Gene therapy is a promising therapeutic procedure for genetic disorders or diseases in which defective genes are corrected, replaced, or inactivated.

In the case of adrenoleukodystrophy (ALD) — a genetic disorder caused by mutations in the ABCD1 gene that damages the myelin sheath around nerve cells — gene therapy may benefit patients prior to the onset, or during the early stages, of the disease by stopping the progression of demyelination. However, the therapy cannot be beneficial after the disease has worsened significantly.

How gene therapy works

Gene therapy works by introducing the correct gene sequence into cells. Since genetic material cannot enter the cell on its own, the correct gene sequence needs to be delivered using a vector. This vector can be a modified virus that has been engineered to remove its pathogenic genetic material so that it cannot cause disease, but is still able to transfer the correct gene sequence to the host cell.

The vector can be directly injected into the patient’s body or into host cells grown in the laboratory and then transplanted back into the patient. Upon successful viral transfer, the host cell should be able to produce the functional protein.

In ALD, the clinician first takes out the patient’s own stem cells (autologous) and then inserts the correct ABCD1 gene sequence into these cells using a viral vector in the laboratory. The corrected stem cells that are able to produce the functional ALD protein are then implanted back into the patient’s body so they may develop into nerve cells in the brain. Since the patient’s own cells are being used, there are fewer risks than when donor stem cells are used.

Gene therapy in clinical trials for ALD

Lenti-D, an investigational gene therapy developed by Bluebird Bio is currently being studied in a Phase 2/3 clinical trial, called STARBEAM (NCT01896102), and a long-term follow-up study (NCT02698579). Another Phase 3 trial (NCT03852498) is currently recruiting new patients. The studies aim to evaluate the safety and effectiveness of Lenti-D in boys, up to 17 years old who have cerebral adrenoleukodystrophy (CALD). Based on data from the STARBEAM and the long-term follow-up study, Bluebird Bio submitted a marketing authorization application (MAA) with the European Medicines Agency in October 2020.

A Phase 1/2 clinical trial (NCT02559830) is recruiting patients with ALD at the Shenzhen Second People’s Hospital in Guangdong, China. The study aims to assess the safety and effectiveness of transplanting patient-derived bone marrow stem cells, which have been genetically-corrected using a lentiviral vector, for the treatment of ALD.

Another Phase 1/2 clinical trial (NCT03727555) at the Shenzhen Geno-Immune Medical Institute also in Guangdong, China is recruiting 10 patients with ALD. The study aims to evaluate the safety and effectiveness of a lentiviral vector carrying the healthy ABCD1 gene (TYF-ABCD1) injected directly into the patient’s brain for the treatment of ALD.


Last updated: Dec. 24, 2020


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