Adrenoleukodystrophy (ALD)
https://pubmed.ncbi.nlm.nih.gov/35510808/
This article reviews the efficacy of a new drug called PXL065 used to treat X-linked Adrenoleukodystrophy (ALD). This condition is a rare neurometabolic (affecting the metabolism in neurons) disorder caused by mutations in the ABCD1 gene which encodes for a transport protein. The protein is responsible for transporting very-long-chain fatty acids (VLCFA) across the cell membrane to the peroxisomes (organelles of the cell used to metabolize substances). When the protein is impaired the VLCFA is not transported to the peroxisomes leading to their accumulation in tissues and plasma. This results in two subtypes of the condition, the Adrenomyeloneuropathy (AMN) and the cerebral- ALD (C-ALD). The first one is diagnosed during adulthood and is characterized by spinal cord and nerve degeneration (loss of neurons or their function). On the other hand, C-ALD is diagnosed during childhood with neurological impairments being the primary cause of loss of life due to the deterioration of white matter in the brain. There is an available treatment for the condition but there are associated side effects. For that reason, scientists repurposed a drug – originally used to treat diabetes- called PXL065 which can be used to treat both subtypes of the disease. Throughout research conducted to evaluate the efficacy of the drug, chronic administration revealed reductions of VLFCA in plasma and tissue of mice. Moreover, it is able to repress inflammatory responses which could lead to ALD. The drug is currently assessed for both its success and safety, enabling it a potential treatment for the condition with minimal side effects for the patients.