Potent Compounds for the Treatment of Canavan Disease & Cancers


Project ID: D2016-55


Invention Description:

Elevated levels of N-acetylaspartate (NAA) is a major hallmark of Canavan disease (CD), which currently has no cure or standard course of treatment. Mutations in the aspA gene, which encodes aspartoacylase, render it unable to adequately catalyze the synthesis of NAA in CD patients. The Nat8l gene encodes aspartate N-acetyltransferase (ANAT), the enzyme that catalyzes NAA synthesis. Knockout of Nat8l has been shown to reverse the effects of CD. However, the Nat8l knockout also drastically reduces survival in CD animal models. In addition to CD, elevated levels of NAA and overexpression of ANAT have been found to correlate with advanced stage lung cancer and ovarian cancer. Researchers at the University of Toledo have developed methods and optimized two compound libraries that slow the production of NAA by inhibiting ANAT. The MBP-ANAT fusion construct is stable, soluble, and highly active, and is suitable for scaled-up production and high-throughput screening studies.



•       The compounds may be used for the treatment of Canavan disease.

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



•       The method generates a host of compounds that may be optimized for ANAT inhibition.

•       Identified compounds may be easily synthesized and optimized through a variety of methods.

•       Compounds may be safely administered to subjects via a variety of modes.

•       Several of the compounds were systematically optimized to produce sub-micromolar inhibition of the ANAT enzyme. This method will allow easy synthesis and potent inhibition of the enzyme.


IP Status:        Patent pending, WO2017172476 A1


Publications:        1. Viola RE et al. Design and optimization of aspartate N-acetyltransferase inhibitors for the potential treatment of Canavan disease. Bioorg Med Chem. 2017 Feb 1;25(3):870-885

2. Viola RE et al. Purification and characterization of aspartate N-acetyltransferase: A critical enzyme in brain metabolism. Protein Expr Purif. 2016 Mar;119:11-8


Patent Information:
Rare Disease
For Information, Contact:
Stephen Snider
AVP Tech Transfer
The University of Toledo
419 530 6225
Ronald Viola
Bharani Thangavelu
Qinzhe Wang
Vinay Mutthamsetty