Stem cell therapy is a treatment that has been proven effective in arresting disease progression in some cases of adrenoleukodystrophy (ALD).

What is ALD?

ALD is a serious genetic disorder characterized by the loss of the protective protein coat that surrounds nerve fibers. Without this protective coat, the nerve cells are fragile and easily damaged, which leads to neurodegeneration. ALD also affects the secretion of hormones from the adrenal glands, which can have serious consequences for growth and development, as well as many other aspects of life.

ALD is caused by a mutation in a gene called ABCD1, which encodes for a protein involved in the breakdown of a particular kind of fat called very long-chain fatty acids (VLCFAs). Without this protein, VLCFAs accumulate in the nervous system and blood, causing damage.

What is stem cell therapy?

Stem-cell therapy uses stem cells to treat or prevent a disease or condition. The type used to treat ALD is called hematopoietic cell transplantation, which is a transfusion of stem cells that can become blood cells. The transfused cells secrete enzymes, which can help the patient’s own cells process the excess VLCFAs. Stem cell therapy can halt the progression of the disease but cannot reverse the neurological damage already done. Therefore, the treatment must be started as soon as possible after diagnosis.

The transfused cells could be bone marrow or umbilical stem cells, and come from a stem cell donor. The patient’s immune system must, therefore, be suppressed with radiation or chemotherapy before infusing the donor cells so it does not attack and destroy these cells. This immune suppression makes patients very susceptible to infection. Even a well-matched donor sample may fail to “take,” and the disease may progress during the first few months after the transplant. These factors make stem cell therapy very high-risk.

Another experimental stem cell transplant therapy involves isolating stem cells from the patient, and correcting the mutation with gene therapy before transfusing the cells back into the patient’s body. Because this procedure involves the patient’s own cells, the immune system should not recognize them as foreign, so there should be no need for radiation or chemotherapy before treatment. This type of transplant is called autologous, to indicate that the patient’s own cells are being transplanted.

Stem cell therapy in clinical trials for ALD

A clinical trial (NCT02204904) currently recruiting young males in the U.S. and Europe is evaluating the safety and efficacy of allogenic hematopoietic stem cell transplantation. The trial aims to recruit 60 male participants, younger than 18 years old. The patients will be divided based on when they were recruited to the study (pre- or post-transplant). The study also plans to include retrospective data from patients who received a transplant and had died prior to the beginning of the study. The primary outcome measured will be transplant-related mortality (not mortality due to disease progression). The study is expected to conclude in 2021.

An ongoing Phase 2/3 clinical trial (NCT01896102) is assessing the efficacy and safety of hematopoietic stem cell transplants following a gene therapy that will alter the genome of the transplant cells so that they express the protein that is missing in ALD. The study is open label and expected to recruit 30 male participants younger than 18. The primary outcome measure will be disability present at 24 months following transplant.

A Phase 1/2 clinical trial (NCT02559830) is currently recruiting ALD patients in China to evaluate the safety and efficacy of autologous hematopoietic stem cell therapy for advanced stage ALD and a similar disease called metachromatic leukodystrophy. A total of 50 patients are expected to receive genetically modified stem cells. Safety and efficacy will be established immediately, following transplant, and at later time points.


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