14th May 2021 – The Lowe Syndrome Trust is pleased to announce a grant award to Purdue University USA.
The LST is awarding a 2-year project grant to Purdue to research ‘Reactivation of Ocrl1 function in Lowe Syndrome’, testing possible drugs in the laboratory to see if they could be used to help treat Lowe syndrome. Ocrl1 is the enzyme that is mutated in Lowe syndrome and it is thought specific drugs may be able to restore its function.
This award follows on from previous research projects the Lowe Syndrome Trust has contributed to for drug screening which showed certain compounds, including FDA approved drugs for other conditions, can also restore Ocrl1 kidney function. This project will assess the ability of compounds to biochemically restore the enzyme activity of a panel of Lowe Syndrome patient Ocrl1 variants and the effects upon various phenotypes.
These compounds include drugs such as Alpelisib originally designed for treating breast cancer. See Lowe Syndrome Trust news articles, 2021 Jenny Gallop Gurdon Institute, University of Cambridge & Zurich potential breakthrough on treatment for Lowe Syndrome Kidney disorder.
The research will be carried out under Dr Ruben Aguilar, Assistant Head and Showalter Faculty Scholar, Department of Biological Sciences, Purdue University, USA.
Dr Aguilar commented:
“Lowe Syndrome (LS) is a disease caused by mutations in the OCRL1 gene that unfortunately leads to the early death of affected children and has no cure. However, this project aims to change such scenario.
Our results indicate that a substantial number of patients bear Ocrl1 mutated proteins with intact enzymatic regions but locked in a non-functional structure. Therefore, we hypothesize that these Ocrl1 patient mutated proteins can re-acquire functionality by action of drugs able to stabilize their enzymatically active form. Indeed, our lab recently identified a group of compounds (including FDA-approved drugs) as able to restore the activity of different Ocrl1 patient mutants and to suppress a readout LS cellular phenotype. Nevertheless, their generalized applicability to multiple patient Ocrl1 variants and suppression of multiple phenotypes needs to be assessed and is the focus of this project. Therefore, here we will test the compounds’ ability to biochemically restore the enzyme activity of a panel of patient Ocrl1 variants and to suppress multiple patient phenotypes. This study will produce the first available Ocrl1-specific agents able to reinstate functionality; therefore, this project has a very high translational impact”.