Cerebral adrenoleukodystrophy (CALD) is a rare progressive genetic brain disease that occurs primarily in young boys, causing loss of neurological function and ultimately leading to premature death. The disease is caused by mutations that induce very long chain fatty acids to accumulate in the blood, brain, nervous system and adrenal glands.
The study is a clinical trial conducted in 32 patients with cerebral adrenoleukodystrophy who received the first gene therapy approved (by the US FDA in 2022) for CALD, elivaldogene autotemcel (eli-cel).
Gene therapy uses a lentiviral vector Lenti-D to deliver a healthy copy of the ABCD1 gene—the defective gene in people with CALD—to blood stem cells that have been taken from the patient. These stem cells are then reintroduced into the patient via an autologous hematopoietic stem cell transplant. Using the patient’s own cells can significantly reduce the risk of graft-versus-host disease.
The analysis reveals that:
- 6 years later, 94% of participants did not show a decline in their neurological functioning;
- more than 80% do not suffer from a major disability;
- Taken together, these initial results suggest gene therapy as the first viable and promising option for this group of patients.
One of the lead authors, Dr. Florian Eichler, director of the leukodystrophy clinic in the Department of Neurology at Massachusetts General Hospital, tells “When I began treating patients with CALD, this devastating brain disease that strikes children in the prime of life and development, 80% of them arrived “at death’s door.”
Today, the ratio has reversed.
We are cautiously pleased to be able, in many cases, to stabilize this neurological disease and return these boys to a fulfilling life, with one caveat, however: we observe malignancy in a subset of these patients.”
Researchers are continuing research into the possible causes of this hematological malignancy and are working in particular to improve lentiviral vectors. Neonatal screening for adrenoleukodystrophy is also underway, and could improve the capacity for early detection of the disease, with an increased possibility of patients who can benefit from gene therapy.
