Raphael Thys
Understanding Senolytic Drugs and Their Potential
Senolytic drugs, which are designed to eliminate senescent cells, hold a promising future in the treatment of age-related diseases. These drugs target the Senecent Cell Anti-Apoptotic Pathways (SCAPs) and include specific inhibitors, cell therapies, and vaccines. Various senolytic drugs such as Dasatinib and Quercitin combination, Navitoclax, Fisetin, HSP90 inhibitors, FOXO4-DRI, UBX0101, USP7 inhibitors, Galactose Modified Duocarmycin, senescence-specific killing compound 1, and cardiac glycosides have shown effectiveness in eliminating senescent cells.
Senescent cells hold diverse profiles and their modulation can significantly impact age-related diseases. However, the validation of these drugs in humans remains uncertain, necessitating further research and clinical trials.
Embracing Diversity in Senescent Cell Populations
It is essential to understand the diverse profiles of senescent cells for the development of effective senolytic drugs. These cells have reached the end of their replication lifespan or have been damaged beyond repair. A comprehensive understanding of their behavior can help in developing strategies to either induce senescence to treat cancer or eliminate these cells to ameliorate aging and age-related pathologies.
Senolytic Drugs in Clinical Trials
Several clinical trials are currently underway to test the efficacy of senolytic drugs in treating various age-related diseases. For instance, the BCL-xL inhibitor UBX1325 has demonstrated significant improvements in visual acuity in patients with diabetic macular edema (DME) in a Phase 2 study. The drug is designed to inhibit the function of proteins that senescent cells rely on for survival. UNITY is actively enrolling patients for a Phase 2b clinical trial where UBX1325 is being evaluated head-to-head versus aflibercept, with 16-week results expected in Q4 2024.
In addition, an infusion of CAR T cells designed to target senescent cells has shown promise in improving metabolic function in older mice and mice prematurely aged by a high-fat diet. Researchers are eager to move these laboratory findings into clinical trials for diseases associated with aging and chronic inflammation, such as COPD, NASH, osteoarthritis, metabolic syndrome, and neurodegenerative diseases.
The Role of Artificial Intelligence (AI) in Senolytic Drug Discovery
The potential of Artificial Intelligence (AI) in identifying new senolytic drugs cannot be underestimated. A study published in Nature Communications details the use of nuclear morphology features of senescent cells to devise machine learning classifiers. These classifiers can accurately predict senescence induced by diverse stressors in different cell types and tissues. Moreover, they can be used to characterize senolytics and to screen for drugs that selectively induce senescence in cancer cells but not normal cells.
Conclusion
Senolytic drugs hold immense potential in the treatment of age-related diseases and conditions. However, the validation of these drugs in humans remains uncertain, and more investments in the field are needed. The ongoing clinical trials and the application of AI in drug discovery are expected to bring significant advancements in the field of senotherapeutics.