The future of Sickle Cell Anemia

 With continuous modernization of medicine, we are able to address diseases and disorders that would not have been possible previously. Somewhat recently the FDA announced the approval of two of the first cell-based gene therapies for sickle cell anemia (SCA), Casgevy and Lyfgenia. 

Casgevy uses CRISPR/Cas9 to modify the patient's own blood cells, specifically their hematopoietic stem cells. It specifically modifies the hematopoietic stem cells to increase the production of fetal hemoglobin (HbF), which address the issue of the Glu6Val mutation on the Beta chain in their original blood cells. The change from HbA to HbF prevents the aggregation of blood cells and prevents the sickling shape of the red blood cells.   

Lyfgenia is a cell-based gene therapy. It uses a vector for gene delivery to create the genetic modification. The modification of this treatment results in a HbA^T87Q, a Hb variate that functions very similarly to HbA which has a lower chance of sickling and blood cell aggregation/occlusion. 

Both treatments target the patient's hematopoietic stem cells, so patients must undergo a high-dose chemotherapy treatment to kill all their original mutated stem cells that were producing the sickled cells. Once the original bone marrow has been removed, now it can be replaced with the genetically modified hematopoietic stem cells, which will begin producing the modified versions of either HbF (Casgevy) or HbA^T87Q (Lyfgenia). 

The Casgevy study's primary outcome goal was for patients to not experience a severe vaso-occlusive crises (VOC) for a consecutive 12 months during the 24 mo follow-up period. 44 patients were treated with Casgevy, and 31 had sufficient follow up, 29 of the 31 patients (93.5%) experienced at least 12 consecutive months VOC free. Even better was that none of the patients experienced graft failure or rejection and successfully engrafted the gene edited cells. 

Lyfgenia focused on addressing voso-occlusive events (VOE) rather than crises with a criterion of complete resolution of VOE between 6 and 18 months after the treatment of Lyfgenia. 28 of 32 patients (88%) achieved resolution. However, it should be noted that blood cancer did occur in patients, future patients who are treated with Lyfgenia should have lifelong monitoring for possible malignancy. 

In summary, the treatment of SCA has a bright future, especially as the scientific community continues to see innovative advancements of gene therapy. 

(FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease | FDA, n.d.)

https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease