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An active molecule identified in baker's yeast!

BPAN (Beta-propeller Protein-Associated Neurodegeneration) is a rare and orphan disease characterized by a genetic origin due to mutations in the WDR45 gene (coding for the WIPI4 protein). Difficulties in using patient cells as research study model has made it urgent to develop simpler cell models to identify new effective treatments.

That is the reason why the french patient organisation “Autour du BPAN”, with the support of the French Foundation for Rare Diseases, has chosen to support the Dr Lasserre’s project (1), based on the use of Saccharomyces cerevisiae commonly known as baker's yeast.

Yeast is an organism that offers a very interesting study model alternative. Indeed, the conservation of genes between S. cerevisiae and human means that studies carried out on this model are suitable to the human model, and to go further, to better understand genetic human diseases (2).

The main objective of the project is a drug repurposing assay (3) to compensate for the absence of the WIPI4 protein, which production is affected by WDR45 gene mutations. The method used consists first in reproducing the pathological situation of BPAN by inactivating the gene corresponding to the human gene WDR45 in the yeast. Thereafter, researchers will test in just a few weeks and in a single manipulation a large panel of drugs (2) (see figure below). To date, a first molecule has already shown interesting results. It will be used as a positive control to test a bank of 1,300 other drugs (with market authorization), and will also be tested on patients’ cells.

Currently, a Master’s degree student, whose internship is funded by the patient organisation, is writing her bibliographic dissertation (synthesis of scientific articles and description of the research project) before starting experiments in early 2020.

(1) Dr Lasserre’s lab : INSERM U1211, MRGM Rare Diseases: Genetics and Metabolism, Bordeaux (France),
(2) Lasserre et al., 2015. Article to download here
(3) Drug repurposing consists in using pharmacological molecules already present on the market to identify new therapeutic targets.

FIG. Method for screening pharmacological drugs on yeast model mimicking the BPAN disease.
Yeasts are first grown under conditions where they can proliferate (1). They are then transferred on a solid medium offering conditions where they cannot grow (2). Sterile filters are deposited (3) and then soaked with chemical compounds (one drug per filter) (4). If a molecule is positively active, then a growth halo is observed around the filter. The targeted screening of a few drugs already allowed to identify a first active molecule on the BPAN yeast model.
mrgm autour_du_bpan fondation_maladie_rare
Author: J-P Lasserre