Gene therapy represents a groundbreaking medical technique that seeks to treat or potentially cure diseases by modifying a person’s genetic material. This approach involves introducing new genetic material into a patient’s cells to compensate for faulty genes, produce a beneficial protein, or target diseased cells. Several such therapies have now received FDA approval. These approved treatments mark a significant advancement in medicine, moving beyond symptom management to address the underlying genetic causes of various conditions.
Therapies for Inherited Genetic Disorders
Gene therapies offer new possibilities for individuals living with inherited conditions caused by a single faulty gene. These treatments aim to correct or compensate for the genetic defect, providing long-term benefits. Different approaches are employed, such as gene editing or the introduction of functional gene copies, depending on the specific disorder.
For inherited blood disorders like sickle cell disease and beta-thalassemia, significant progress has been made. Casgevy (exa-cel) is an approved therapy for severe sickle cell disease, utilizing a CRISPR-based gene-editing approach. This method involves modifying a patient’s hematopoietic stem cells to enable the production of a functional form of hemoglobin, reducing the painful and debilitating effects of the disease.
Lyfgenia (lovo-cel) is another approved treatment for severe sickle cell disease, which uses a lentiviral vector to deliver a functional copy of the beta-globin gene into the patient’s own blood stem cells. Zynteglo (beti-cel) is approved for adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions, also using a lentiviral vector to add a functional beta-globin gene.
Gene therapy has also impacted inherited blindness. Luxturna (voretigene neparvovec-rzyl) is a therapy approved for a rare form of inherited retinal dystrophy, specifically those caused by mutations in the RPE65 gene. This treatment delivers a correct copy of the RPE65 gene directly into the retinal cells through a subretinal injection. The newly introduced gene then enables the retinal cells to produce the protein necessary for normal visual function, potentially improving sight for affected individuals.
Gene therapies also extend to other inherited metabolic and immune disorders. Skysona (eli-cel) is approved for early, active cerebral adrenoleukodystrophy (CALD) in boys. This therapy involves modifying a patient’s hematopoietic stem cells with a lentiviral vector to add a functional copy of the ABCD1 gene, which is mutated in CALD. The modified cells then produce the ALD protein, helping to break down very long-chain fatty acids that otherwise accumulate and cause neurological damage.
Cell-Based Gene Therapies for Cancers
Beyond inherited genetic disorders, gene therapy has found a distinct application in the treatment of certain cancers, particularly through cell-based approaches. These therapies typically involve modifying a patient’s own immune cells outside the body before reinfusing them. This process arms the patient’s immune system to specifically recognize and attack cancer cells.
Chimeric Antigen Receptor (CAR) T-cell therapy is a primary example of this approach. In CAR-T therapy, a patient’s T-cells, a type of immune cell, are extracted from their blood. These cells are then genetically engineered in a laboratory to produce specialized receptors called chimeric antigen receptors (CARs) on their surface. These CARs are designed to specifically bind to proteins found on the surface of cancer cells, enabling the modified T-cells to identify and destroy the malignant cells. After engineering, the CAR-T cells are multiplied and infused back into the patient.
Several CAR-T cell therapies have received FDA approval for various blood cancers. Kymriah (tisagenlecleucel) was one of the first approved CAR-T therapies, used for certain types of B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Yescarta (axicabtagene ciloleucel) is another approved therapy for specific types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma. Abecma (idecabtagene vicleucel) has been approved for relapsed or refractory multiple myeloma, a type of bone marrow cancer.
Addressing Neuromuscular Conditions
Gene therapy has also emerged as a promising avenue for treating severe neuromuscular conditions, which often involve progressive muscle weakness and loss of function. These therapies aim to deliver functional genetic material to the affected cells, often motor neurons, to restore or improve protein production.
Zolgensma (onasemnogene abeparvovec-xioi) is approved for spinal muscular atrophy (SMA) in pediatric patients. SMA is a devastating genetic disorder caused by a mutation in the SMN1 gene, which leads to a deficiency of the survival motor neuron (SMN) protein necessary for the health and function of motor neurons. Without sufficient SMN protein, motor neurons degenerate, resulting in severe muscle weakness, atrophy, and often difficulty breathing and swallowing.
Zolgensma addresses this by using an adeno-associated virus serotype 9 (AAV9) vector to deliver a functional copy of the SMN1 gene. This AAV9 vector is particularly effective because it can cross the blood-brain barrier, allowing the gene to reach motor neuron cells throughout the body after a single intravenous infusion. The introduced gene then enables the cells to produce the missing SMN protein, potentially halting or reversing the progression of the disease.
Elevidys (delandistrogene moxeparvovec-rokl) is approved for Duchenne muscular dystrophy (DMD) in certain pediatric patients. DMD is caused by mutations in the DMD gene, leading to the absence or dysfunction of dystrophin, a protein crucial for muscle integrity. Elevidys uses an AAV vector to deliver a gene that codes for a shortened, functional version of the dystrophin protein, called micro-dystrophin. The goal is to help muscle cells produce this protein, which can potentially improve muscle function and slow disease progression.
The Patient Journey and Administration
Undergoing gene therapy involves a structured process, beginning with a thorough evaluation to determine patient suitability. Medical teams conduct extensive testing to confirm the specific genetic diagnosis and assess the patient’s overall health status. This assessment ensures the patient is an appropriate candidate, considering age, disease progression, and any pre-existing conditions.
Once eligibility is confirmed, the treatment process varies depending on the specific therapy. Some gene therapies, such as Zolgensma for SMA, are administered as a one-time intravenous infusion, delivering the genetic material directly into the bloodstream. Other therapies, like Luxturna for inherited blindness, involve a direct, localized injection into the affected tissue, in this case, the retina of the eye.
For cell-based therapies like CAR-T treatments for cancer, the process is more complex. It begins with leukapheresis, collecting a patient’s T-cells from their blood. These cells are sent to a specialized facility for genetic engineering, modified to target cancer cells. Before re-infusion, patients undergo a short course of conditioning chemotherapy to prepare their body. After re-infusion, patients are closely monitored in a specialized hospital setting.
Long-term follow-up care is a standard component of the patient journey. This monitoring involves regular medical appointments and tests to assess the therapy’s effectiveness and to manage any potential side effects that may arise. The duration and intensity of post-treatment monitoring can vary, but it is designed to ensure the ongoing safety and benefit for the patient.