Ex Vivo Modified Hematopoietic Stem Cells to Treat Danon Disease

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Grant Award Details

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Human Stem Cell Use:
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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

  • 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.