Killing cells is easy. Killing only the cells that you want to kill, while leaving all other cells untouched, is very much more challenging. The ability to do this is fundamental to much of the future of medicine, however.
The aging body contains many cell populations that cause significant harm and should be removed, including misconfigured T cells, age-associated B cells, precancerous cells, and of course senescent cells of many different types. Great benefits to health and longevity might be obtained via efficient means of targeting that enable therapies to only destroy unwanted, harmful cells.
A laboratory technician in the process of pipetting a sample. Image credit: CDC/ Von Roebuck/Lauren Bishop, Public Domain
This point is well illustrated by present efforts to selectively destroy senescent cells. Today's open access paper is one of a number of recent publications that focus on using galactose conjugation to produce prodrugs that are highly selective to senescent cells. Senescent cells produce a lot of β-galactosidase, a protein that acts to strip galactose from other molecules. It is thus possible to combine any one of a range of toxic cell-killing compounds with galactose to produce molecules that are entirely innocuous until they encounter β-galactosidase, making the therapy very specific to senescent cells.
Researchers have tried this approach with the overly toxic senolytic drug navitoclax, with some success, but one really doesn't have to be clever about the drug used. In principle any of the cytotoxic compounds employed widely in the cancer research community will work. Thus other groups have used duocarmycins, while the researchers noted here instead chose gemcitabine, and a long list of alternative options exist beyond these.
Source: Fight Aging!