CF Foundation Awards Research Projects to Advance Therapies for All CF Patients

The Cystic Fibrosis Foundation has awarded a total of $1.7 million in nine grants to research projects focused on tools and strategies to advance therapies for all cystic fibrosis (CF) patients, regardless of their underlying mutations.

“There has been an explosion of scientific progress in novel technologies with the potential to benefit all people with CF, yet significant additional research will be required to move these advances out of the lab and safely to patients,” William Skach, MD, the foundation’s executive vice president and chief scientific officer, said in a press release.

“These awards reflect important investments into the foundational research that is needed to advance curative therapies for all people with cystic fibrosis,” Skach added.

The awards fall under the foundation’s Path to a Cure, a $500 million initiative launched last year to promote the development of new treatments tackling CF’s underlying cause (disease-modifying therapies), with the final goal of finding a cure for the disease.

CF is caused by mutations in the CFTR gene, resulting in the production of a faulty CFTR protein. Since CFTR normally controls the flow of water through cells that produce mucus, sweat, saliva, tears, and digestive enzymes, these mutations lead to the excessive production of mucus in several organs, such as the lungs, and salty sweat.

Path to a Cure was created to promote research into three main strategies to target CF’s cause: repairing the non-functional CFTR protein, restoring CFTR protein when it’s missing, and fixing disease-causing mutations or delivering a healthy copy of the CFTR gene to cells.

Because each approach requires specific knowledge and tools, the foundation is bringing together researchers and industry leaders from various fields to advance multiple areas of research in parallel.

The nine grants will support projects from two companies and seven academic institutions with the potential to help overcome current scientific challenges in developing disease-modifying therapies for all people with CF, regardless of their CFTR mutation.

Specifically, the awarded projects will focus on improving or developing gene-based therapies and others, identifying new therapeutic targets, and developing better research tools for CF.

The foundation will grant up to $343,000 to Splice Bio, a gene therapy company, to develop a platform to produce adeno-associated viruses (AAVs) — the most commonly used vehicle in gene therapy to deliver genes to cells — that can better target specific lung cells in people with CF.

Splice Bio’s platform aims to address two existing limitations of AAVs as vehicles for gene therapy, by increasing the size of the gene that can be delivered and expanding the range of tissues that can be targeted.

The foundation’s Therapeutics Lab will collaborate with the company in this research.

In a separate press release, Miquel Vila-Perelló, Splice Bio’s co-founder and CEO said: “We are excited to work together with the Cystic Fibrosis Foundation and look forward to advancing novel gene therapies that can contribute to the development of a cure for cystic fibrosis.”

The other company receiving an award by the foundation was Rewrite Therapeutics, which will work on providing preclinical proof-of-concept for a gene-editing therapy for CF.

In contrast to gene therapy, which delivers a healthy gene copy to cells but does not affect a person’s mutations, gene-editing therapies work by correcting the person’s own mutations.

The awards given to researchers at academic institutions include:

• A project led by Adam Feinberg, PhD, of the Carnegie Mellon University, in Pennsylvania. It aims to further develop and test a platform capable of overcoming the lungs’ immune defenses to successfully deliver a new gene-based therapy to the cells that line the airways.

• A project led by Tom Harris, MD, with the University of Alabama at Birmingham, which will focus on a new approach to increase the levels of CFTR messenger RNA (mRNA), the molecule generated from the CFTR gene and used as a template for CFTR protein production. By increasing CFTR mRNA levels, researchers expect to boost the effectiveness of current and new therapies targeting this molecule to correct the non-functional CFTR protein.

• Two projects aimed at identifying new therapeutic targets and improving future therapies. Tamas Hegedus, PhD, of the Eötvös Loránd Research Network will lead work to better understand the mechanism of action of Kalydeco (ivacaftor; an approved CF therapy marketed by Vertex Pharmaceuticals). John Hunt, PhD, of Columbia University, will lead studies to deepen the current understanding of CFTR protein’s structure and function.

• Projects intending to develop scientific tools for CF, including a new way to generate specialized lung cells that produce high levels of CFTR and improved preclinical models to study extremely rare CFTR mutations. The studies will be led by Darrell Kotton, MD, of the Boston University School of Medicine and Boston Medical Center, and by Gergely Lukacs, MD, PhD, of the McGill University, in Canada.

Earlier this year, the foundation funded six research grants and five pilot and feasibility studies focused specifically on CFTR nonsense mutations, which are responsible for about 10% of all CF cases. These mutations lead to a premature stop in protein production, resulting in a shorter, non-functional or poorly functional CFTR protein.

The CF Foundation now is accepting proposals for next year’s research funding.