Program areas at Grace Science Foundation
THE 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.
The T. David Gladstone Institute (Finbeiner Lab) Team has imported and is analyzing cellular phenotypes in a neuronal model of NGLY1 Deficiency to define disease mechanisms for the design and testing of candidate therapies. The team has been using robotic microscopy to investigate phenotypic differences in an NGLY1 mutant human neural cell line following differentiation from neural precursor cells to mature neurons. The team is using genetically encoded biosensors to monitor cell viability, mitochondrial shape and dynamics, proteasomal activity, autophagy flux, protein aggregation and NRF1-dependent transcriptional activity. The goal is to identify cellular changes that can be used to assess or screen for candidate drugs that can correct cellular changes caused by NGLY1 Deficiency.
The Scripps Research Institute (Bollong Lab) Team is testing the ability of small molecule modulators of the transcriptional regulators NRF1 (NFE2L1) and NRF2 (NFE2L2) for the rescue of phenotypic changes associated with NGLY1 Deficiency. The team has identified NRF1 modulating compounds that protect NGLY1 knockout cells from proteasomal stress and has been characterizing their activity. In addition, a potent and selective brain penetrant NRF2 modulating compound has been identified and is being characterized and formulated for in vivo testing. These compounds establish a proof of concept for NGLY1 Deficiency therapy development based on NRF1/2 modulation.
The University of Texas SW Medical Center (Yan Lab
The New York Stem Cell Foundation
Boston's Children's Hospital (Yu Lab)
Albert Einstein's College of Medicine-Kaushik Lab
Hilltop Lab Animals, Inc.
Baylor College of Medicine (Jafar-Nejad Lab)
Purdue University
University of Houston
The Regents of the University of California
Qiagen, LLC
Transnetyx
Genetic Alliance
BPS Bioscience
Reveal Bioscience
The Jackson Laboratory
Luna PBC, Inc.