Development of a Gene Therapy for Treatment of Guanidinoacetate Methyltransferase Deficiency-Translating In Vivo Proof of Concept to Support a Pre-IND
Grant Award Details
Grant Type:
Grant Number:
TRAN1-16011
Investigator(s):
Award Value:
$5,145,825
Status:
Pre-Active
Grant Application Details
Application Title:
Development of a Gene Therapy for Treatment of Guanidinoacetate Methyltransferase Deficiency-Translating In Vivo Proof of Concept to Support a Pre-IND
Public Abstract:
Translational Candidate
Adeno-associated viral vector serotyped for tropism to express guanidinoacetate methyltransferase in hepatocytes and brain cells.
Area of Impact
Developing a new therapy for Guanidinoacetate Methyltransferase 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 GAMT protein in the cells of those with GAMT deficiency to effectively treat this condition. It will be delivered intravenously & target the liver primarily. Successfully restoring GAMT expression will resolve the elevated guanidinoacetic acid levels and resolve the abnormally low creatine shown to result in abnormal function of the brain of afflicted patients.
Unmet Medical Need
Guanidinoacetate Methyltransferse Deficiency results in intellectual disability, behavioral disturbances, lack of speech, and is often associated with seizures. Therapy today is all dietary which can be effective to restore creatine levels but is often minimally effective at controlling the neurotoxin GAA. 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 tropism to express guanidinoacetate methyltransferase in hepatocytes and brain cells.
Area of Impact
Developing a new therapy for Guanidinoacetate Methyltransferase 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 GAMT protein in the cells of those with GAMT deficiency to effectively treat this condition. It will be delivered intravenously & target the liver primarily. Successfully restoring GAMT expression will resolve the elevated guanidinoacetic acid levels and resolve the abnormally low creatine shown to result in abnormal function of the brain of afflicted patients.
Unmet Medical Need
Guanidinoacetate Methyltransferse Deficiency results in intellectual disability, behavioral disturbances, lack of speech, and is often associated with seizures. Therapy today is all dietary which can be effective to restore creatine levels but is often minimally effective at controlling the neurotoxin GAA. 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 GAMT.
- 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 Guanidinoacetate Methyltransferase Deficiency, are more common 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 & vendors in our state & country, including the Association for Creatine Deficiencies, for endpoint outcomes. Our efforts will support identification & inclusion of California families in pursuit of a therapy.