Identification of Novel Therapeutics for Danon Disease Using an iPS Model of the Disease

Identification of Novel Therapeutics for Danon Disease Using an iPS Model of the Disease

Funding Type: 
Early Translational III
Grant Number: 
TR3-05687
Award Value: 
$1,701,575
Disease Focus: 
Heart Disease
Pediatrics
Stem Cell Use: 
iPS Cell
Cell Line Generation: 
iPS Cell
Status: 
Active
Public Abstract: 
Autophagy is the cells mechanism for breaking down and recycling proteins. Danon disease is an inherited disorder of autophagy. Patients with this disease have major abnormalities in heart and skeletal muscle and generally die by the time they are in their 20s. Recently we used a new technology to turn skin cells from two patients with this disease into stem cells. The objective of our work is to use these cells to find new medications. To achieve this objective we will use techniques we helped develop to make Danon disease stem cells into heart cells. We will then screen hundreds of thousands of different drugs on these heart cells, to find drugs that make these cells work better. The most promising drugs will be tested on mice with a genetic defect that is similar to those found in patients with Danon disease. When complete, the proposed research will result in the development of a drug suitable for clinical trials of patients with Danon disease. As impaired autophagy is associated with may other diseases, including heart failure, cancer and Parkinson's disease, it is possible that the drug identified will be suitable for treatment of a variety of ailments. Furthermore, the studies will serve as proof of concept for other stem cell based drug discovery systems.
Statement of Benefit to California: 
Heart failure is among the most common reasons Californians are hospitalized, and one of the greatest expenses for the health care system. Danon disease is a type of heart failure that patients inherit. It is rare but almost always fatal. Patients who suffer from Danon disease cannot correctly perform autophagy, which is a way that cells recycle proteins. We believe that our work will help in the development of new drugs to treat Danon disease. It is also possible that the drugs we discover will be useful for the treatment of other types of heart failure. As other disease such as cancer and Parkinson's disease are associated with impaired autophagy, these drugs may help them as well. From a public health perspective, the development of new drugs for heart failure would be of great benefit to Californians. Furthermore, the work could lead to additional grants from federal agency's, as well as larger studies on patients done in partnership with industry. Such studies have the potential of creating jobs and revenue for the state.
Progress Report: 

Year 1

The goal of our project was to use stem cells to help identify new drugs for the treatment of Danon Disease, a rare, inherited disease that causes severe heart disease. Patients with Danon disease generally die in the second and third decade of life of heart failure. We have been working on this project for roughly one year. Since starting we have developed multiple stem cell lines from patients with Danon Disease. We have used these stem cells to make heart cells and have begun testing medicines on these heart cells to see if we can get them to work better. We plan in the future to identify new medicines to test any new medicines we identify on mice that have been made to mimic the disease. We are very hopeful that by the end of this project we will have come up with new ways for helping patients with this deadly disease.

Year 2

The goal of our project is use stem cells to help identify new drugs for the treatment of Danon Disease, a rare, inherited disease that causes severe heart disease. Patients with Danon disease generally die in the second and third decade of life of heart failure. We have been working on this project for roughly two yeara. Since starting we have developed over 7 stem cell lines from patients with Danon Disease. We have used these stem cells to make heart cells and have screened hundreds of drugs on these cells. We have identified several drugs using this system that show some promise and are undergoing more rigorous testing. We have also begun working with mice that have been genetically engineered to model Danon disease. We hope that these mice can be used to test out the new drugs we have identified using our stem cell screens.

© 2013 California Institute for Regenerative Medicine