New research led by the University of Bristol has found that older women may be more sensitive to harmful side effects from gene therapy used to treat incurable eye diseases.
The study, published in the journal Molecular Therapy, shows that both age and gender can influence how the body reacts to these treatments.
In some cases, the immune system’s reaction may actually damage the eye instead of helping it.
These findings could help make gene therapy safer and more effective by encouraging doctors to consider a patient’s age and gender before treatment.
Gene therapy offers new hope for people with vision problems that were once considered untreatable. In the U.K., about 2 million people live with sight loss, and more than 1 million suffer from conditions like age-related macular degeneration, glaucoma, or diabetic eye disease. These illnesses can lead to partial or complete blindness, and many have no cure.
To treat these diseases, gene therapy uses a harmless virus called Adeno-Associated Virus (AAV) to carry healthy genes to the back of the eye. These genes help cells function better and prevent further damage.
However, during clinical trials, doctors noticed that some patients developed eye inflammation after treatment. In rare cases, this caused patients’ vision to worsen.
This inflammation seems to be caused by the body’s immune system mistakenly attacking the virus used in the therapy. When the immune system reacts this way, it can damage eye tissue or make it harder for doctors to adjust the treatment dose.
To better understand this problem, researchers at Bristol tested how eye cells from male and female animals responded to gene therapy. They studied cells from young, middle-aged, and older animals, focusing on how the immune system reacted to the treatment.
In younger animals, male and female eye cells responded similarly at first, but researchers noticed some deeper differences in how the cells acted at the molecular level.
As the cells aged, their immune responses lasted longer and became stronger in both sexes. However, older female cells had the most intense inflammation and showed signs of stress and damage in the retina.
In contrast, older male cells responded in a more stable way, suggesting that older women may face a higher risk of side effects from gene therapy.
Dr. Alison Clare, the lead researcher, said these findings are the first to show that both age and sex can impact how safe gene therapy is for the eyes. She explained that this could help doctors better understand which patients are more likely to have serious reactions and how to prevent them.
The study highlights the need for personalized treatment plans that take into account each patient’s age and gender. Doing so could make gene therapy safer and more successful for more people, especially older women who may be more vulnerable.
Looking ahead, scientists hope to improve gene therapy by finding ways to control the immune response. This could lead to safer treatments for many people suffering from vision loss.
As this research moves forward, it brings us closer to a future where gene therapy is tailored to each patient, helping to restore vision without causing harm.
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