Compound for the Treatment of Canavan Disease


Project ID: D2016-26



Defects in the metabolism of N-acetyl-L-aspartate (NAA) have been shown to be the underlying cause of Canavan disease (CD). Canavan disease is a fatal neurological disorder with no known current effective treatment. It is caused by mutations in the gene that encodes the enzyme aspartoacylase (acy2), which is responsible for the deacetylation of NAA in the brain. As a consequence, NAA accumulates to high levels in patients with CD. Multiple mutations in the acy2 gene lead to mutant enzyme forms with inadequate catalytic potential to produce sufficient levels of acetate or to lower the accumulation of NAA. For many years, the prevailing opinion had linked acetate deficiency to the brain developmental disorders that are apparent in CD patients. However, it has been shown that a knockout of the Nat8l gene that encodes aspartate N-acetyltransferase (ANAT), the enzyme that catalyzes NAA synthesis, leads to a reversal of the CNS demyelination in animal model of CD, but also appears to cause increased survival risks. It would therefore be advantageous to develop ANAT inhibitors to treat symptoms of CD without introducing increased risks.


Invention Description

Researchers at the University of Toledo, led by Dr. Ron Viola, have developed fusion enzymes to obtain, for the first time, an active, stable and soluble form of aspartate N-acetyltransferase (ANAT). The team has also developed and optimized compound libraries that slow the production of NAA by inhibiting ANAT for the treatment of CD.



•       The enzyme forms developed may be used in develop screening methods for ANAT inhibitors and to developed treatment for CD

•       The fusion enzymes may be included as part of a kit for CD-related research

•       The compounds developed may be used for the treatment of CD

•       The compounds may also be tested and developed against advanced stage lung and ovarian cancer


•       The identified ANAT inhibitor compounds may be easily synthesized and optimized

•       The fusion enzyme exhibits high solubility and increased stability of the ANAT enzyme in detergent

•       The compounds may be easily administered to patients via a variety of modes

•       Several compounds have been systemically optimized to produce sub-micromolar inhibition of the ANAT enzyme


IP Status:       Patent pending, US 20180340156A1



       Wang Q et al., Purification and characterization of aspartate N-acetyltransferase: A critical enzyme in brain metabolism. Protein Expression & Purification, 2016, 11-18


       Thangavelu B et al., Design and optimization of aspartate N-acetyltransferase inhibitors for the potential treatment of Canavan disease.        Bioorganic & Medicinal Chemistry, 2017, 870-885


Patent Information:
For Information, Contact:
Lokesh Mohan
Licensing Associate
The University of Toledo
Ronald Viola
Qinzhe Wang
Mojun Zhao
Gwenn Parungao