Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal inherited neurodegenerative disease of children and in 1998, Dr. Peter Lobel and I identified the genetic basis for this disease as mutations in the gene encoding the lysosomal protease, tripeptidyl peptidase 1 (TPP1). Subsequent research in our laboratory focused on developing potential treatments for this disease, and we established a collaboration with BioMarin Pharmaceuticals that culminated in the FDA and EMA approval in 2017 for cerebroventricular administration of recombinant TPP1 (Cerliponase alfa or Brineura™). This is the first effective treatment for LINCL and currently the only approved treatment for a neurological lysosomal storage disease. Our laboratory continues to search for improved treatments for LINCL and related diseases. In addition, as part of our long-term interest in the basic biology of the lysosome, our laboratory implemented cutting-edge mass spectrometry methods and we use these to investigate lysosomal diseases to identify proteomic changes that could provide insights into pathogenic pathways, and to identify protein biomarkers with potential clinical value.
