This technology involves a pharmaceutical composition for the prevention and treatment of X-linked adrenoleukodystrophy (X-ALD) and a health food product for prevention and improvement, containing 25-hydroxycholesterol or its derivatives with an acetyl group at the R1 position as an active ingredient. It targets various subtypes, including childhood cerebral ALD (CCALD), adult adrenomyeloneuropathy (AMN), and cerebral adrenomyeloneuropathy (cAMN).
X-ALD is a congenital metabolic disorder caused by ABCD1 gene mutations, where saturated very long-chain fatty acids (VLCFAs) like C26:0 cannot be broken down and accumulate, leading to myelopathy and cerebral demyelination. However, there have been no clinical treatments to halt its progression. Lovastatin failed to significantly lower blood VLCFA levels in clinical trials, and Lorenzo's oil, used as a dietary supplement, also has limitations in preventing disease progression.
This technology utilizes the ability of 25-hydroxycholesterol to lower intracellular very long-chain fatty acid levels. It uses an active ingredient that has been confirmed to reduce C26:0 in patient-derived CCALD/AMN cells and oligodendrocytes differentiated from induced pluripotent stem cells. It has a clear mechanism of action by directly regulating the accumulation of the causative metabolite. Applicable to treatments for childhood cerebral ALD, inhibitors for adult AMN progression, and dietary management health foods for rare metabolic diseases, it offers a new therapeutic approach targeting the accumulation of very long-chain fatty acids in X-ALD, a condition with few treatment options.
This invention was developed with support from the Ministry of Education for research on discovering regulatory substances for novel therapeutic targets in KRAS-mutant lung cancer.
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