Large-scale biochemical screening of therapies for NGLY1 deficiency.  2017 – 2020.
In a pioneering collaboration between a patient group, government (NCATS / NIH) and the pharmaceutical industry (Retrophin), a joint three-year effort is underway to screen hundreds of thousands of small molecules for their therapeutic potential in NGLY1 deficiency. The research collaboration will focus on the development of assays for small molecule high-throughput screening in an effort to better understand the biology of the disorder, and identify potential small molecules to be developed as a therapeutic for patients living with NGLY1 Deficiency. Retrophin will seek to continue development of compounds through pre-clinical and clinical phases, with the ultimate goal of delivering a treatment option for the NGLY1 community.

Discovery of the first therapy for NGLY1 deficiency with fruit flies. 2016 – 2017.
Studies of NGLY1-deficient fruit flies reveals N-acetylglucosamine as potential therapy.

Partnering with human geneticist Dr. Clement Chow at the University of Utah, co-Investigator and Chief Scientific Officer Dr. Matt Might launched a drug discovery and validation program for NGLY1 deficiency.  After hypothesizing a potential deficiency in a N-Acetylglucosamine in NGLY1 patients, Dr. Might and Dr. Chow developed a fruit fly model of NGLY1 deficiency.  The fruit fly model had very poor survival without treatment of N-Acetylglucosamine, but quickly rose to high survival.  Human patients report tear production — in a disease where children have little or no tear production — while taking N-Acetylglucosamine.

Computational discovery of therapies for NGLY1 deficiency. 2015 – 2016.
Discovery of Prevacid as a possible future treatment for NGLY1 deficiency.

Partnering with medical chemist Dr. Kuberan Balagurunathan at the University of Utah, co-Investigator and Chief Scientific Officer Dr. Matt Might began a computational drug screening program to find small-molecule ENGase inhibitors. Work by Dr. Tadashi Suzuki has shown that removal of the gene ENGase from NGLY1 deficient mice led to significantly improved survival.  Dr. Might and Dr. Balagurunathan then confirmed a similar rescue effect in NGLY1-deficient planarian worms. They then used 3D molecular simulations to find potential drugs that could act as inhibitors of ENGase — and hence therapies for NGLY1 deficiency.  Of the 14 FDA approved compounds discovered in the screen, one — Prevacid — showed the desired activity in bench testing.  The molecular backbone of Prevacid is now being used as the backbone for the discovery of future therapeutics.