Cystic Fibrosis Foundation Awards $11M to Develop Therapies for Patients with Nonsense Mutations

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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AGTR2 and lung disease in CF

The Cystic Fibrosis Foundation will award up to $11 million to Icagen to support a multi-year research-program aiming to develop new therapies for patients with cystic fibrosis (CF) caused by nonsense mutations, who may fail to respond to the current CFTR modulator therapies.

The aim of the research is to develop tailored therapies for CF-caused by nonsense mutations that will markedly improve patients’ quality of life and lifespans. Along with its financial support, the CF Foundation will help Icagen with its extensive expertise and resources.

CF arises when a protein called “cystic fibrosis transmembrane conductance regulator” (CFTR) does not function properly, either because it is abnormal or is missing entirely. Mutations in the gene coding for the CFTR protein underlie these protein defects.

Those called nonsense mutations, also known as “x” or “stop” mutations, introduce a “stop” sign before the protein is completely formed. As a result, the CFTR protein is shorter, much more unstable and targeted for destruction inside the cell.

Icagen will screen more than 2 million molecules to assess their ability to promote the cells’ protein-making machinery to overcome the premature stop signs and produce a full-length, functional CFTR protein.

The funding also will allow Icagen to use its state-of-the-art in silico drug discovery platform to assess the virtual structures of the molecules that show potential for overcoming the detrimental effects of the nonsense mutations. Their platform allows researchers to modulate 10 million possible protein structures.

The company will use a computer modeling process to identify which molecule candidates are suitable for clinical development.

“We are excited to collaborate with the Cystic Fibrosis Foundation to seek the discovery of life-transforming therapies for people with CF through this unique model. Icagen’s innovative platform is built for programs such as these to discover and advance novel therapeutic candidates for clinical development,” Richie Cunningham, president and CEO of Icagen, said in a press release.

In about 5 percent of all CF patients, the disease is caused by nonsense mutations, where they fail to generate a full-length CFTR protein. Since the currently available CFTR modulator therapies target the dysfunctional protein, patients with nonsense mutations are likely to fail to respond to this approach, highlighting the need to develop tailored therapies for these patients.