Grace Science Foundation

“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.”

“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 $83,880. INCLUDING GRANTS OF $83,880. REVENUE $0.”

“Baylor College of Medicine (Jafar-Nejad Lab) Team is using genetic and pharmacological approaches to gain insights into pathways regulated by NGLY1 and potential targets for therapy development. This research has uncovered a link between NGLY1 and AMP-regulated kinase (AMPK) a critical cellular energy sensor. AMPK activity is reduced in animal models of NGLY1 Deficiency and in patient cell lines. Restoring AMPK levels or activity by genetic or pharmacological tools restores energy homeostasis in NGLY1 deficient cells and organisms. Team is researching the mechanisms and cellular contexts of AMPK regulation by NGLY1 and testing potential therapies to reverse AMPK-associated pathologies in NGLY1 Deficiency. EXPENSES $50,734. INCLUDING GRANTS OF $50,734. REVENUE $0.”

“Massachusetts General Hospital (Ruvkun Lab) Team continued their analysis of the genetic modifiers of proteasome dysfunction that they previously identified in PNG-1 / NGLY1 deficient C. elegans. They have continued to characterize pathways that can be targeted to restore function in NGLY1 deficient animals, insights that could translate into a potential therapy for the disease in humans. They have uncovered links between NGLY1/NFE2L1 and energy homeostasis, protein synthesis, nucleotide levels, and endoplasmic reticulum (ER) stress. These data highlight pathways for therapy development and suggest possible links to more common neurodegenerative diseases. EXPENSES $51,303. INCLUDING GRANTS OF $51,303. REVENUE $0.”

“The University of Massachusetts Medical School (Gao and Wang laboratories) Team has imported and characterized a novel mouse model of NGLY1 Deficiency, developed at the University of Texas Southwestern (Program 2 above) for use in complementary studies evaluating AAV-mediated gene therapies for treatment of NGLY1 Deficiency. In this model, the Ngly1 gene is inactivated after birth, which will permit studies that evaluate therapeutic benefit at different times and with different routes of treatment administration. EXPENSES $32,525. INCLUDING GRANTS OF $32,525. REVENUE $0.”

“The University of California at Davis (Cortopassi Lab) Team is evaluating the effect of NGLY1 Deficiency on mitochondrial function using patient-derived cellular models. They have imported and characterized NGLY1 patient and control fibroblast cell lines, and demonstrated reduced mitochondrial function and mitochondrial content relative to control lines. Team is evaluating the effect of NFE2L2 activator compounds and other tool compounds known to enhance mitochondrial activity for their ability to rescue NGLY1-dependent mitochondrial deficits. EXPENSES $25,000. INCLUDING GRANTS OF $25,000. 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. Work has begun to use these model systems to test drug candidates for their ability to rescue NGLY1 Deficiency-associated neurological symptoms and establish a framework for eventual human clinical trials. EXPENSES $35,290. INCLUDING GRANTS OF $35,290. REVENUE $0.”

“Description:consulting total fees:116829”