Chemical inhibition of TGS1 as therapeutic treatment for telomeropathies
The present invention consists in the pharmacological inhibition of the TGS1 enzyme and consequent elongation of telomeres, potentially able to effectively counteract the progression of pathologies caused by short telomeres. The sinefungin compound is used to inhibit the activity of TGS1, a gene that negatively regulates TERC(ncRNA found in eukaryotes which is a component of telomerase, an enzyme used to extend telomeres). The result is an increase in telomerase activity and the elongation of telomeres.
The composition contains Sinefungin, an inhibitor of the TGS1 enzyme (Trimethylguanosine synthase1). TGS1 negatively regulates the dosage of TERC, the RNA component of telomerase. The compound used in our treatment competes with the TGS1 substrate by inhibiting its catalytic activity. Consequently, there is a considerable increase in the dosage of TERC which causes an increase in telomerase activity and elongation of telomeres in human cells.
The invention provides a new drug therapy in diseases caused by defects in the activity of telomerase or in any case in diseases characterized by short telomeres, including congenital dyskeratosis and idiopathic pulmonary fibrosis. It therefore represents a new therapeutic strategy for telomeropathies. Now, transplantation represents the only hope of alleviating the specific effects caused by tissue damage following the reduction of the replicative potential of different types of stem cells, of the hematopoietic lineage. The invention has a TRL of 3.
- In dyskeratosis congenita (DC);
- In aplastic anemia;
- In idiopathic pulmonary fibrosis;
- In the Hoyeraal – Hreidarsson syndrome;
- In genetic diseases sharing a similar primary defect: telomeres. excessively short and strong reduction of the replication potential of different types of stem cells.
- Direct action on the primary causative factor, ie short telomeres;
- Potentially able to effectively counteract the progression of pathologies caused by short telomeres.