The researchers performed their research on a mutation in the disease, Common among certain populations such as Ashkenazi Jews. Prof. Batsheva Kerem from the Hebrew University and her team were encouraged by the research findings, and announced that "the results obtained form the basis for clinical development by the SpliSense company. The new drug under development will be given by inhalation to CF patients"
Cystic fibrosis (CF) is a shortening and life-threatening hereditary disease, caused by various mutations in the cystic fibrosis gene (CFTR). The disease severely affects many body systems and causes serious damage to the functioning of the lungs and pancreas. The damaged CFTR gene codes for a chloride (Cl) channel, located on the surface of epithelial cells along the respiratory system, digestive tract and exocrine glands. Defective activity of the CFTR channel leads to the accumulation of thick mucus, which accumulates along the bronchial tree of the lung and is a substrate for the proliferation of bacteria, impairs the ability to exchange gases, and leads to chronic lung disease which is the main cause of morbidity and mortality.
Although the disease is not contagious, it is currently considered an incurable disease. An extensive group of researchers from the Hebrew University andCompany SpliSense, In collaboration with the universities of Alabama in the United States, Emory in the United States, Paris in France, Murdoch in Australia, and the Hadassah Medical Center - Led by Prof. Batsheva Kerem from the Department of Genetics at the Hebrew University, set herself the goal of developing a new treatment for CF patients who carry several mutations for the disease. One of the mutations, defined as "3849+10 KB C-to-T", leads to the degradation of the RNA molecules from the CFTR shield or alternatively to the creation of a short and inactive CFTR protein. in fact, This mutation is the seventh most common in the US and the eighth most common in Europe, and carried by about 1600 patients CF In the world. In addition, The mutation is common among certain populations such as Ashkenazi Jews. "Since the medical treatments currently available to patients CF They only respond to some of the patients, there is a need for additional strategies to develop drugs that will respond to patients carrying mutations that do not respond to the existing drugs, including the splice mutation 3849+10 KB C-to-T", the researchers explain.
The research recently published in the scientific magazine Journal of Cystic Fibrosis focused on a unique approach based on molecules known as antisense oligonucleotides, which are able to bind to specific sequences along the RNA molecules and prevent the effect of the mutation. A scan of about 30 of these molecules in a cellular model led to the identification of a number of certain molecules, which succeeded to fix effectively the splicing pattern of the RNA and prevent the inclusion of the wrong sequence that contributes to the emergence of the disease.
After that, the effectiveness of the selected molecules was tested in the epithelial cells themselves originating from the respiratory system of CF patients, who carry at least one copy of the 3849+10kb C-to-T mutation. It was found that the selected molecules had a significant ability to correct the RNA splicing model as well as the activity of the CFTR channel. In other words, the antisense oligonucleotide molecules were able to effectively penetrate the epithelial cells, without the use of carriers that would "drive" them to the place where repair is needed, and make the necessary genetic changes in them. After examining the effectiveness of the selected molecules in different cellular systems, originating from different CF patients, The researchers identified one key molecule, which showed high efficiency in repairing the splicing model and fully restoring the normal function of the canal.
"Activity levels of theCFTR After the treatment with the found molecule, it is expected to provide a significant clinical advantage to patients and improve their quality of life," Prof. Kerem said this week. "The results obtained in the current study form the basis for the clinical development of the leading molecule by the company SpliSense. The newly opened drug will be given by inhalation to the patient CF carrying the mutation".
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