SP-101 gene therapy shows promise for cystic fibrosis treatment

Mary Ann Liebert, Inc.Sep 9 2024

Scientists from Spirovant Sciences describe SP-101, a novel adeno-associated virus (AAV) gene therapy for the treatment of cystic fibrosis (CF) in the peer-reviewed journal Human Gene Therapy. They also showed that after single dose inhaled delivery of SP-101, SP-101 vector genomes were detected throughout the respiratory tract of CF ferrets. 

Cystic fibrosis is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Katherine Excoffon, and coauthors from Spirovant Sciences, describe SP-101, an AAV gene therapy vector that has been optimized for efficient human airway cell transduction, and that contains a functional and regulated shortened human CFTR minigene (hCFTRΔR).

The investigators showed that hCFTRΔR mRNA expression was highest in ferrets that also received single does inhaled doxorubicin, an AAV transduction augmenter.

"SP-101 mediated hCFTRΔR mRNA expression was clearly apparent in all SP-101 dose groups 2-weeks and 13-weeks post-dose," stated the investigators.

In in vitro studies, "functional correction of CF human airway epithelia increased with increasing multiplicity of infection and doxorubicin concentration and correlated with increasing cell-associated vector genomes and hCFTRΔR mRNA expression."

A number of efforts to use AAV for CF gene therapy have fallen short on efficiency and duration of gene transfer. The vector described by Excoffon and colleagues combines a number of improvements in an attempt to overcome these obstacles and fulfill the unmet needs of CF patients for whom effective CFTR modulators are not available."

Editor in Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School