungs and drop it off throughout the body.
IN PATIENTS WITH BETA-THALASSEMIA, MUTATIONS DISRUPT THE PRODUCTION OF WORKING HEMOGLOBIN, LEADING TO AN OVERPRODUCTION OF ABNORMAL RED BLOOD CELLS THAT ARE PINK-HUED AND UNABLE TO TRANSPORT OXYGEN EFFECTIVELY.
“This inability to make sufficient hemoglobin contributes to chronic anemia,” Piga said. “But another distinctive and aggravating aspect of the disease is that the bone marrow works up to 30 times above, even ineffectively, with a lot of negative consequences including bone deformities.”
Piga is exploring whether it’s possible to disrupt the signals that send the bone marrow into overdrive. The hope is to treat anemia by boosting the number of red blood cells that have sufficient hemoglobin. While Piga admits the strategy would not cure beta thalassemia, it could improve quality of life for many patients living with this inherited blood disorder.
We’re hopeful that we can reduce the need for costly, time-consuming transfusions for patients.
Currently, most patients with severe forms of the disease need regular blood transfusions to shut down the bone marrow’s production of ineffective cells and augment the supply of normal red blood cells. Transfusions are cumbersome, costly and associated with risks, and they can cause complications through all the extra iron from the transfused blood cells. Since the body has no natural way to expel this metal, which can be dangerous at high levels, patients must be treated with chelation therapy to remove the excess iron.
While work remains to be done to understand how to curb the overproduction of ineffective red blood cells and the potential in alleviating chronic anemia, Piga remains optimistic.
“We’re hopeful that we can soon reduce the need for costly transfusions for patients as we continue to search for a cure,” Piga said. “That’s the best message that I can give to the beta-thalassemia community on this year’s International Thalassemia Day.”
To learn more about why new treatments are needed to reduce the need for transfusions in anemia, read “Beta-Thalassemia: Current Treatments Not Enough.”