Current Treatment Research
Scientists are still searching for comprehensive treatments for ALD and AMN. For the ALD cerebral onset, an approach is needed that would overcome some of the limitations and risks of stem cell transplantation and offer a wider therapeutic window than current transplantation or Lorenzo’s oil. For AMN, the adult version of ALD, options are needed to help with symptoms and prevent further deterioration.
One of the most promising treatments on the horizon for ALD is gene therapy. This involves inserting the corrected genetic sequence with the appropriate ‘blueprints’ into cells. The repaired cells will then produce the ALD protein that had been missing or defective prior to treatment, and the disease process will halt or moderately reverse.
Since stem cell transplants (using donor bone marrow or umbilical cord blood) has been shown to halt the disease process, the idea behind gene therapy is to use a patient’s own stem cells rather than those of a donor. This involves temporarily removing the stem cells from the person with ALD, inserting the corrected genetic sequence into these cells, and putting them back into the patient.
If a patient uses their own corrected stem cells, rather than a donor’s stem cells, it is called an ‘autologous transplantation’. In an autologous transplantation cells are removed from an individual and reimplanted in that same individual. Because each person is their own donor, all of the problems and risks that arise from using an outside donor for stem cells can be obviated or significantly lessened.
Successful gene therapy would yield the same positive results of stem cell transplantation, for many more patients, with far fewer risks.
Early trials are very preliminary, but they appear very promising so far. Four boys with ALD have been treated with gene therapy in France; the first received his transplant in September 2006, and the second in early 2007. The results of the first two boys were published in Science November 2009.
While gene therapy may be of great therapeutic value prior to the onset or at the early stages of ALD symptoms, it will not address the needs of boys who are only diagnosed after significant disease progression.
Advantages of Autologous Transplants
Other new treatment options, that may provide hope even after the disease has begun to ravage the brain, are also being studied. In early 2007, scientists from the University of Minnesota reported that treatment with a drug called Mucomyst (acetylcysteine), appears to provide protection from rapid neurological decline in the advanced form of ALD. (Bone Marrow Transplantation (2007) 39, 211–215. doi:10.1038/sj.bmt.170557) (Mucomyst is generally used in the treatment of various lung diseases in which mucus makes breathing difficult.) Previously, boys with ALD as advanced as the three boys in this study had all died within a year of stem cell transplantation, but these boys saw their condition stabilize. This may mean that treatment with Mucomyst could allow a larger group of ALD patients, with more advanced brain damage, to successfully receive stem cell transplantation.
Other possibilities now being studied by scientists funded by the Foundation include ALDR upregulation, in which a gene very similar to the ALD gene, which already exists in a normal form in people with ALD, could be ‘upregulated.’ By increasing the activity of the normal gene, we hope to be able to compensate for the deficiencies of the abnormal gene.
Mesenchymal Stem Cell Therapy
Scientists at several institutions are studying the use of mesenchymal stem cells (MSC’s) in treating ALD. These cells are multipotent precursor cells that can differentiate into many different types of cells. Cultured from adults’ bone marrow, they may have promise in treating ALD when delivered directly into the blood, spinal cord, and brains of people with the disease. Clinicians at University of Minnesota plan to initiate a study where boys who were diagnosed fairly late in the disease process would be treated with MSC’s. The intention is to halt the rapid deterioration and potentially allow for a transplant to be effective.
The Myelin Project is pursuing research into therapies that could actually restore the lost myelin, potentially reversing the damage done by the disease. They are funding two avenues of potential remyelinating therapies: transplantation of myelin-forming cells, and drugs that would replace the lost myelin.
Oxidative stress has been shown to play a key role in the deterioration seen in AMN. Several agents are being investigated.
Please find below a list of current clinical trials.
All adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN) clinical trials on Clinicaltrial.gov can be found here.
Bluebird Bio has a gene therapy program for childhood cerebral ALD (CCALD), As of October 2018, Clinicaltrials.gov shows "enrolling by invitation", so if a patient qualifies for a stem cell transplant they may want to reach out to BlueBird.
Minoryx has a trial enrolling patients with adrenomyeloneuropathy (AMN).
Stanford is conducting a vitamin D trial for boys with ALD.
In August 2018 Poxel acquired DRX-065 from DeuteRx. DRX-065 completed a FDA Phase I safety study.
Orpheris has a compound for childhood cerebral ALD (CCALD) which is finished FDA Phase I safety.
NeuroVia had a trial for childhood cerebral ALD (CCALD). As of October 2018 the study is on hold meaning they are not recruiting patients and the study is not currently active.