Danon disease is an X-linked dominant cardiomyopathy caused by LAMP-2 deficiency that primarily presents with heart failure, with novel AAV vector gene therapies recently entering clinical trials.
This review summarizes the history, pathophysiology, and future therapeutic perspectives, including AAV vector gene therapy, for Danon disease, a rare vacuolar cardiomyopathy.
Danon disease, an X-linked dominant vacuolar cardiomyopathy and skeletal myopathy, is caused by a primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). This disease is one of the autophagy-related muscle diseases. Male patients present with the triad of cardiomyopathy, myopathy, and intellectual disability, while female patients present with cardiomyopathy. The disease’s leading cause of death is heart failure, and its prognostic factor is cardiomyopathy. Pathologically, the disease is characterized by the appearance of unique autophagic vacuoles with sarcolemmal features (AVSFs). Twenty-six families have been found to have this disease in Japan. It has been over 40 years since the first report of this disease by Danon et al. and over 20 years since the identification of the causative gene, LAMP2, by Nishino et al. Although the pathogenetic mechanism of Danon disease remains unestablished, the first clinical trials using AAV vectors have finally begun in recent years. The development of novel therapies is expected in the future.
Sugie et al. (Wed,) conducted a review in LAMP-2 Deficiency (Danon Disease). Danon disease is an X-linked dominant cardiomyopathy caused by LAMP-2 deficiency that primarily presents with heart failure, with novel AAV vector gene therapies recently entering clinical trials.