TORC1 inhibitor against infections
On July 11, resTORbio announced the results of a phase 2a clinical trial, according to which therapy with RTB101, an inhibitor of the rapamycin complex 1 protein (target of rapamycin complex 1, TORC1), improves the function of the immune system and reduces the frequency of all types of infections, including respiratory tract infections, in people aged 65 and older. older.
The compound RTB101 tested in a clinical study is an oral drug that is a powerful selective inhibitor of TORC1. RTB101 inhibits phosphorylation of multiple targets of the TORC1-mediated signaling mechanism. Combining RTB101 with the immunosuppressant everolimus has a synergistic effect that enhances the inhibition of RTB101. According to Dr. Joan Mannick, co-founder and deputy director for Medical Affairs of resTORbio, inhibition of TORC1 increased both life expectancy and healthy life expectancy of many preclinical animal models. This was accompanied by an increase in immune, cardiac and neurological functions, which indicates the expediency of using this approach in the fight against a number of age-related diseases.
A randomized, double-blind, placebo-controlled study involved 264 volunteers aged 65 years and older who did not have unstable clinical conditions. For 6 weeks, one group of participants received the experimental drug RTB101, the second – a combination of RTB101 and everolimus, and the third – a placebo. 2 weeks after the end of the course of experimental therapy, all participants were injected with a vaccine against seasonal influenza.
The incidence of infections in the participants was assessed throughout the year, starting from the date of initiation of therapy. In the RTB101 monotherapy groups, as well as the combination of RTB101 and everolimus, there was a statistically and clinically significant decrease in the incidence of infections compared to the placebo group – by 33% and 38%, respectively. At the same time, mono- and combination therapy reduced the frequency of respiratory tract infections by 42% and 36%, respectively. The combination of RTB101 and everolimus also significantly enhanced the response to the influenza vaccine and increased the expression of key genes that ensure the ability of the immune system to protect the elderly from respiratory infections.
Respiratory tract infections are in the first place among the causes of hospitalization and the seventh leading cause of death for people aged 65 and older in the United States. Moreover, most of the respiratory infections in the elderly are caused by viruses, effective treatments for which do not exist today. If officially approved, TORC1 inhibitor therapy will become the first representative of a new class of immunotherapy that enhances the ability of the aging immune system to fight infectious pathogens, including viruses.
The company is already conducting a phase 2b clinical trial, the purpose of which is to further study the possibility of using the drug RTB101, individually and in combination with everolimus, as an immunotherapy that reduces the incidence of respiratory tract infections in elderly people at risk for morbidity and mortality from such infections. This group includes people aged 85 years and older, as well as those aged 65 years and older who suffer from combined diseases. The phase of taking the drug in this study has already been completed, and data on the results of the 16-week follow-up will be published in the third quarter of 2018.
Article by Joan B. Mannick et al. TORC1 inhibition enhances immune function and reduces infections in the elderly is published in the journal Science Translational Medicine.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru Based on resTORbio: resTORbio Announces Science Translational Medicine Publication of Phase 2a Data Showing Improvement in Immune Function and Decreased Infection Rates in People Aged 65 Years and Older.