ABO-401 Gene Therapy Shows Potential to Restore CFTR Function in Preclinical Study

Abeona Therapeutics‘ new gene therapy ABO-401 for the treatment of cystic fibrosis (CF) has successfully delivered a functional version of the CFTR gene to the lungs of mice with CF, according to a preclinical study.

In addition, the therapy showed the potential to restore the function of CFTR protein in cells collected from CF patients.

These preclinical findings were presented in a poster, “Identification of AAV Developed for Cystic Fibrosis (CF) Gene Therapy that Restores CFTR Function in Human CF Patient Cells” (abstract#528), during the American Society of Gene and Cell Therapy (ASGCT) 22nd Annual Meeting held in Washington, D.C.

CF is a genetic disorder caused by mutations in the CFTR gene, which provides instructions to make the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein works as a channel that transports molecules, such as chloride, and water in and out of cells.

In people with CF, this type of molecule transport is impaired, leading to a buildup of thick fluid in the lungs that makes breathing more difficult and patients more likely to develop lung infections.

ABO-401 is an investigational gene therapy being developed by Abeona to allow the delivery of a functional copy of the CFTR gene to cells in the lungs of CF patients. The therapy consists of a mini-CFTR human gene packaged inside a safe version of adeno-associated virus 204 (AAV204) , one of the company’s proprietary next-generation AIM delivery vectors.

This latest preclinical data shows that ABO-401 can successfully deliver a functional copy of the mini-CFTR human gene and induce the production of high levels of its coded protein in the lungs of mice with CF. Additionally, the AAV204 vector was able to deliver larger quantities of the modified CFTR gene compared with other viral delivery vectors commonly used in gene therapies, such as AAV6.

Treatment with ABO-401 was able to restore the function of the CFTR protein and the transport of chloride in nasal and bronchial cells collected from CF patients, who were carriers of one of the most common mutations associated with the disease — the F508 deletion.

“These encouraging preclinical data add to the growing body of evidence suggesting ABO-401 may address the challenges in lung delivery and transgene expression that have limited the advancement of gene therapy for CF patients,” Timothy J. Miller, PhD, president and chief scientific officer of Abeona, said in a press release.

“ABO-401 is a promising candidate from our AIM capsid [the protein shell of a virus] library en route to [investigational new drug]-enabling studies that may ultimately change the landscape of CF treatment by introducing one-time gene therapy,” Miller said.