Summary of New Hope for Treatment of Rare Metabolic Brain Disease:
This article discusses a clinical trial for a new drug to treat X-linked adrenoleukodystrophy (X-ALD), a rare genetic disorder that affects the nervous system and adrenal glands. The study found that the drug leriglitazone was successful in preventing life-threatening inflammation of the brain and had a positive impact on neurological conditions such as balance disorders. The European Medicines Agency is currently reviewing the marketing authorization application of the drug, sponsored by the Spanish pharmaceutical company Minoryx.
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New Drug Could Help Treat X-Linked Adrenoleukodystrophy
X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder that affects the nervous system and adrenal glands. It is caused by a mutation in the ABCD1 gene on the X chromosome and is characterized by progressive damage to the myelin sheath surrounding the nerve fibers in the brain and spinal cord. Symptoms may include behavioral changes, difficulty with coordination and movement, and vision and hearing loss.
Controlled Clinical Trial Reveals Positive Results
Scientists from leukodystrophy centers in Europe and the US have jointly succeeded in obtaining controlled trial data for X-linked adrenoleukodystrophy. Of the 116 patients, 77 received the drug leriglitazone and 39 a placebo. The drug had already shown in preclinical studies that it can prevent neurodegeneration and offer protection against the life-threatening inflammation of the brain.
“Our clinical trial has in fact also shown that none of the patients who took the drug were affected by brain inflammation. In contrast, among the participants who were given a placebo, 15 percent developed this life-threatening form of the disease within two years,” explains study leader and first author Dr. Wolfgang Köhler, head of the leukodystrophy outpatient clinic at the Department of Neurology at Leipzig University Hospital.
The actual aim of the study had been to show that the drug would prevent gait disorders in X-ALD patients from worsening over the course of two years. “This worked particularly well in those who were treated early. The more advanced the gait disorder, the less apparent the effect. Overall, there was no significant difference, so the actual aim of the study was not achieved,” explains Dr Köhler. Nevertheless, many points indicated a clinical effect of the new drug: besides the indication that brain inflammation could be prevented, other effects included improvements in neurological conditions such as balance disorders, which had a positive impact on quality of life.
More Information on the Study
All participants in the study currently have the option to continue treatment with leriglitazone for a total of five years as part of an open-label extension study. In addition, follow-up studies are planned in patients with pre-existing involvement of the brain. “This gives us hope that we will also be able to effectively treat patients with advanced, inflammatory brain involvement with a drug in the future, especially those whom we can no longer help with a stem cell transplant. This is only possible at a very early stage of brain inflammation,” explains Dr. Köhler.
A center for myelin disorders, which include leukodystrophy and multiple sclerosis, is to be established at Leipzig University Hospital before the end of this year, and will be the first of its kind in Germany. “With such rare diseases, it is of utmost importance to bring together the excellence of different areas of treatment and research in order to jointly gain new insights and make further progress,” says initiator Dr. Köhler.
Next Steps for the Drug
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) is currently reviewing the marketing authorization application of the Spanish pharmaceutical company Minoryx for the drug leriglitazone for the treatment of adult male patients with X-ALD. This study was sponsored by Minoryx.
The results of this clinical trial offer hope to those who suffer from X-ALD, as it has shown that leriglitazone could potentially prevent brain inflammation and improve neurological conditions. With further research and the establishment of a center for myelin disorders, scientists may be able to find a more effective way to treat this rare disorder.
