Grace Science Foundation

“The president of the foundation has immaterial ownership interest, in the investments of fortress and silverlake, which are managed by two of the directors.”

“The president of the foundation has authority to elect one or more members of the governing body.”

“The governing body of the foundation did not meet during the year.”

“The foundation does not have any committees.”

“Prior to filing form 990, the foundation's president will review the form.”

“AVAILABLE UPON REQUEST.”

“AVAILABLE UPON REQUEST.”

“The mission of the foundation is to support and fund the development of life-saving treatment for patients that are deficient in the n-glycanese enzyme and those suffering from related genetic diseases. The activities of the foundation will involve providing grant funding to hospitals and medical research facilities which are conducting medical research in various fields relating to the search for understanding and treatment of this condition, and fostering collaboration between academia, research institutions, hospitals, private companies, and governmental agencies.”

“Baylor College of Medicine NGLY1 Natural History Study (Bernhard Suter)Team is conducting a natural history study to define the clinical spectrum of the disease and its progression, and define biomarker endpoints for use in therapeutic trials. This study is led by Dr. Bernhard Suter, MD, a child neurologist and medical geneticist. The study is collecting longitudinal measures of movement concurrently with clinical and biomarker measures to define aspects of gait and movement that are most affected in the disorder, characterize progression of the disease, select clinical features for performing longitudinal assessments, and inform clinical endpoint development for therapeutic trials. EXPENSES $452,697. INCLUDING GRANTS OF $452,697. REVENUE $0.”

“Psychogenics Inc. Team has imported and is analyzing mouse and rat models of NGLY1 Deficiency for testing of candidate therapies. Team has conducted several studies using an NGLY1 knockout rat model to test phenotypic rescue using candidate small molecule therapies (both novel and approved drugs). EXPENSES $352,945. INCLUDING GRANTS OF $352,945. REVENUE $0.”

“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. EXPENSES $203,574. INCLUDING GRANTS OF $203,574. REVENUE $0.”

“The University of North Carolina (Hantman Lab) Team has utilized a mouse model on NGLY1 Deficiency to analyze directed movement behavior and identify the affected brain circuits responsible for the movement phenotypes charcateristic of NGLY1 Deficiency. The studies involve training wild type and Ngly1-deficient mice to perform a "reach-grab" task, comparing the task performance and movement dynamics between typical and affected animals, and recording from specific brain circuits while the animals perform the task. Identified changes will help to better understand the neural basis of the NGLY1 Deficiency movement disorder, define the neural circuits that must be targeted to treat the disease, and establish a platform to test potential therapies. EXPENSES $80,637. INCLUDING GRANTS OF $80,637. REVENUE $0.”

“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. EXPENSES $68,025. INCLUDING GRANTS OF $68,025. REVENUE $0.”

“Boston Children's Hospital (Yu Lab) TEAM HAS CONCEIVED AND TESTED METHODS TO USE DESIGNER ANTISENSE OLIGONUCLEOTIDES (ASOS) TO INHIBIT POTENTIAL TARGETS FOR NGLY1 THERAPY DEVELOPMENT. THIS RESEARCH HAS DEVELOPED CELLULAR MODELS TO MEASURE INHIBITION OF A SPECIFIC GENE TARGET WHOSE INACTIVATION HAS BEEN SHOWN TO R ESCUE NGLY1 LOSS. PILOT SCREENS WERE CONDUCTED AND OPTIMIZED ASOS HAVEBEEN IDENTIFIED. TEAM IS RESEARCHING METHODS TO ASSESS RESCUE OF NGLY1 DEFICIENCY PHENOTYPES UPON ASO TREATMENT. EXPENSES $49,108. INCLUDING GRANTS OF $49,108. REVENUE $0.”

“Hilltop lab animals, inc. Team has imported and established a colony of ngly1 knockout mice for use in testing therapies to treat ngly1 deficiency. A breeding colony has been established, and mutant phenotypes have been characterized. This model system has been used to test drug candidates for their ability to rescue ngly1 deficiency-associated neurological symptoms and for genetic studies to test whether blocking other pathways (including fbxo6) has potential to treat ngly1 deficiency. Expenses $27,695. Including grants of $27,695. Revenue $0.”

“Albert einstein college of medicine (kaushik lab) team is testing the hypothesis that defects in ngly1 function leads to the impairment of cellular proteostasis pathways that recognize and clear misfolded and aggregated proteins and defective organelles. Using ngly1 knockout rat and mouse tissues, ngly1 mutant cell lines, and ngly1 deficiency patient fibroblasts, the team has observed significant impairment in macro- and chaperone mediated-autophagy and defects in lysosomal biogenesis. These results highlight the potential of drugs that target the autophagy-lysosome pathway to reverse cellular defects associated with ngly1 deficiency. The team has begun evaluating drug-like chemical modulators of the autophagy-lysosomal system for their ability to reduce cellular proteotoxicity in ngly1 deficiency models. Expenses $24,241. Including grants of $24,241. Revenue $0.”

“Purdue university (rochet lab) team is developing and employing cellular models to test whether ngly1 and its substrate nfe2l1 have a role in modulating cellular stress and preventing or clearing protein aggregates in the brain. These studies are testing whether loss or dysfunction of the ngly1-nfe2l1 pathway may sensitize nerve cells to oxidative or protein misfolding stress, leading to neuronal damage and neurodegeneration. In addition, the team is testing the idea that enhancing ngly1-nfe2l1 activity can prevent or slow neuronal loss using cellular models of parkinson's disease, a neurodegenerative disorder associated with oxidative stress and protein aggregation. These studies aim to understand the cause of neurotoxicity in rare and common neurodegenerative disorders, explore mechanisms shared between ngly1 deficiency and parkinson's disease, and provide insights for the development of disease-modifying neuroprotective therapies. Expenses $23,869. Including grants of $23,869. Revenue $0.”

“Pharmaron, inc team has conducted pharmacology studies to support in vivo testing of small molecule therapies for ngly1 deficiency. Expenses $20,356. Including grants of $20,356. Revenue $0.”

“Universitry of utah (chow lab) team has developed and imported model organism and human cellular models of ngly1 deficiency, characterized their abnormalities and begun to use these to investigate candidate therapeutic targets of this rare disease. In particular the team is testing previously identified drug hits and inhibitors of glycogen synthase 3-beta (gsk3b) in cellular models of ngly1 deficiency, and in fly and mouse models of ngly1 deficiency. Expenses $19,321. Including grants of $19,321. Revenue $0.”

“BIOAGILYTIX LABS - vendor has conducted biomarker and immune profiling of NGLY1 Deficiency patients in support of NGLY1 Deficiency natural history studies. EXPENSES $19,000. INCLUDING GRANTS OF $0. REVENUE $0. TRANSNETYX - vendor has provided genotyping services to support animal breeding and functional studies at Hilltop Lab Animals and Psychogenics, Inc. EXPENSES $13,904. INCLUDING GRANTS OF $0. REVENUE $0. WUXI APPTEC - vendor has synthesized and characterized small molecule drug candidates for in vivo studies. EXPENSES $10,481. INCLUDING GRANTS OF $0. REVENUE $0.”

“Stanford university dixon and bertozzi laboratories) team has characterized the role of ferroptosis, a form of cell death associated with oxidative stress, in the pathologies associated with ngly1 deficiency. This study has established that loss of ngly1 or its substrate nfe2l1 sensitizes cells to ferroptosis, and this ferroptosis sensitivity can be reversed by expression of an activated form of nfe2l1 mimicking that generated by ngly1-catalyzed protein modification. These studies may help explain the causes of cell dysfunction and loss in ngly1 deficiency and suggest potential targets for candidate therapy development. Expenses $10,115. Including grants of $10,115. Revenue $0.”

“UNIVERSITY OF HOUSTON - Team has conducted a pilot movement disorder study to systematically and quantitatively assess movement disorder characteristics of individual patients with NGLY1 Deficiency. EXPENSES $9,747. INCLUDING GRANTS OF $9,747. REVENUE $0. MEDCHEM EXPRESS LLC - vendor has provided small molecule compounds for in vivo and in vitro studies. EXPENSES $5,369. INCLUDING GRANTS OF $0. REVENUE $0.”