In 2018 and 2019, GENIRIS and AFM TELETHON have decided to support with 85 000 euros Pr Aberdam project on aniridia «MODELING OF HUMAN ANIRIDIA AND GENE THERAPY APPROACHES ».
His group has designed an unique cellular model that recapitulates in vitro ARK. By the use of Crisp/Cas9 technology, a nonsense mutation found in aniridia patients has been inserted into one allele of the PAX6 gene into human limbal stem cells. It reproduces the PAX6 haploinsufficiency characteristics of aniridia.
This cellular model allowed identifying altered function in these mutated cells. Remarkably, these defects were all corrected by treatment of the mutant cells with recombinant PAX6 protein.
Moreover, the scientists identified 2 small compounds by high throughput screening that rescue defective cell migration and proliferation.
These drugs are already used for severe human depression and thus could be repurposed for ARK treatment provided that they will be validated in vivo.