Ex Vivo Modified Hematopoietic Stem Cells to Treat Danon Disease
Grant Award Details
Grant Type:
Grant Number:
TRAN1-15230
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$5,180,389
Status:
Active
Grant Application Details
Application Title:
Ex Vivo Modified Hematopoietic Stem Cells to Treat Danon Disease
Public Abstract:
Translational Candidate
The candidate is CD34+ HSPCs transduced ex vivo with a LAMP2 lentiviral vector.
Area of Impact
Danon Disease, Lysosomal Storage Diseases, Drug Development for Rare Disease
Mechanism of Action
Engrafted HSPC progeny will supply normal LAMP2B to the heart, liver, muscle, and brain via lysosomal cross-correction. Specifically, macrophages transfer lysosomes containing LAMP2B to cells deficient in this protein, improving autophagy and cell metabolism. This therapeutic lysosomal “cross-correction” paradigm is now well-established in the field and has already shown efficacy in lysosomal storage disorders as well as our own ongoing Phase I/II clinical study of cystinosis.
Unmet Medical Need
Most Danon patients will either die from heart failure or require heart transplantation. No specific therapies exist for other symptoms including neurodegeneration and skeletal myopathy. Hence there is a high unmet need for new therapies for this highly morbid rare disease.
Project Objective
Submission of Pre-IND materials
Major Proposed Activities
The candidate is CD34+ HSPCs transduced ex vivo with a LAMP2 lentiviral vector.
Area of Impact
Danon Disease, Lysosomal Storage Diseases, Drug Development for Rare Disease
Mechanism of Action
Engrafted HSPC progeny will supply normal LAMP2B to the heart, liver, muscle, and brain via lysosomal cross-correction. Specifically, macrophages transfer lysosomes containing LAMP2B to cells deficient in this protein, improving autophagy and cell metabolism. This therapeutic lysosomal “cross-correction” paradigm is now well-established in the field and has already shown efficacy in lysosomal storage disorders as well as our own ongoing Phase I/II clinical study of cystinosis.
Unmet Medical Need
Most Danon patients will either die from heart failure or require heart transplantation. No specific therapies exist for other symptoms including neurodegeneration and skeletal myopathy. Hence there is a high unmet need for new therapies for this highly morbid rare disease.
Project Objective
Submission of Pre-IND materials
Major Proposed Activities
- Pilot pharmacology studies of PA_001 surrogate to ameliorate DD in a mouse model of the disease.
- Drug product process and assay development towards production of a clinical-scale lot of PA_001
- Pilot safety studies of PA_001
Statement of Benefit to California:
Danon disease is a fatal disease without a cure, therefore the treatment we propose will directly benefit the citizens of California who have/will have the disease. Our findings also may assist in the development of new treatments for other rare diseases. Thus the work also has the potential to help Californians who suffer from similar conditions. This project utilizes CA scientists and laboratories. With success, it will generate additional research and employment opportunities for CA citizens.