The Cystic Fibrosis Foundation has announced a grant of up to $11 million to drug research firm Icagen for a multiyear drug discovery program focused on identifying and developing treatments for people with cystic fibrosis who have "nonsense mutations" — genetic mutations in a DNA sequence that result in a shorter, unfinished protein product.
Cystic fibrosis occurs when the CF transmembrane conductance regulator (CFTR) protein is either not made correctly or not made at all. Nonsense mutations (also known as "x" or "stop" mutations) in the CFTR gene cause the production of CFTR protein to stop prematurely, which leads to a shorter, incomplete protein that either does not work or is unstable and is quickly destroyed by the cell. About 5 percent of people with CF carry two mutations that do not generate a full-length CFTR protein. As a result, they are unlikely to benefit solely from existing CFTR modulator therapies that specifically target the dysfunctional protein.
The grant will enable Icagen to screen more than two million compounds to determine whether they can enable the protein-making machinery of the cell to override these premature stop signals so a full-length, functional protein can be made. The company also will use computer modeling to simulate how millions of drug candidates might work to suppress the nonsense mutations in the CFTR gene. The company plans to use the computer modeling process — a method intended to speed up drug discovery — to identify and develop "families of molecules" that are suitable to be developed into drugs.
"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," said Icagen president and CEO Richie Cunningham. "Icagen’s innovative platform is built for programs such as these to discover and advance novel therapeutic candidates for clinical development."
“CF Foundation Awards Icagen Up to $11 Million for Nonsense Mutation Research.” Cystic Fibrosis Foundation Press Release 05/01/2018.