Gene Therapy For Cerebral Adrenoleukodystrophy

What is Gene Therapy?

Gene therapy is a treatment method to prevent disease by inserting a gene into a patient’s cells instead of using conventional drugs or other modern methods. A treatment could be to address a mutated gene or a new gene with health benefits.

What is Cerebral Adrenoleukodystrophy?

Adrenoleukodystrophy (ALD) is a genetic disorder which causes damage to the myelin sheath of the brain. ALD is caused by mutations in ABCD1, a gene located on the X chromosome. Mutations in ABCD1 result in abnormal breakdown of fatty acids. Most patients with cerebral ALD die within a decade after diagnosis if not treated. There are different methods to treat various levels of ALD such as dietrary therapy by restricting the intake of harmful fatty acids, or transplant using alllogeneic hematopoietic stem cells.

What is the latest progress?

A group of doctors and researchers recently used gene therapy (Lenti-D) to improve health conditions for 15 out of 17 patients/boys with ALD disorder. To become eligible for the latest treatment, a score on the cerebral ALD (0 to 25, with high scores indicating more severe deficits) and a Loes scores (0 to 34, with high scores indicating an increased extent of lesions on MRI) must be met. CD34+ cells from each patient was transduced with the Lenti-D lentiviral vector to make the drug product. The Lenti-D drug product contained 6 to 19.4 million CD34+ cells per kilogram of body weight. To expedite engraftment (blood-forming cells on transplant to grow and make healthy blood cells),  granulocyte colony-stimulating factor (G-CSF) was used after the infusion. Expression of ALD protein was observed. The percentage of CD14+ cells that expressed ALD protein varied about 65% at 6 months after infusion among all patients and 34% at 24 months. Plasma levels of fatty acids were unaffected by treatment with Lenti-D.

Preliminary results suggest that Lenti-D gene therapy seems safe and stable for the patients in this study. Although patients with low scores (<1 cerebral ALD score and <9 Loes score) could benefit from this treatment, it remains unknown for those with more severe symptoms of ALD. Nonetheless, this study is a positive progress to halt progression of the ALD disease and to encourage more resources for gene therapy that could potentially treat or prevent other diseases.

Eichler et al., Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy, The New England Journal of Medicine, 2017, 377(17).

On December 19th, 2017, U.S. Food & Drug Administration (FDA) approves the gene therapy method as described above to treat patients with a rare form of inherited vision loss. The approved drug is called Luxturna (voretigene neparvovec-rzyl). Luxturna is made by Spark Pharmaceuticals. Although the cost for using the drug has not yet determined by the company, the speculation seems to indicate that it would cost roughly $1,000,000.00 to treat each patient.



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