Innovative, breakthrough technology developed at the Hebrew University of Jerusalem (HUJI) has made possible the speedy development of drugs – including cancer medications – using bionic chips while eliminating the need for experiments on lab animals.
A new study led by Prof. Yaakov Nahmias, head of HUJI’s Center for Bioengineering and founder of the Tissue Dynamics company developed a His work with his research team has just been published in the prestigious journal Science Translational Medicine under the title “Mechanism and reversal of drug-induced nephrotoxicity on a chip.”
Tissue Dynamics Ltd. is a groundbreaking biotechnology company that develops drug toxicity and efficacy screening tools for the pharmaceutical and cosmetic industries. Its kinetic screening platform uses sensor-integrated organ on chip technology to monitor changes in metabolic function in real time; this minimizes false-positive and false- negative errors. The technology has led to the development of a new drug to prevent renal (kidney) failure in chemotherapy treatments on human tissues
Developing drugs and bringing them to market is a long process, full of obstacles and expensive. On average, the development of a single drug costs the pharmaceutical industry about $ 2.6 billion and takes about 12 years to bring to market. One of the major problems in the field, is the inability to observe drug behavior in humans from experiments in mice and rats. Lab animals have genetics and physiology that are different from humans, so drugs that are effective in mice repeatedly fail in clinical trials on humans.
Drug-induced toxicity to the kidneys causes over 1.5 million adverse events annually in the US alone, affecting about a fifth of the adult population. The incidence of drug-induced nephrotoxicity among the elderly may even be as high as 66% due to prescription medications related to diabetes and cardiovascular disease, the team wrote. Although renal impairment is often reversible, its management was estimated to cost about $3.5 billion annually.
The technology to replace animal experiments in human tissues began three decades ago, but although such systems are already on the market, it has not yet been proven that they can significantly shorten the path to drug development. Nahmias’s breakthrough was a combination of tiny sensors embedded in human tissue that make it possible to measure in real time the rate of metabolism in tissues such as liver, kidneys and heart. The accurate measurements allowed the HUJI team to obtain reliable information in real time on the mechanism of action of various drugs and chemicals in the kidneys.
Using the new technology, Nahmias and his doctoral student Aharon Cohen have discovered a new mechanism for the toxicity of one of the common drugs in chemotherapy – cisplatin – which causes kidney damage in more than a third of its patients. “Our system has shown that cisplatin interferes with the passage of sugar in the kidneys and therefore causes fat accumulation and damage. A quick scan showed that empagliflozin, a drug that prevents the absorption of sugar in the kidneys, prevents the damage and makes chemotherapy safer,” said Nahmias.
Cisplatin, a platinum-based drug, has been in use for over 40 years and is still considered one of the most commonly used chemotherapy drugs for patients with ovarian, stomach, lung, head, neck, bladder and testicular cancer. The kidney damage caused by the use of cisplatin limits its use to only a few days in any chemotherapy treatment.
Nahmias’s discovery led him to work with Tissue Dynamics, which has commercialized the technology for retrospective clinical research of 247 patients at Hadassah-University Medical Center in Jerusalem. This research confirmed the results of the HUJI study. “In fact, almost no kidney damage has been measured in cancer patients who have taken our drug combination,” declared Nahmias.
This is the first time that researchers have used chip-on-organ technology to develop a drug from a clinical trial without the use of lab animals. “This groundbreaking technology will not only shorten the time for essential drugs to reach the shelf, but also make unnecessary many of the experiments in the animals. This will save money, time and a lot of suffering in the animals,” he concluded.
Tissue Dynamics is continuing to develop innovative tools for drug development and is already advancing with the new cancer drug combination for clinical trials and regulatory approval.