A growing wait list is creating additional stress on patients needing organ transplants. These patients are increasingly desperate according to an article recently published in Genetic Engineering & Biotechnology News.
Not only is the wait list growing, but the existing donor organs are getting older and less effective. Many donor organs are at a point where they can no longer be used for transplantation.
Yet the mid-range donor organs put the patients at risk for transplant rejection. This is due to their age-related response and subsequent adverse events.
The FDA Approved a Senolytic Drug
A new study confirmed that in order to be deemed transplantable, an organ need not be “young” but “youthful”.
Now the door is open for the newly-approved antibiotic azithromycin, a senolytic drug that treats age-related issues. The findings were announced by investigators at the Brigham and Women’s Hospital (BWH) in Boston, Massachusetts.
Biological aging (senescent) cells grow in the older organs. As they age, they opt out of the cell cycle. They no longer perform functions that are useful. They do not die, but they do secret inflammatory substances. Senolytic drugs eliminate these senescent cells.
A Closer Look at Cellular Senescence (CS)
BWH investigators discovered that CS (when cells stop dividing) has detriments as well as benefits for the organism in which they live.
Current research found that depending on several factors, CS can either have a positive effect by promoting tissue repair or the negative effect of causing cancer.
The burdens of CS are seen in an increase of mt-DNA (cell-free mitochondrial DNA). Mt-DNA can produce an immune response (immunogenic) leading to organ failure/rejection.
The senolytic drugs, however, cause senescent cells to reenter the cell cycle. This in turn allows their clearance from the body. Senescent cells are a source of mt-DNA.
Experimental Models of Donor Animals
Investigators used quercetin and dastinib senolytic drugs to treat old donor animal models. The results were a lessening of immune responses and survival of cardiac allografts (transplants) that compared favorably to newer donor organs.
It is noteworthy that these experiments have thus far been carried out on mouse models. The researchers have just begun their investigation on humans and already find that increased levels of mt-DNA, just as in mouse models, circulate in older donors.
The next step is to evaluate whether senolytic drugs have a similar effect on humans. So far data provides a rationale for conducting clinical trials utilizing senolytic drugs.
If successful, older organs can be utilized safely and the researchers will have reduced the demand for organ donors.
