Lysosomal Disease Network (LDN)

Lysosomal disorders (LD) are a group of approximately 70 inherited conditions resulting from defects in lysosomal function, usually the deficiency of a single enzyme required for the metabolism of lipids, glycoproteins, or mucopolysaccharides. Collectively, LD are not especially rare, and estimates suggest that roughly 1 in 5,000 newborns will be affected with one identified LD. However, each disorder occurs with a much lower frequency and along a spectrum. For example, Fabry disease occurs in roughly 1 in 40,000 live births but MPS VII occurs in roughly 1 in 250,000. Although each LD results from a unique gene mutation, at the biochemical level they share a common characteristic: the inability to clear metabolic substrate from the lysosome. Presenting symptoms vary widely among—and sometimes within—the disorders and are modified by age of onset and severity. To date, approximately a dozen LD have therapeutic options and some conditions have more than one. Many of these therapies, however, remain sub-optimal and, apart from MPS I, approved therapies are not particularly effective in treating those LD with neurologic dysfunction. Originally founded in 2003 and funded by the NIH in 2008, the Lysosomal Disease Network (LDN) has striven to mirror the historic nature of LD by advancing innovative science dedicated to the explanation of the obstacles present to developing optimal therapies for all LD. To that end, the overarching themes of the LDN are clinical trial readiness, newborn screening, long-term outcomes, and global reach. The LDN advances these goals by conducting longitudinal clinical research projects focused on clarifying disease pathology along with cutting-edge pilot studies designed to promote innovation. The continuing educational efforts of the LDN center around the training of new fellows with an interest in LD.

The Lysosomal Disease Network (LDN) is part of the Rare Diseases Clinical Research Network (RDCRN), which is funded by the National Institutes of Health (NIH) and led by the National Center for Advancing Translational Sciences (NCATS) through its Office of Rare Diseases Research (ORDR). LDN is funded under grant number U54NS065768 as a collaboration between NCATS, the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). All RDCRN consortia are supported by the network’s Data Management and Coordinating Center (DMCC) (U2CTR002818). Funding support for the DMCC is provided by NCATS and NINDS.