The Scripps Research Institute – Dasatinib and Quercetin

Summary

The Mayo Clinic, in partnership with the Scripps Research Institute, has discovered a combination of drugs that destroy harmful senescent cells, greatly increasing healthspan in a mouse model. These drugs, called senolytics, offer a novel method of treating age-related diseases.

One of these compounds is Quercetin, a natural antihistamine and anti-inflammatory agent that is often sold as a supplement. The researchers reported that Quercetin was effective against senescent human endothelial cells. The other compound is Dasatinib, a drug that is used in the treatment of bone cancer. It was found to be effective in destroying senescent fat cell progenitors.

Because these two compounds have different strengths, the researchers chose to test the two in combination. This combination strengthened mice that were weakened by radiotherapy treatment, extended the health of mice with accelerated aging, and improved the cardiovascular function of old mice.

While other organizations have since developed other senolytic drugs, this use of Dasatinib and Quercetin is considered to be the first attempt in the world of directly removing senescent cells.

A phase 1 human study was successfully concluded and the data published in early 2019 where Dasatinib and Quercetin were used to treat Idiopathic Pulmonary Fibrosis [3]. Phase 2 clinical trials are now being organized where larger scale randomized controlled trials for senescence-related diseases including IPF will be tested.

A phase 1 human study of Dasatinib plus Quercetin in individuals with diabetic kidney disease was completed in late 2019 with promising results. The senolytic combination was demonstrated the adipose tissue senescent cell burden within just 11 days and the proinflammatory SASP secreted by these problem cells was also reduced. The presence of adipose tissue macrophages which are recruited by the activity of senescent cells were also reduced.

References:

[1] Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658.

[2] Roos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., … & Zhu, Y. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging cell, 15(5), 973-977.

[3] Nambiar, A., Justice, J., Pascual, R., Tchkonia, T., Lebrasseur, N., Kirkland, J., … & Kritchevsky, S. (2018). Targeting pro-inflammatory cells in idiopathic pulmonary fibrosis: an open-label pilot study of dasatinib and quercitin. Chest, 154(4), 395A-396A.

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Scripps Research, Mayo Clinic Scientists Find New Class of Drugs that Dramatically Increases Healthy Lifespan

Mayo researchers demonstrate senescent cell burden is reduced in humans by senolytic drugs