Help us: Donate
Follow us on:
×

Journal Club January 2019 – Senolytics for Idiopathic Pulmonary Fibrosis

Share

For the January Journal Club, we discussed the recent human senolytics trial conducted at the Mayo Clinic.

Abstract
Background
Cellular senescence is a key mechanism that drives age-related diseases, but has yet to be targeted therapeutically in humans. Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal cellular senescence-associated disease. Selectively ablating senescent cells using dasatinib plus quercetin (DQ) alleviates IPF-related dysfunction in bleomycin-administered mice.

Methods
A two-center, open-label study of intermittent DQ (D:100 mg/day, Q:1250 mg/day, three-days/week over three-weeks) was conducted in participants with IPF (n = 14) to evaluate feasibility of implementing a senolytic intervention. The primary endpoints were retention rates and completion rates for planned clinical assessments. Secondary endpoints were safety and change in functional and reported health measures. Associations with the senescence-associated secretory phenotype (SASP) were explored.

Findings
Fourteen patients with stable IPF were recruited. The retention rate was 100% with no DQ discontinuation; planned clinical assessments were complete in 13/14 participants. One serious adverse event was reported. Non-serious events were primarily mild-moderate, with respiratory symptoms (n = 16 total events), skin irritation/bruising (n = 14), and gastrointestinal discomfort (n = 12) being most frequent. Physical function evaluated as 6-min walk distance, 4-m gait speed, and chair-stands time was significantly and clinically-meaningfully improved (p < .05). Pulmonary function, clinical chemistries, frailty index (FI-LAB), and reported health were unchanged. DQ effects on circulat.ing SASP factors were inconclusive, but correlations were observed between change in function and change in SASP-related matrix-remodeling proteins, microRNAs, and pro-inflammatory cytokines (23/48 markers r ≥ 0.50).

Literature

Justice, J. N., Nambiar, A. M., Tchkonia, T., LeBrasseur, N. K., Pascual, R., Hashmi, S. K., … & Kirkland, J. L. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine.

About the author
Oliver Medvedik

Oliver Medvedik

Oliver Medvedik, Co-founder of Genspace citizen science laboratory in Brooklyn NY, earned his Ph.D. at Harvard Medical School in the Biomedical and Biological Sciences program. As part of his doctoral work he has used single-celled budding yeast as a model system to map the genetic pathways that underlie the processes of aging in more complex organisms, such as humans. Prior to arriving in Boston for his doctoral studies, he has lived most of his life in New York City. He obtained his bachelor’s degree in biology from Hunter College, City University of New York. Since graduating from Harvard, he has worked as a biotechnology consultant, taught molecular biology to numerous undergraduates at Harvard University and mentored two of Harvard’s teams for the international genetically engineered machines competition (IGEM) held annually at M.I.T. Oliver is also the Director of The Maurice Kanbar Center for Biomedical Engineering at the Cooper Union, New York City. The Maurice Kanbar Center for Biomedical Engineering is open to all Cooper Union faculty and students working on bioengineering projects requiring equipment and space for tissue culture, genetic engineering, biomechanics, and related research. Faculty that is currently using the facility are pursuing groundbreaking biomedical research in such fields as biomedical devices, tissue engineering, obstructive sleep apnea biomechanics also collaborating with several major New York City-based hospitals. The Kanbar Center continues to provide space for undergraduate teams participating in the international genetically engineered competition (iGEM) during the summer, as well as space for courses that offer a biological laboratory component.
No Comments
Write a comment:

*

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.