Drosophila models of oculopharyngeal muscular dystrophy (OPMD) included in study seeking therapeutic strategies for treating prion diseases

Neurotherapeutics. 2021 Feb 2. doi: 10.1007/s13311-020-00992-6

Anti-prion Drugs Targeting the Protein Folding Activity of the Ribosome Reduce PABPN1 Aggregation

Bamia A, Sinane M, Naït-Saïdi R, Dhiab J, Keruzoré M, Nguyen PH, Bertho A, Soubigou F, Halliez S, Blondel M, Trollet C, Simonelig M, Friocourt G, Béringue V, Bihel F, Voisset C

From the abstract: Prion diseases are caused by the propagation of PrPSc, the pathological conformation of the PrPC prion protein ... and no therapeutic solution is currently available. We thus sought to identify new anti-prion molecules and found that flunarizine inhibited PrPSc propagation in cell culture and significantly prolonged survival of prion-infected mice. Using an in silico therapeutic repositioning approach based on similarities with flunarizine chemical structure, we tested azelastine, duloxetine, ebastine, loperamide and metixene and showed that they all have an anti-prion activity. ... Strikingly, some of these drugs were also able to alleviate phenotypes due to PABPN1 nuclear aggregation in cell and Drosophila models of oculopharyngeal muscular dystrophy (OPMD). These data emphasize the therapeutic potential of anti-PFAR drugs for neurodegenerative and neuromuscular proteinopathies.

DOI: 10.1007/s13311-020-00992-6
PMID: 33533011