Establishing autophagy inducers as novel therapies in cellular and animal models of Beta-propeller Protein-Associated Neurodegeneration (BPAN)
Awardee: Bertrand Mollereau
Institution: Ecole Normale Supérieure of Lyon
Grant Amount: $69,775.00
Funding Period: February 1, 2023 - January 31, 2024
Summary:
beta-propeller associated neurodegeneration (BPAN is the most recently identified sub-type of neurodegeneration with brain iron accumulation (NBIA) and there are currently no effective treatments for the disease. BPAN is caused by mutations in an autophagy gene WDR45. Autophagy is an important mechanism regulating neuron survival. Defective autophagy has been observed in several BPAN cellular and models and it was proposed that reduced autophagy could be responsible for neurodegeneration in BPAN patients. Hence, identification of novel therapeutics that restores a functional autophagy constitutes research priority. We have previously identified small molecule compounds that correct autophagy in cultured cells isolated from BPAN patients. We now propose to further develop test and validate the most promising hits. For this purpose, we have developed an animal fly model of BPAN disease exhibiting hallmarks of the disease, such as autophagy defect, iron accumulation, neurodegeneration and locomotor disorder. We will select the best molecule compounds restoring autophagy in human cells to rescue the cellular and locomotor defects them in BPAN flies. From our study, the most promising compounds will then be ready to be tested in a larger animal, with an ultimate aim of clinical translation and tangible patient benefit as soon as possible.