Personalized medicine: screening of potential drugs on patient cells
Stem cells were used to evaluate the effect of the drug
The work described in the latest issue of Nature Biotechnology (Lee et al., Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression – VM) began several years ago with the study of the possibility of testing experimental drugs on specialized diseased cells grown from induced pluripotent stem cells (iPSCs). Gabsan Lee and colleagues then removed skin cells from a person with a rare genetic disease, Riley-Day syndrome. The choice of this disease was due to the fact that it affects only one type of nerve cells, which it is almost impossible to isolate by traditional biopsy.
In experiments to test the concept, scientists using known biochemical factors (they are called Yamanaki factors) reprogrammed skin cells into induced pluripotent stem cells capable of turning into cells of different specialization, and obtained nerve cells from them.
"We can't study nerve cells directly, but this approach has allowed us to see for the first time exactly what happens during the development of the disease," says Lee.
One of the symptoms of Riley-Day syndrome is reduced pain sensitivity, only half of patients live to 30 years.
In a recent study, Lee and colleagues at Memorial Sloan-Kettering Hospital used the same laboratory-grown Riley-Day syndrome nerve cells to screen seven thousand drugs. With the help of a robot programmed to analyze their effect, scientists were able to quickly identify eight compounds for subsequent testing, and only one – SKF-86466 – showed an undoubted ability to stop or reverse the development of the disease at the cellular level.
As Gabsan Lee explained, clinical trials of SKF-86466 are impossible due to the small number of patients with Riley-Day syndrome in the world, but instead of this compound, a very similar drug can be used, approved for use for other indications.
The applied significance of Lee's experiments with co-authors goes far beyond the Riley-Day syndrome. As the scientist explains, "there are many rare (orphan) genetic diseases that will never become the object of the development of new drugs with the adopted expensive model of this process. We have shown that there may be another way to find a cure for such diseases," he concludes.
In addition, reprogrammed cells make it possible to specifically develop a treatment not only for the disease, but also for an individual patient. According to the scientist, induced pluripotent stem cells obtained from the patient's own cells can be cultured, then various drugs can be tested on this culture, as a result choosing the most effective for a particular patient, thus personalizing treatment "in a Petri dish", and not by trial and error on the patient himself.
Portal "Eternal youth" http://vechnayamolodost.ru28.11.2012