Genetically Modified Hematopoietic Stem Cells for the Treatment of Danon Disease

Danon disease is a fatal X-linked recessive disease caused by lack of expression of the lysosomal associated membrane protein type 2 (LAMP2) leading to severe vacuolar cardiomyopathy as well as multiple organs damage.  Without heart transplant, patients generally die from heart failure by the second or third decade of life. We developed a new method of re-expression of LAMP2 to heart/Cardiomyocytes, brain, liver and muscle, by transplantation gene-modified autologous LAMP2 knockout hematopoietic stem and progenitor cells to the Danon mouse model. The LAMP2 re-expression improved cardiac systolic function and behavior change. The advantage of this method is that one transplantation improves disease life long as well as with the low risk of immunological rejection with the autologous transplantation.

Our findings also provide a new paradigm for the treatment of a wide assortment of lysosomal diseases due to dysfunctional transmembrane lysosomal proteins as well as autophagy-related disorders that collectively have a major impact on public health.