Monday, January 23, 2023
A Gene-Edited Cell Therapy for an Incurable Disease: Researchers Receive USD 4.8M Grant to Treat Friedreich’s Ataxia
By: Rebecca Roberts - Jan. 23, 2023. Professor Stephanie Cherqui of University of California San Diego’s School of Medicine recently received a prestigious grant from the Californian Institute of Regenerative Medicine, which will allow her and her team to bring her novel CRISPR therapy for the fatal neurodegenerative disease Friedreich’s ataxia to the clinic. Cherqui’s novel treatment for FRDA is an ex vivo gene-edited autologous cell therapy. The process begins with extracting haematopoietic stem and progenitor cells (HSPCs) from the peripheral blood of patients before excising the trinucleotide repeat hyperexpansion in intron 1 of the FXN gene from the cells.
This edit involves delivering a ribonucleoprotein (RNP) complex consisting of Cas9 and two sgRNAs – one guide for either end of the trinucleotide expansion. In their original proof-of-concept study, the team were able to achieve editing efficiencies of more than 50% in the HSPCs of FRDA patients. Edited HSPCs display restored expression of frataxin and mitochondrial function, and can be transplanted back to patients as a one-time, curative therapy.
»Because this mutation is located within an intron in the FXN gene, it is a good target for gene correction by removing this expansion using CRISPR-Cas9. In addition, this approach would be valid for all FRDA patients, because they all carry a trinucleotide expansion mutation,« Cherqui elaborates.
Edited HSPCs are currently used for the treatment of blood disorders such as sickle cell disease and β-thalassemia. However, Cherqui’s work is novel because it offers proof that these cells can be used to treat conditions like FRDA. Edited HSPCs are able to proliferate and differentiate into macrophages and microglia in vivo in mice, and traffic to the necessary tissues throughout the body and brain of FRDA patients.
The early data shows that transplantation of the corrected HSPCs in mice prevents disease progression. The therapy will be aimed at the treatment of babies and children in whom the disease has not yet caused significant damage, however, Cherqui says they may also be able to halt disease progression in adult patients.
