We developed a replacement strategy for this disease by designing a fusion peptide containing secretion and tissue penetrating sequences at the amino terminus of the frataxin precursor protein. Secretion and penetration of the fusion peptide was validated in experiments that confirmed its ability to localise in the mitochondria and rescue the biochemical defects and apoptotic phenotype of FRDA patient cells, in vitro. Autologous transplantation of the modified HSPCs resulted in stable secretion of the peptide in the blood stream of recipient animals, impacting disease progression by delaying the manifestation of motor-coordination/sensory symptoms, paralleled by improved biochemical and anatomical parameters.
Saturday, November 23, 2024
Therapeutic Activity of a Haematopoietic Stem Cell-Delivered Tissue-Penetrating Peptide in Friedreich's Ataxia Models
Pido, Jeffrey and Shaban, Enas and Moula, Shefta and Chritchely, Bethan and Whittaker, Thomas and Svensson, Stina and Anjomani Virmouni, Sara and Kalef-Ezra, Ester and Carr, Lucinda and Hassell, Jane and Thrasher, Adrian J. and Kurian, Manju A. and Santilli, Giorgia and Sala, Arturo and Administrator, Sneak Peek, Therapeutic Activity of a Haematopoietic Stem Cell-Delivered Tissue-Penetrating Peptide in Friedreich's Ataxia Models. doi:10.2139/ssrn.5026639
