School of Medicine

Danon disease is a congenital X-linked hypertrophic cardiomyopathy that results from mutations in LAMP2, a transmembrane lysosomal protein necessary for autophagy. The disease presents in childhood or adolescence, and life expectancy is 19 for men and 34 for women. Although Danon disease is rare, no specific therapy based on its biology is currently known. Recent in vitro studies using mouse by the Cherqui Lab have shown evidence supporting hematopoetic stem cell transplant as a novel treatment option for cystinosis. Cystinosis is a metabolic disease that arises from mutations in a transmembrane lysosomal protein - cystinosin (CTNS gene). Detailed in vitro and in vivo studies have shown that rescue of the phenotype occurs because wildtype macrophages derived from the transplanted wildtype hematopoietic stem cells can transfer lysosomes containing wildtype cystinosin directly to Ctns-deficient cells in multiple organs of the host Ctns -/- mice. Because Danon disease also arises from mutations in a transmembrane lysosomal protein, LAMP2, a similar approach could be effective in rescuing the phenotype of LAMP2 mutant mice. The Adler Lab has recently developed an in vitro cell model for Danon disease using skin fibroblasts expanded from skin biopsies from two identified patients diagnosed with Danon disease, confirmed by RT-PCR. These in vitro and in vivo models can be used show efficacy of hematopoietic stem cell transplant for Danon disease.