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The research group of José A. Sánchez Alcázar in collaboration with José Manuel Garcia Fernandez (CSIC) and Carmen Ortiz Mellet (University of Sevilla) has patented a new composition for the treatment of lysosomal diseases (P201530471/2015). Lysosomal storage disorders describe a heterogeneous group of inherited rare diseases with loss of function of lysosomal enzymes. As a result of abnormal enzyme activity various substrates are progressively accumulated in lysosomes and other organelles as mitochondria. The clinical phenotype includes visceromegaly, neurological and bone alterations, and premature death. Currently some of these diseases only have symptomatic therapy following two therapeutic approaches: substrate reduction therapy (SRT), which inhibits the enzymes involved in the production of accumulated substrates, and enzyme replacement therapy (ERT), consisting in the exogenous administration of the active recombinant enzymes that are defective in the patients. Gaucher disease is the most prevalent lysosomal disorder storage. It is caused by mutations in the gene GBA1 resulting in insufficient or defective β-glucocerebrosidase activity. The decrease of catalytic activity results in the accumulation of glucosylceramide and glucosyl sphingolipids in the lysosomes of macrophages and visceral organs. One of the most prevalent mutations in Gaucher disease is the L444P variant, resulting in incorrect folding in the ER and impaired transport to the lysosome. Patients homozygous for the L444P mutation have severe neurological forms of the disease. This mutation is particularly refractory to available treatments, including ERT, so there is an urgent need to develop therapeutic strategies for patients with this genotype. The present invention describes that the combination of a pharmacological chaperone and coenzyme Q10 (CoQ) in cellular models of Gaucher disease produces a higher benefit than individual treatments, representing an improved therapeutic option for the treatment of Gaucher disease, especially for the neuronopathic forms of the disease.

The research that originated the patent has been published in Scientific reports, 5:10903, 2015. Pharmacological Chaperones and Coenzyme Q10 Treatment Improves Mutant β-Glucocerebrosidase Activity and Mitochondrial Function in Neuronopathic Forms of Gaucher Disease.