Danon Disease Natural History Study

An Observational Study of Genetic Cardiomyopathy, Danon Disease

The goal of this international observational study is to learn about the natural history of Danon disease in male patients (≥8 years of age) and female patients (8 to 50 years of age).

This is an international observational study with both retrospective and prospective data collection. The study is designed to describe the natural history of Danon disease, a rare X-linked genetic disorder, and one of the most severe and penetrant forms of inherited cardiomyopathy. This study will collect data about the clinical course of Danon disease, including signs and symptoms, key clinical events, and the impact of the disease on quality of life as managed with the current standard of care. A hybrid (retrospective and prospective data collection) approach is being used to generate robust and longitudinal data. A subset of patients will be used as an External Control Arm for comparison to RP-A501 Trial participants.

Prospective Cohort:

1. Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene by a CLIA-certified genetic testing laboratory

2. Patient or parent/legal guardian are capable and willing to provide signed informed consent

3. Age ≥ 8 years at enrollment

   Female Prospective Cohort:

4. Evidence of left ventricular hypertrophy in the 12 months prior to or at enrollment.

   Retrospective (only) Cohort:

5. Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene by a CLIA-certified genetic testing laboratory

6. Patient or parent/legal guardian are capable and willing to provide signed informed consent, as required by local regulations

7. Age ≥ 8 years at enrollment

8. Prior cardiac transplantation or prior mechanical circulatory support

9. At least 30 days of retrospective medical records available prior to cardiac transplantation or mechanical circulatory support

   Female Retrospective (only) Cohort:

10. Prior evidence of left ventricular hypertrophy.

Key Exclusion Criteria:

All Cohorts:

1. Concurrent enrollment in any other clinical investigation involving use of an investigational agent for any condition at time of enrollment to this study that could confound interpretation of this study

2. Previous treatment with a gene therapy

   Prospective Cohort:

3. Prior mechanical circulatory support at time of enrollment to this study

4. Prior cardiac transplantation at time of enrollment to this study

   Female patients:

5. Age >51 years at enrollment