Gene Therapy Shows Potential to Mitigate Stroke Risk in Sickle Cell Patients

A recent study conducted by St. Jude Children’s Research Hospital has unveiled promising results regarding the use of gene therapy in patients with sickle cell disease, particularly concerning the management of stroke risk. The research, published in the *American Journal of Hematology* on June 30, 2025, indicates that gene therapy may significantly improve cerebral blood flow in individuals predisposed to strokes due to their condition.

Sickle cell disease is characterized by the abnormal shape of red blood cells, which can obstruct small blood vessels, including those in the brain. This obstruction can lead to ischemia, a condition where the brain is deprived of adequate oxygen, increasing stroke risk. According to Dr. Akshay Sharma, MBBS, MSc, corresponding author and a member of the St. Jude Department of Bone Marrow Transplantation & Cellular Therapy, the study observed a normalization of elevated blood flow speeds in three patients after undergoing gene therapy, thereby suggesting a mechanistic pathway for reducing stroke risk in this vulnerable population.

Dr. Sharma stated, “We saw that after gene therapy, elevated blood flow speed in the brain came down to normal levels. This is the closest physiological evidence we have that gene therapy could be effective for patients with neurovascular disease who are at risk of or have had a stroke.” This finding is particularly significant given that traditional treatments, such as hydroxyurea and blood transfusions, offer limited, transient benefits in improving brain blood flow.

The clinical trial involved imaging the patients’ brains using Magnetic Resonance Imaging (MRI) both prior to and two years post-treatment. Results indicated a substantial reduction in blood flow speed, between 22% to 43%, with improvements remaining stable over time. This suggests that gene therapy may provide a more durable solution compared to current standard therapies.

Historically, patients with sickle cell disease who are at risk for strokes have been excluded from gene therapy trials due to the high-risk nature of their condition. However, this study advocates for the inclusion of such patients in future clinical trials. The authors, which include researchers from the University of Chicago Medicine and Novartis Institutes for Biomedical Research, emphasize the need for further investigation to confirm these preliminary findings and to explore the long-term efficacy of gene therapy in protecting brain health.

The results of this study contribute to a growing body of evidence that gene therapy could serve as a viable alternative for patients with sickle cell disease, particularly those at risk for neurovascular complications. As stated by Dr. Sharma, “Until now, we only had one option that had a long-term impact on blood flow in the brain: bone marrow transplantation. But now we may also have gene therapy as another viable method to protect against neurovascular disease in people with sickle cell disease.”

The study's funding was supported by Novartis Pharmaceuticals Corporation, USA, highlighting the potential for future research and development in this area. As gene therapy continues to evolve, its implications for treatment strategies in sickle cell disease and associated risks of stroke warrant close attention from the medical community and stakeholders in public health.