Development of a Gene Therapy for the Treatment of Arginase Deficiency – Translating from Proof of Concept to Support Pre-IND Meeting
Grant Award Details
Grant Type:
Grant Number:
TRAN1-15227
Investigator(s):
Disease Focus:
Award Value:
$5,266,504
Status:
Active
Grant Application Details
Application Title:
Development of a Gene Therapy for the Treatment of Arginase Deficiency - Translating from Proof of Concept to Support Pre-IND Meeting
Public Abstract:
Translational Candidate
Adeno-associated viral vector serotyped for hepatic tropism to express Arginase 1 in hepatocytes.
Area of Impact
Developing a new therapy for Arginase Deficiency, where present day this is minimally effective at best.
Mechanism of Action
The proposed clinical candidate is a virus that has been altered to carry the gene for & produce the arginase protein in the liver of those with arginase deficiency to effectively treat this condition. It will be delivered intravenously & target the liver. Successfully restoring arginase expression in the liver will resolve the elevated arginine levels and resolve the abnormal arginine metabolite guanidino compounds shown to result in abnormal function of neurons & function of oligodendrocytes.
Unmet Medical Need
Arginase Deficiency results in progressive cognitive decline, often with seizures, loss of milestones & frequently with children becoming wheelchair-bound. Therapy today is all dietary which is minimally effective. This proposal is to bring to an IND an effective gene-based approach as new therapy.
Project Objective
Pre-IND meeting, then clinical trial planning.
Major Proposed Activities
Adeno-associated viral vector serotyped for hepatic tropism to express Arginase 1 in hepatocytes.
Area of Impact
Developing a new therapy for Arginase Deficiency, where present day this is minimally effective at best.
Mechanism of Action
The proposed clinical candidate is a virus that has been altered to carry the gene for & produce the arginase protein in the liver of those with arginase deficiency to effectively treat this condition. It will be delivered intravenously & target the liver. Successfully restoring arginase expression in the liver will resolve the elevated arginine levels and resolve the abnormal arginine metabolite guanidino compounds shown to result in abnormal function of neurons & function of oligodendrocytes.
Unmet Medical Need
Arginase Deficiency results in progressive cognitive decline, often with seizures, loss of milestones & frequently with children becoming wheelchair-bound. Therapy today is all dietary which is minimally effective. This proposal is to bring to an IND an effective gene-based approach as new therapy.
Project Objective
Pre-IND meeting, then clinical trial planning.
Major Proposed Activities
- Generate & characterize clinical-grade adeno-associated viral vectors for expressing ARG1 in liver.
- Characterize safety profile of intended clinical product by a toxicology study w/clinical-scale lot.
- Develop and prepare all associated documents for a Pre-IND Meeting package for FDA submission.
Statement of Benefit to California:
Genetic-based causes of intellectual disability, like Arginase Deficiency, are a more common occurrence than is appreciated by the general public, meaning there are many families in California living with these conditions. Our team will collaborate with partner organizations and vendors in our state, including the ARG1 Deficiency Foundation and patient caregivers for endpoint outcomes. Our efforts will support identification and inclusion of California families in the pursuit of a therapy.