CF Foundation Funds Three New Research Projects

As part of its Path to a Cure initiative, the Cystic Fibrosis Foundation announced three new awards to fund research projects that seek to advance the treatment of cystic fibrosis (CF).

The largest award, of up to $2.6 million, was given to Eloxx Pharmaceuticals to aid in the development of new therapies that target CF-causing nonsense mutations.

CF is caused by mutations in the CFTR gene, resulting in a loss of function of the CFTR protein that the gene provides instructions to make. A nonsense mutation is a type that results in a stop codon (a sort of “stop” signal) in the middle of a gene. This results in the production of a truncated protein that usually is non-functional and is quickly degraded by the cell.

“We feel great urgency to identify therapies that target nonsense mutations as we pursue our ultimate goal of a cure for every person with CF,” William Skach, MD, executive vice president and chief scientific officer for the CF Foundation, said in a press release.

According to the foundation, nearly 4,000 people with CF in the U.S. have at least one nonsense mutation. The most common CF-causing CFTR nonsense mutation is called G542X.

In the new project, Eloxx will screen its library of more than 2,000 compounds to identify potential agents to address CFTR nonsense mutations, specifically looking for candidates that could work in people with CF who have at least one G542X mutation.

Such agents would prompt the cellular protein-making machinery to “read through” an erroneous stop codon in the CFTR gene in order to produce a full version of the protein.

The CF Foundation awarded up to $2 million to Eloxx earlier this year to support clinical trials testing ELX-02, an investigational read-through therapy for treatment of people with CF who have at least one G542X mutation.

“The early stage research underway at Eloxx complements other Foundation-funded screening programs for nonsense mutation treatments and bolsters our scientific knowledge of these notoriously difficult-to-treat targets,” Skach said.

The other two programs funded by the foundation aim to further the development of gene therapy for CF.

In principle, gene therapy is intended to deliver a non-mutated version of the CFTR gene to cells in the lungs. However, in order to design such therapies, several obstacles must first be overcome: for instance, the lung’s natural defense systems can make it difficult to deliver a gene therapy to the appropriate cells. Additionally, CFTR is a relatively large gene, so it can be difficult to fit inside of the relatively small viral vectors commonly used for gene therapy delivery.

In one of the new projects, the foundation awarded up to $600,000 to Metagenomi toward the development of new gene-editing systems that can be delivered to lung cells more effectively.

In the other project, the foundation awarded up to $300,000 to Hunterian Medicine to help develop gene therapy vectors that can fit the CFTR gene more easily.

The foundation’s $500 million Path to a Cure initiative was launched in October 2019 and has since funded several research projects in CF.