A Pluristem bio-reactor in action.
(photo credit: PLURISTEM THERAPEUTICS INC.)
Acute radiation syndrome (ARS) resulting from terrorist activity using “dirty” bombs or accidents at nuclear reactors and other facilities can be successfully treated, thanks to an innovative stem-cell therapy developed by Pluristem Therapeutics Inc. in Haifa.
The American government is especially keen to have a quick and effective solution to radiation poisoning, both intentional and accidental. As a result, Pluristem’s PLX-R18 treatment for ARS is in advanced stages of development and clinical testing in collaboration and with the support of the US National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID).
Pending successful completion of a pilot dose-selection trial and a pivotal trial, the Israeli company plans to apply to the US Food and Drug Administration to approve commercialize of this product independently for this indication. This program is developed via the FDA Animal Rule regulatory pathway which allows for approval of treatments for diseases such as ARS in which human trials are not ethical or feasible. With this pathway, the FDA uses animal efficacy studies and human safety data as the basis for product approval.
Pluristem Therapeutics Inc., located at the MATAM industrial park in Haifa, was launched 13 years ago with only 10 employees. Slowly but surely, the now-public company has become a $130 million enterprise with 180 engineers, physicians, biologists and other professionals. It has collected donated placentas from women undergoing planned cesarean sections in two of the city’s hospitals, and uses bioreactors to grow stem cells and process them to produce an innovative drug-delivery platform.
ARS is an illness caused by the irradiation of all or most of the body by a significant dose of penetrating radiation over a very short period, with exposure being for as little as a few minutes.
Acute and intense exposure to radiation cause immature parenchymal stem cells in certain body tissues to be depleted. This can damage the bone marrow, which then prevents the body from producing the blood cells it needs to fight infection and bleeding.
As PLX-R18 has been shown to trigger the production of red and white blood cells and platelets – rescuing the hematopoietic cells and the recovery of the production of these cells by the body – if treated within 48 hours of the first exposure to ionized radiation, the product is a perfect antidote to high-level radiation exposure.
The company’s PLX-R18 cells accomplish this apparently by secreting cytokines and chemokines into the blood. Animal studies have shown an impressive nearly 100% recovery rate. Control groups given a placebo showed only a 30% recovery rate.
Among the journals that have published studies showing the successful mitigation of lethal radiation syndrome in rodents by intramuscular injection of PLX-R18 is the prestigious, open-access PLoS (US Public Library of Science).
An article in that journal reported that doctors agree treatment for radiation should begin within a few hours of exposure so that the cells are protected and prevented from dying: “This leaves no practical solution for circumstances of a nuclear disaster with no accurate estimation of the high dose exposure, where the treatment may reach the affected individuals even days after a high-dose exposure.”
But as the Pluristem solution does not require such exposure estimates, there is no barrier to immediate treatment. The first injection is given within 48 hours, followed by a second shot five days after exposure to the radiation.
PLX-R18 cells release a combination of therapeutic proteins in response to a damaged or poorly functioning hematopoietic system; this system creates the blood cells that protect us from infection, uncontrolled bleeding and anemia.
Now that Donald Trump has become US president and vows to rebuild the US military establishment, the Israeli company could benefit from an increased American military budget and the need to secure an inventory of treatments to ward off potential radiation and biothreat hazards, according to Pluristem president and co-CEO Yaky Yanay. “We will be in an excellent position to enter the US market,” he noted.
“A great advantage of our product is that one doesn’t have to do prescreening to know what level of radiation the victim was exposed to. If a person hasn’t been exposed to any radiation, the body does not show stress signals and even if he gets the PLX-R18 injections, nothing will happen, unlike with other available products,” said Yanay. “In addition, our product – which has already proven itself effective on animals – has a three-year shelf life and can be stored at low temperatures. We are working to extend this to five years. When needed, the stem cells need only be defrosted and injected into the muscle.”
Since the product can be stored on site of possible radiation accidents or terror threats, it need only be restored to room temperature and administered immediately instead of the days needed to send over shipments.
Even without terror, radiation accidents do occur. There was the catastrophic Chernobyl nuclear reactor meltdown on April 26, 1986, in which a systems test caused a sudden and unexpected power surge, triggering havoc from a reactor vessel rupture and a series of steam explosions. The fallout drifted over large parts of the western Soviet Union and Europe, causing deaths and diseases, such as thyroid cancer, among large numbers of people immediately and even decades following the accident.
On March 11, 2011, a major earthquake and the resultant tsunami in Japan caused the cooling of the reactors and pools of used fuel at the Fukushima Daiichi nuclear plants. Large amounts of radioactive materials were released, and the effects continue even today.
There was no treatment option during either of these – or other – nuclear reactor accidents, but now there is PLX-R18 which, thanks to the Israeli developers, could save many lives in the future.