Grace Science Foundation

THE PSYCHOGENICS INC. Team has imported and is analyzing mouse and rat models of NGLY1 Deficiency for testing of candidate therapies. First, a mouse model of NGLY1 Deficiency was used to test adeno-associated virus (AAV)-mediated gene delivery for rescue of disease-associated neurobehavioral and motor phenotypes. Team has also conducted a study using an NGLY1 knockout rat model to test phenotypic rescue using a candidate small molecule therapy (an approved drug).

THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER (YAN LAB) Team continues work generating and characterizing several mouse models of NGLY1 Deficiency, including models in which the gene is inactivated in certain tissues and conditionally after birth. These mouse models have allowed them to characterize neurological phenotypes including neuronal loss, neuropathological changes, inflammation, sensory and motor defects, and disease associated biomarkers, all of which are also observed in NGLY1 Deficiency patients These animal models provide a foundation for testing candidate therapies, including gene therapies and small molecule drugs. The team has also found that NGLY1 Deficiency in mice triggers a specific innate immune pathway mediated by the cGAS/STING pathway. Using genetic and pharmacological approaches, the team has uncovered three different targets that can be modulated to reduce disease associated phenotypes and improve survival.

CHARLES RIVER LABORATORIES Team has imported and is maintaining a colony of Ngly1 knockout rats for use in evaluating therapies to treat NGLY1 Deficiency. This knockout model has been a key foundation to test adeno-associated virus (AAV)-mediated gene delivery for rescue of disease-associated phenotypes and has supported an investigational new drug (IND) application to the FDA for an NGLY1 Deficiency gene therapy clinical study. Team has also conducted a study to monitor clinical phenotypes and collect biological samples in homozygous mutant and heterozygous (carrier) NGLY1 knockout rats across the lifespan from birth to eighteen months of age, and has continued to produce Ngly1 KO animals for use in in vivo drug testing studies.

Baylor College of Medicine (Jafar-Nejad Lab)

The University of North Carolina (Hantman Lab)

Stanford University (Dixon Lab)

Purdue University (Rochet Lab)

The Scripps Research Institute (Bollong Lab)

Hilltop Lab Animals, Inc.

Albert Einstein College of Medicine