Global Gene Therapy Clinical Trial for

Danon Disease

Now Enrolling Patients

Learn more at

Frequently Asked Questions

Why will the study only be available to a small number of Danon disease patients when it opens?

The study is investigating RP-A501, a new gene therapy that has not been previously studied in humans.  One of the most important requirements for testing of novel therapies is that there is a careful evaluation of the therapy’s safety in a limited number of patients before it can be studied in a larger population. In the case of the Danon disease gene therapy study, a lower dose of the therapy will be studied in several patients before a higher dose can be studied. Additionally, safety testing will be required in older patients (age 15 and older) before younger patients (age 8-14) can participate.  For these reasons, the study will involve several different patient groups, also known as cohorts. This type of first-in-human study, also known as a Phase 1 study, has been designed according to a format that health authorities, such as the US Food and Drug Administration (FDA) or its European counterpart the EMA, require in order to allow testing of new medications or therapies.  If the investigational therapy appears safe and potentially effective at stopping or slowing Danon disease in this initial Phase 1 study, then we will be permitted to enroll larger numbers of patients in subsequent clinical studies.


How long will the Phase 1 study last?

The Phase 1 study will enroll patients in groups of 3, and will include assessment of two different doses, and two different age groups.  If the treatment appears safe after the first 4-8 weeks in each patient group, we will be permitted to enroll subsequent groups (also called cohorts).  If side effects are relatively mild, then enrollment of all patients in the phase 1 study will occur over the course of approximately one year.  If there are side effects that are potentially more substantial, then enrollment could occur over a longer period, approximately one-and-a-half years.


Has this type of gene therapy been tested in other disorders?

Yes. Adeno-associated viruses (AAVs) have been studied in patients with many different conditions, including disorders of muscle, nerve and eye. There is one AAV product approved by the US Food and Drug Administration (FDA) for treatment of a vision disorder. The specific subtype of AAV utilized in the Danon disease study is known as AAV9. Intravenous injection of AAV9 has been studied in over 50 patients worldwide as of March 2019, including 12 patients who received a high dose of AAV9 equivalent to the higher dose planned for the Danon disease phase 1 study. These were pediatric patients with a condition known as Spinal Muscular Atrophy Type I (SMA-I); the side effects of the AAV on that study were considered modest and development of that treatment continues.


Will Danon disease patients who have had a heart transplant be allowed to participate?

Unfortunately, not in this initial study. Although it is understood that heart transplant is not necessarily curative in Danon disease, the study will need to focus on patients who have not had a prior organ transplant. This is an early, first-in-human study, and we are required to demonstrate acceptable safety of this new investigational treatment before additional studies can be conducted.  For these reasons, patients in the initial study cannot have too many additional medical conditions, including an organ transplant, because these patients are at higher risk of potentially dangerous side effects. This is also why patients with substantial blood, liver or kidney abnormalities will not be eligible for participation. Until we are able to understand the side effects in patients who do not have additional conditions (such as transplant), we will not be able to study the treatment in more advanced or complicated situations.


What do the liver enzyme numbers (AST/ALT) need to be in order for patients to be eligible for the study, and what are the reasons for these restrictions?

To be eligible for the study, a patient’s liver enzymes (AST or ALT, or SGOT/SGPT, also known as transaminases) must be lower than 10 times the upper limit of normal for the laboratory at which they were performed. This restriction is a safety measure.  The investigational therapy is a modified virus known as an AAV (adeno-associated virus). Although AAVs have been tested in patients with nerve, muscle and blood disorders in recent years with limited side effects, one side effect that has been seen in some patients is an increase in liver enzymes. These increases have been modest, and are believed to occur because the AAV often enters liver cells and can cause an immune reaction in the liver. The reactions seen in other AAV studies have not been severe. However, patients in those studies have not had disorders that affect the liver. It is thought that the increased liver enzymes in Danon disease may in part be caused by muscle involvement but it is also known that Danon disease affects the liver.  If we are able to test the investigational therapy in patients with more limited liver enzyme increases (less than 10 times upper limit of normal) and to demonstrate safety, we will then be able to test the therapy in patients with higher elevations. This is also why patients on the study will be given the steroid medicine prednisone during the weeks following the investigational treatment. 


Why are steroids being given as part of the study?

The investigational therapy is a modified virus known as an AAV (adeno-associated virus). Although AAVs have been tested in patients with nerve, muscle and blood disorders in recent years with limited side effects, they can cause an immune response against any cell in the body that they have entered; often this occurs in the liver because AAV very frequently enters liver cells. Corticosteroids, such as prednisone, have been shown to prevent or decrease this type of immune response, and for this reason many of the clinical studies testing AAV therapies incorporate steroids to prevent side effects. Patients participating on the study will be given prednisone (or a similar medicine) starting the day before the investigational therapy and for several weeks after. After 8 weeks, the prednisone will be given at gradually lower doses until it is stopped completely; this could occur sooner or later depending on side effects and liver enzymes. Patients on the study will also be given medicines to prevent prednisone side effects, including an antibiotic, and medicines to prevent stomach irritation and constipation.


What about female patients, and boys younger than 8 years?

Danon disease affects both males and females, but it generally causes an earlier and more severe illness in boys and men relative to girls and women. It also may involve different organs and cause different forms of heart disease. For these reasons, the investigational therapy may have different effects in males relative to females. In order to study these effects carefully, it makes sense to perform separate studies. The first study will be in male patients, who are at highest risk for being harmed by Danon disease. If we are able to demonstrate safety and an early indication that the treatment is slowing or stopping Danon disease, we hope to then be able to test the therapy in females. If the investigational treatment appears safe and potentially effective in this initial study, we will be able to study it in a broader population, which may include females, boys younger than 8, or patients with higher liver enzymes.


Will patients have to stop heart medications or other medicines while they are receiving treatment on study?

No. Patients will be able to continue all of their medications while participating on the study. There may be restrictions on other investigational medicines, but not on standard heart or other medications.


Will the treatment have any effect on WPW or other abnormal electrical conduction pathways in the heart?

It is hoped that the investigational therapy will prevent additional progression of Danon disease in the heart, and that it may even improve aspects of existing heart thickening. It is not known whether the treatment will improve existing electrical abnormal pathways. For that reason, patients will need to be followed carefully for Danon disease-related heart rhythm problems. It is hoped that the investigational treatment will prevent further progression of these heart rhythm difficulties. 


What is the process by which a patient is evaluated to be considered eligible for the study?

Initial contact with the principle study investigator, Dr. Barry Greenberg, and his research team at University of California San Diego, is likely to occur by telephone or email. Any patient who is interested in the study and would like to be considered may contact the study team to inquire about participation. It is very likely that the team in San Diego will need to review medical records and learn information from a patient’s local doctors.  A visit to the study center will be required to determine eligibility, and several blood, heart-imaging and exercise tests will be done over the course of 1-2 days in order to enable the study team to determine eligibility. Some of the tests may require several days before results are available, so it is likely that patients may return home after this initial visit.   

If a patient is eligible for the study and opts to participate, then a subsequent visit will be planned, likely within 2-4 weeks of the initial visit. Additional tests will be performed before the investigational therapy is administered. The therapy will be administered in a hospital setting and will involve an intravenous infusion over 1-2 hours. Patients are likely to remain in this hospital setting for 2-3 days after the infusion, and then should expect to remain in the San Diego area for 2-3 weeks after the therapy. A schedule of return visits to monitor safety and effect on Danon disease will be provided, and will include visits in the weeks and months following the investigational therapy (visits at 2, 3, 6, 9, and 12 months, 2 and 3 years after the treatment are planned).


Are patients required to pay for the travel associated with study participation?

The study sponsor, Rocket Pharma, will cover or reimburse all travel-related costs for each patient and one family member (or caregiver), including transportation to San Diego and lodging in the San Diego area.


Will the clinical trial be open to patients outside the United States?

Yes.  Patients with Danon disease who live outside the United States and are interested in participating in the clinical trial, should contact Dr. Barry Greenberg and his research team at the University of California San Diego to determine their eligibility to participate in the clinical trial.  While travel costs for the patient and one family member (or caregiver) will be covered by the study sponsor, patients should be willing to travel to the University of California San Diego for all study-related visits.


Where can patients get additional information related to the clinical trial?

More information about the trial, including how to contact Dr. Greenberg and his team can be found at

Additional questions can be sent to: