Method to Develop Compounds for Treating Canavan Disease
Project ID: D2016-26IP Status: PCT patent application filed Invention Description and Novelty: Canavan disease is a neurological disease caused by an interruption in the metabolism of N-acetylaspartate (NAA). Numerous mutations have been found in the enzyme that hydrolyzes NAA, and the catalytic activity of aspartoacylase is significantly impaired in CD patients. It is believed that the enzyme that catalyzes the synthesis of NAA in the brain plays an important role in CD. However, prior attempts to express and purify this enzyme have not succeeded in obtaining a soluble, stable, and active form of this membrane-associated protein. Researchers at The University of Toledo have created fusion proteins to obtain an active, stable and soluble form of aspartate N-acetyltransferase (ANAT). Applications: Methods for developing enzymes to be used to treat Canavan Disease. Value Propositions:• Methods of screening for ANAT inhibitors, and developing treatments for Canavan disease.• Successful extraction from membranes and purification of the ANAT enzyme has been accomplished and confirmed by independent sources.• Fusion protein exhibits higher solubility and increased stability of the ANAT enzyme in various detergents.• Provides variants of the fusion proteins including an ANAT variant having up to 99% sequence identity to the amino acid sequence of human ANAT• Provides variants of the solubilizing partner up to 99% sequence identity to the solubilizing partner.• Fusion proteins and methods described herein can be embodied as parts of a kit or kits.
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