Development of a Potential Therapeutic for Better Management of Patients with Adrenoleukodystrophy
Adrenoleukodystrophy, also known as ALD, is a rare X-linked disease. It is caused by a mutation in the peroxisomal ABCD1 gene, which encodes a protein that transports very long-chain fatty acid (VLCFA, C26:0) into the peroxisome for β-oxidation. The presence of a defective transporter will lead to an abnormal accumulation of VLCFA, specifically in the adrenal cortex, spinal cord, and brain, thus affecting the nervous system. Currently, there are limited treatments available for ALD. The Kartha lab at the UMN Center for Orphan Drug Research has been actively exploring new safe and effective therapies for individuals with ALD. They have initiated studies to investigate if a dietary supplement, nervonic acid (C24:1) could biochemically prevent progression or delay the onset of the disease by reducing C26:0. Nervonic acid (NA) is known to be safe and available for human use and was proposed to prolong functionality in both children and adults with demyelinating diseases. Given that NA has been found deficient in the brain of ALD patients, it could be given to ALD patients as a dietary therapy to prevent demyelination. Hence, we propose to examine the benefits of NA in a mouse model of ALD. The main goal of my project is to help develop the ideal formulation for animal testing. We will use Captisol®, a chemical designed to increase solubility and stability of lipophilic drugs, for making this formulation. I will dissolve NA in Captisol® and determine the optimal concentration for solubilizing NA in Captisol.