Gene Therapy for Adrenoleukodystrophy (ALD)

Adrenoleukodystrophy (ALD) is a genetic disease that most severely affects boys. Caused by a defective gene on the X chromosome, it triggers a build-up of fatty acids that damage the protective myelin sheaths of the brain’s neurons, leading to cognitive and motor impairment. The most devastating form of the disease is cerebral adrenoleukodystrophy (CALD), marked by loss of myelin and brain inflammation. Without treatment, ALD ultimately leads to a vegetative state, typically claiming boys’ lives within 10 years of diagnosis. 

How ALD gene therapy works

ALD is caused by a mutation to the ABCD1 gene on the X chromosome. ABCD1 controls the body’s production of an enzyme known as ALD protein, which normally breaks down fatty acids; however, when a mutation interrupts the function of ALD protein, fatty acids build up and accumulate causing widespread demyelination, often accompanied by adrenal gland dysfunction.

Newborn screening and childhood genetic testing can identify the defective ABCD1 gene before symptoms of adrenoleukodystrophy occur, creating a small window of opportunity to prevent the disease’s degenerative effects before they begin to irreversibly accumulate.

To perform the gene therapy, a patient’s blood stem cells (these are the cells that give rise to all mature blood stem cells) are collected. In a highly-specialized laboratory, a viral vector is used as a carrier to insert a correct version of the faulty ABCD1 gene into the patient’s stem cells. Then, the patient receives chemotherapy to make room for the genetically-altered cells. Finally, the cells are given back to the patient via an intravenous infusion.

Illustration of SCID-X1 gene therapy


ALD gene therapy clinical trial

Clinical Study to Assess the Efficacy and Safety of Gene Therapy for the Treatment of Cerebral Adrenoleukodystrophy (CALD)
Recruiting males up to 17 years old (full eligibility criteria)
Boston Children's Hospital

Started: Jan. 2019

Christine Duncan, principal investigator
Colleen Dansereau, MSN, RN, CPN617-919-7008 or colleen.dansereau@childrens.harvard.edu

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