Pharmaceutical composition for the treatment of cystic fibrosis

Figure 1. ASL mucus viscosity.Bars represent the average viscosity after 24 hours of incubation. Untreated CF (n=8) and non-CF (n=6) epithelia were incubated with 0.1% DMSO as control. CF epithelia were incubated with 0.25 µM of MM3 (n=7) or 0.25 µM of MM34 (n=8). Data were obtained from two non-CF donors and two different homozygous F508del-CFTR patients. * indicates p<0.05.

New and innovative aspects

There are a group of diseases related to abnormal function of channel proteins facilitating the transport of ions through biological membranes. These conditions, known as “channelopathies”, are very diverse and include cystic fibrosis (CF).

Currently, approved drugs such as Kalydeco or Orkambi target pharmacological correction of CFTR protein. However, the therapeutic outcome of these depends dramatically on the specific mutations of the patients. More than 1,700 mutations have been identified and there is a cohort of patients lacking CFTR production for whom the current strategies are not effective.

The compounds of the invention replace the faulty transport activity of the CFTR protein, providing an alternative path for anion transport through lipid membranes. This therapeutic strategy is independent of CFTR production and activity, being potentially useful for all CF patients regardless of the mutation causing CF disease.

Specifications

The compound of the invention has demonstrated to correct key functional parameters in model epithelial cultures derived from CF patients. Thus, Air surface liquid pH and volume as well as mucus rheology in CF epithelium are corrected to values comparable to those of normal tissue upon application of the compounds. Importantly the dose required to observe these effects did not induce significant cytotoxicity due to unspecific anion transport activity.

Applications

• Active pharmaceutical ingredient (API), with anionophore capacity for the treatment of patients with cystic fibrosis, regardless of the detected mutation.
• Synthesis of molecules with anionophore capacity as antimicrobial agents for the treatment of infections caused by resistant bacteria (patients with CF / without CF).
• Application in studies of correlation of cytotoxicity with anion transport activities of anionophores.
• Application in studies of anionophoreic activities that influence transmembrane pH gradients (cell membrane, intracellular compartments).
• Biosensor cell lines and cell based assays for biomembrane research.
• Nanoformulations of compounds and ion sensors assays for molecular biologyresearch.

Intellectual property status

Protected by patent PCT/EP2019/057696

Current development status

The technology related to the synthesis method is developed.

Desired business relationship

Commercial agreement; License agreement; Technical cooperation: further development; Technical cooperation: testing new applications; Technical cooperation: adaptation to specific needs.