About the Lysosomal Disease Network

Although individually rare “orphan” conditions, the lysosomal diseases collectively affect 1 in 6,000 individuals and are responsible for a significant disability and disease burden. These diseases have become a test-bed for some of the most innovative and advanced experimental treatments, including treatment agents designed to cross the blood-brain barrier.

Even though 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 the disorders and are modified by age of onset and severity (most LD present as either a severe or attenuated phenotype); beyond categorization as severe or attenuated, a more specific genotype/phenotype correlation has not been feasible. To date, about a dozen or so LD have therapeutic options, but apart from MPS I, which has been shown amenable to stem cell transplant, LD drug therapies are not particularly effective in those conditions with neurologic dysfunction.

And while new treatments, be it next generation drug therapy, gene therapy, or other gene editing techniques, are essential to improve outcomes for those affected with LD, early detection is critical in order for a person with an LD to hope for a normal life. In the past three decades, lysosomal diseases have been a test bed for some of the most innovative therapeutic modalities. In the past 9 years of NIH funding, the LDN has accelerated knowledge acquisition in the field—with 95 NCBI cited publications—and furthered the development of therapeutic options.

For the next 5 years, the overarching thematic goals of the LDN are: clinical trial readiness, newborn screening, long-term outcomes, and global reach. We will advance these goals through clinical investigation via 3 longitudinal studies focused on elucidation of disease pathology by (a) CRIM status and immune tolerance induction in Pompe disease, (b) cardiac and kidney pathology in Fabry disease, and (c) multi-system survey (cardiac, developmental, skeletal, QOL) in the mucopolysaccharidoses. The LDN also includes a Pilot Project Program and Career Training Component.

The rarity of each lysosomal disease means that no single medical research center has an opportunity to see the entire spectrum of any one lysosomal disease, or to acquire sufficient patient numbers to adequately test new therapies. The combined and integrated efforts of the Lysosomal Disease Network focus limited resources toward creating a network of centers with expertise in these diseases in order to solve major challenges in diagnosis, disease management, and therapy. Solutions to these problems will have direct impact on patients suffering from lysosomal diseases, with important implications for medical practice and individual quality-of-life.