Connecting Function to Pathophysiology for Innovative Therapies

With more than 80 rare inborn diseases of the lysosome and lysosome-related organelles, the lysosome is crucially implicated in several widespread diseases as well as numerous pathological processes - not least, neurodegeneration. Advances in cell biology, informed in part through intensive research into lysosomal diseases, has shown the central role of the lysosome in metabolism. The lysosome is no longer a lowly body rich in acid hydrolases engaged solely in the constitutive recycling of spent components, this near-ubiquitous organelle has functions in metabolic survival, proliferation, defense, energy-sensing and the adaptive provision of materials essential for manufacture. In essence, the lysosome is a highly dynamic structure subject to regulatory control mechanisms operating at the heart of the cellular economy. With the striking success of cell-targeted enzyme therapy to augment the defective acid hydrolase in Gaucher disease, radical correction of other lysosomal diseases has become an idée fixe. Until now, the orphan drug legislation has encouraged massive investment predicated on these ultra-rare diseases. However, the real-world outcomes of approved drugs are often less than promising: efficacy varies depending on the approach the intrinsic complexities of each disease. Very few treatments mimic what has been achieved for Gaucher disease – but even here, the neurological variants are still without proven therapy. Exorbitant costs that deny access to needy patients globally, also call the extreme capitalist model into moral question. There is a pressing need for effective measures that build on scientific research that will solve genuine and persistent mechanistic hurdles that interfere with delivery and attenuate effectiveness. The 2023 Gordon Research conference on Lysosomal Diseases will cover the latest discoveries that advance knowledge about basic lysosomal function; how exactly function is impaired in lysosomal diseases - and how they inform more universal application in biology and medicine. Whenever possible, advances in science will be linked to a better understanding of the clinical phenotype and authentic therapeutic discovery. The conference is designed to attract the widest participation from molecular cell biologists, geneticists, clinical investigators and biochemists – it will particularly reward those who seek to understand the value of rare treasure beneath the surface of the lysosomal diseases.