2022-11-15T23:08:10-06:00 2021-12-31 WITHUMSMITHBROWNPC 601 CALIFORNIA STREET SUITE 1800 SAN FRANCISCO CA 94108 990 2021-01-01 465727883 Grace Science Foundation % GRACE SCIENCE FOUNDATION GRAC 6507464591 1142 CRANE ST 4 MENLO PARK CA 94025 MATTHEW R WILSEY PRESIDENT 6507464591 2022-11-15 true MATTHEW R WILSEY XXX-XX-XXXX Rebecca Stidham P01406582 4154343744 2021 2022-09-23 18:48:47Z MATTHEW R WILSEY 1142 CRANE ST 4 MENLO PARK CA 94025 1327113 false X www.gracescience.org X 2014 CA THE MISSION OF THE FOUNDATION IS TO SUPPORT AND FUND THE DEVELOPMENT OF LIFE-SAVING TREATMENT FOR 7 7 0 0 0 1447474 1325647 0 0 6706 1466 0 0 1454180 1327113 1373067 885550 0 0 0 0 0 0 0 79834 227582 1452901 1113132 1279 213981 2884506 3128030 386 29929 2884120 3098101 X 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 false false 262743 262743 Stanford University NGLY1 Natural History Study (Maura Ruzhnikov) Team continues 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. Maura Ruzhnikov, MD, a child neurologist and medical geneticist focusing on the diagnosis and management of rare neurologic disorders, including genetic epilepsy syndromes, childhood neurodegenerative diseases, and undiagnosed suspected genetic conditions. As of the end of 2021, the study has collected data from more than twenty-nine patients both on-site and remote. The study has characterized development delay, movement symptoms, patient quality of life, epilepsy phenotypes, and has helped establish a biomarker that is universally elevated in patients, providing a potential tool to advance therapy development. The study has followed participants longitudinally over three years. 141560 141560 University of Texas Southwestern (Yan Lab) Team has been 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, neuropathological changes, inflammation, sensory and motor defects, and disease associated biomarkers. These animal models provide insights into the specific defects that result from NGLY1 loss and establish 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. 157500 157500 The New York Stem Cell Foundation (NYSCF) Team has developed and validated four additional patient-derived induced pluripotent stem cell (iPSC) lines to complement and expand human cell models of NGLY1 Deficiency. CRISPR-mediated genome editing was used to produce isogenic control lines to establish disease-specific characteristics. Team has further used these iPSC lines to generate human neuronal models of NGLY1 Deficiency and has begun to characterize NGLY1-dependent neuronal phenotypes including changes in cellular architecture, mitochondrial function, intracellular aggregates, neuronal activity, and patterns of gene expression. These models will be leveraged for testing potential therapies to reverse pathologies associated with NGLY1 Deficiency. 83880 83880 Stanford University (Dixon and Bertozzi labs) 50734 50734 Baylor College of Medicine (Jafar-Nejad Lab) 51303 51303 Massachusetts General Hospital (Ruvkun Lab) 32525 32525 Univ. of MA Medical School (Gao and Wang Lab) 25000 25000 The University of CA at Davis (Cortopassi Lab) 35290 35290 HILLTOP LAB ANIMALS, INC. 6274 6274 CHARLES RIVER LABORATORIES 18027 18027 VIRGINIA COMMONWEALTH UNIVERSITY 13729 13729 STANFORD UNIVERSITY 270 270 THE JACKSON LABORATORY 6265 6265 TRANSNETYX 450 450 KINSALE HOLDING 323747 323747 885550 true true false false false false false false false false false false false false false false false false false false false false false false false false false true false false false false false false false false false false false false false false false false false false true 2 0 true 0 false false false false false false false false false false false false X 7 7 true false false false false true false false false false false true false false false false false false false CA X X GRACE SCIENCE FOUNDATION 6507464591 1142 CRANE ST 4 MENLO PARK CA 94025 Matthew Wilsey President 20.0 0.0 X X 0 0 0 Egon Durban Chief Financial Officer 1.0 0.0 X X 0 0 0 KEN DRAZAN Secretary 1.0 0.0 X X 0 0 0 Pete Briger Director 1.0 0.0 X 0 0 0 Chelsea Clinton Director 1.0 0.0 X 0 0 0 J Taylor Crandall Director 1.0 0.0 X 0 0 0 Elle Stephens Director 1.0 0.0 X 0 0 0 0 0 0 0 false false false 0 1325647 1325647 0 1466 1466 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1327113 0 1466 885550 885550 0 0 0 0 0 0 0 0 0 0 50548 50548 0 6618 6618 0 0 0 0 116829 116829 1891 1891 0 2565 2565 0 0 0 0 39267 39267 0 0 0 0 0 0 327 327 0 Shipping Fees 5359 5359 0 Branding/Logo/Video/Website 113 113 0 TAXES & LICENSES 150 150 0 REIMBURSABLE EXPENSES 3915 3915 0 1113132 885550 227582 0 2884506 381790 0 2745587 0 0 0 0 0 0 0 0 0 0 0 0 0 653 0 0 0 0 0 0 0 0 0 0 0 0 2884506 3128030 386 29929 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 386 29929 X 0 0 0 0 0 0 2884120 3098101 2884506 3128030 213981 X false false false X 1677107 1157365 1522789 1447474 1325647 7130382 0 0 1677107 1157365 1522789 1447474 1325647 7130382 2507425 4622957 0 0 0 7130382 0.64835 0.62200 X RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED Hilltop Lab Animals Inc 131 Hilltop Dr Scottdale PA 15683 35290 NGLY1 CHARLES RIVER LABORATORIES INTERNATIONAL INC 251 Ballardvale Street Wilmington MA 01887 6274 NGLY1 VIRGINIA COMMONWEALTH UNIVERSITY FOUNDATION PO BOX 843075 RICHMOND VA 23284 540757884 18027 NGLY1 STANFORD UNIVERSITY 485 BROADWAY MAIL CODE 8838 REDWOOD CITY CA 94063 941156365 262743 NGLY1 Natural History Study Ruzhnikov lab NEW YORK STEM CELL FOUNDATION INC 619 WEST 54TH STREET 3RD FL NEW YORK NY 10019 202905531 157500 NGLY1 MASSACHUSETTS GENERAL HOSPITAL 55 Fruit ST Boston MA 02114 041564655 51303 NGLY1 Ruvkun lab Transnetyx 8110 Cordova Rd Ste 119 Cordova TN 38016 6265 NGLY1 BAYLOR COLLEGE OF MEDICINE ONE BAYLOR PLAZA BCM 200 HOUSTON TX 77030 741613878 50734 NGLY1 Jafar-Nejad Lab THE REGENT OF THE UNIVERSITY OF CALIFORNIA 1111 Franklin St 12th floor Oakland CA 94607 25000 NGLY1 Cortopassi lab UNIVERSITY OF TEXAS SOUTHWESTERN 5323 HARRY HINES BLVD DALLAS TX 75390 141560 NGLY1 Yan Lab STANFORD UNIVERSITY 3145 PORTER DRIVE PALO ALTO CA 94304 941156365 83880 NGLY1 Dixon & Bertozzi labs STANFORD UNIVERSITY 3145 Porter Drive Palo Alto CA 94304 941156365 13729 NGLY1 The University of Massachusetts Medical School 55 N Lake Ave Worcester MA 01655 32525 NGLY1 Gao and Wang labs Part I Description of Procedure for Monitoring Use of Funds * BEFORE FUNDING A PRINCIPAL INVESTIGATOR, THE FOUNDATION REQUIRES A DETAILED PROPOSAL WITH OBJECTIVES AND MILESTONES * THE PROPOSALS ARE REVIEWED BY THE FOUNDATION AND SCIENTIFIC ADVISORY BOARD * THE PROPOSALS ARE OFTEN REVISED SEVERAL TIMES TO GET THE CORRECT FIT * Once funded, each principal investigator submits a written summary every quarter * This update is two to three pages in length * The reports discuss progress, highlight roadblocks and identify where they need help *THE FOUNDATION STEPS-IN WHERE APPROPRIATE TO MAKE SURE OBJECTIVES AND MILESTONES ARE MET * IN ADDITION TO QUARTERLY REPORTS, THE FOUNDATION HOLDS A MONTHLY CONFERENCE CALL WHERE TWO TO THREE PRINCIPAL INVESTIGATORS PRESENT THEIR LATEST WORK * BEYOND THE ABOVE TWO INITIATIVES, THE FOUNDATION HOLDS ONE TO TWO IN-PERSON MEETINGS PER YEAR * DR. KEVIN LEE (CHIEF SCIENTIFIC OFFICER), DR. SELINA DWIGHT (PROGRAM MANAGER), AND MATT WILSEY(PRESIDENT) CONTACT RESEARCHERS AND PRINCIPAL INVESTIGATORS ON A REGULAR BASIS VIA EMAIL, PHONE, OR ONE ON ONE MEETINGS THE PRESIDENT ENSURES THAT EVERY DOLLAR IS USED TO SUPPORT THE GRACE SCIENCE FOUNDATION'S MISSION. FORM 990, PART III, LINE 1 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. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES 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. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES 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. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES 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. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES 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. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES 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. FORM 990, PART III, LINE 4D, OTHER PROGRAM SERVICES 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. FORM 990 PART IX LINE 11G DESCRIPTION:CONSULTING TOTAL FEES:116829