Until recently, life for most people with sickle cell disease was a constant battle. The years were filled with pain, affecting every aspect of life—school, relationships, and work. But then, a new era dawned: a life after sickle cell disease. This is the story of two Americans whose lives were transformed by the advent of newly approved gene therapies. They share their journey with AFP, hoping others will find solace in these groundbreaking treatments.
A new technology known as CRISPR/Cas9 allows scientists to precisely add, remove, or alter DNA sections. It’s a breakthrough in gene therapy, which uses small nucleic acid sequences to affect how genes are translated into proteins. Those proteins are then used to treat diseases.
For the first time, scientists used a CRISPR/Cas9 system to edit a patient’s blood stem cells to produce a functional form of hemoglobin, a protein in red blood cells that facilitates oxygen delivery. The modified stem cells were then transplanted back into the patient’s bone marrow, where they engrafted and produced healthy red blood cells that are less likely to sickle or obstruct blood flow. The treatment is called LentiGlobin and is now being trialed at Columbia University Irving Medical Center.
The treatment is only available to patients aged 12 and older who have a history of painful, life-threatening vaso-occlusive events (blockages caused by sickle-shaped red blood cells) or a high risk for them. It’s the second gene therapy to be approved in recent months. The other, a drug called Hemlibra, is designed to increase the production of fetal hemoglobin in healthy red blood cells, reducing the risk that they will sickle.
A third gene therapy, in a phase 2 clinical trial at Boston Children’s Hospital, is designed to boost the production of fetal hemoglobin using post-transcriptional gene silencing. This technique works by binding to a messenger RNA that activates a gene and blocks its activity.
These approaches are all promising, but their success hinges on the ability to make them cost-effective and widely accessible. One hurdle is overcoming the immune system’s tendency to reject genetically engineered cells to replace patients’ cells.
NIH researchers have made a significant breakthrough in mice, demonstrating the potential to overcome the immune system’s rejection of genetically engineered cells. By tweaking the genes that regulate how the immune system responds, they have paved the way for a similar approach in human gene therapy. This is a critical step towards making gene therapy more accessible and affordable, instilling confidence in its effectiveness.
The future of medical advancements holds excellent promise. The ultimate goal is to treat complex conditions with multiple genes by combining gene therapy with other treatments. One such strategy is a drug called hydroxyurea, which reduces inflammation in the body and boosts production of fetal hemoglobin. In a small clinical trial, this combination restored vision in patients with Leber congenital amaurosis, a degenerative eye condition. This is just a glimpse of the potential, offering hope for those affected by complex conditions.
