From the bench to the bedside

New TAU Translational Medicine Center aims to develop pharmaceuticals better, faster and for less money

A scientist prepares protein samples for analysis in a lab at the Institute of Cancer Research in Sutton (photo credit: REUTERS)
A scientist prepares protein samples for analysis in a lab at the Institute of Cancer Research in Sutton
(photo credit: REUTERS)
When Prof. Rina Rosin-Arbesfeld, an associate professor in the Department of Clinical Microbiology and Immunology at Tel Aviv University, had an idea for how to treat a genetic predisposition to colorectal cancer patients using the already existing antibiotic erythromycin, she reached out to a colleague at Tel Aviv Sourasky Medical Center – Ichilov Hospital. Together, she and Dr. Revital Kariv ran a clinical trial.
Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide. Many patients who ultimately develop cancer start getting polyps at an early age. Reducing the number and size of these polyps can reduce their likelihood to develop cancer and the cancer’s severity, explained Rosin-Arbesfeld.
The results?
“In terms of overall effect, in most patients, polyp burden was reduced after treatment and that tendency was maintained even eight months post-treatment,” said Rosin-Arbesfeld. “Since the patients that were recruited to the trial were already under observation, we were able to compare the annual change of polyp measurements in the year that preceded erythromycin treatment and the year following treatment.”
She added, “We have very good results.”
They will continue to follow up on these patients.
Now, Rosin-Arbesfeld and Kariv are collaborating in recruiting additional patients and trying to see if they can modify and improve the drug. This is just one example of preliminary stages of the newly launched TAU Translational Medicine Initiative, an effort to leverage Israeli academia to bridge the pharmaceutical drug innovation gap – whereby exciting discoveries made in the lab too often do not make it to the next stage of drug development – and expand the arsenal of drugs available to doctors in Israel and around the world.
“Translational medicine is when what we find in the lab can be brought to the clinic – from the bench to the bedside,” said Dr. Dinorah Friedmann-Morvinski, a member of the Department of Biochemistry and Molecular Biology at TAU.
The new program is aimed at translating original disease research into pioneering drugs and therapies that could ease suffering and save lives, said Prof. Dan Peer, who is heading the new Center, the first of its kind in Israel.
The Translational Medicine Center is modeled after a revolutionary approach to drug research first adopted by universities such as Harvard, Stanford and New York University. It replaces the traditional drug development model whereby only pharma/VC companies pay for the proof-of-concept and early clinical trials of drug candidates.
The center includes education, mentorship, and funding for promising product proposals. Post graduate-level courses about the drug discovery and development process are offered. Since drug development is a repetitive process that requires specialized knowledge and technical proficiency in several areas, the Translational Medicine Initiative will also offer mentoring to assist in this process, including weekly seminars with industry and academic experts.
Peer said TAU put out a call for new proposals in April and already more than 60 applications have been received, many of which look promising. The goal is to have 10 translational medicine projects running in parallel in year one and another 10 in year two. After that, the center will reevaluate and raise more funds.
“We are super optimistic,” Peer said. “This is really exciting for us.”
And it could have global impact. Peer explained that despite the more than 10,000 known human diseases, only 500 FDA-approved families of drugs are available to doctors. Moreover, an average of only 25 to 30 new drugs are approved every year.
Peer said there are two reasons for this: the slowing pace of innovation in the global pharma industry and the innovation gap in academia, whereby exciting discoveries made in the lab too often do not make it to the next stage of drug development.
Israel is uniquely positioned to close these gaps. To date, according to the university, more than 20% of all FDA-approved drugs have been generated from scientific research conducted by Israeli universities.
TAU SPECIFICALLY works with 17 major hospitals. Peer believes TAU researchers are poised to identify potential “golden eggs” at TAU’s biomedical research labs, which could then be translated into viable treatment candidates. Additionally, just as Arbesfeld and Kariv did with erythromycin, he said researchers could discover ways to repurpose existing drugs for the treatment of other diseases, which also requires clinical exploration to prove efficacy.
TAU scientists have already made headway in the development of novel drugs and therapies for cancer, inflammatory bowel diseases, Alzheimer’s, ALS, rare genetic diseases and other illnesses. Their work is boosted by the facilities and expertise at TAU’s Blavatnik Center for Drug Discovery, a suite of laboratories that integrates biology, chemistry and computer science to advance therapeutic leads.
Friedmann-Morvinski is working on designing novel therapeutic approaches to glioblastoma, combining adoptive immune gene therapy and nanotechnology. Glioblastoma are tumors that arise from astrocytes – the star-shaped cells that make up the “glue-like,” or supportive tissue of the brain. These tumors are usually highly cancerous, because the cells reproduce quickly, and they are supported by a large network of blood vessels.
“There has been tremendous success in recent years in treating cancer patients with their own immune cells,” Friedmann-Morvinski explained. “What you do, is you take the patient’s white blood cells, engineer them, and reintroduce them back into the body with a new receptor that helps these cells recognize the tumor and how to kill it. But the success has been with liquid tumors. We are trying to bring that kind of therapy to solid tumors.”
She said the nanotechnology is being used to try to test different drugs and other ways to target and kill cancer cells.
“Eventually, these two approaches will merge into the same goal: a new way to treat people with glioblastoma,” Friedmann-Morvinski said.
She noted that collaboration with doctors in a hospital setting is essential because academicians cannot do clinical trials on their own. By working with a hospital, and ideally through the Translational Medicine Initiative, researchers will have more funds and better mentorship to take their research from the bench to the bedside.
Peer has experience with this, too. Several years ago, he and colleagues at the department of cell research and immunology showed that Prozac, commonly known for treating depression, also dramatically enhances the effectiveness of a widely used anti-cancer drug doxorubicin.
Together, they reformulated Prozac into an anti-cancer drug (given together with chemotherapy) as a blocker of cancer multi-drug resistance cells and it is now approved for use in the treatment of pancreatic cancer and a specific brain tumor, medulloblastoma.
“Prozac is a very interesting non-specific blocker of cancer resistance,” said Peer.
In their laboratory experiments, TAU scientists Dr. Mirit Argov, Peer and Prof. Rimona Margalit found that Prozac enhanced doxorubicin’s efficacy more than 1,000%. Prozac, in effect, worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it. In a subsequent clinical study and working with a major drug developer, the team validated Prozac’s potential, enabling it to be used with chemotherapeutic drugs to curb drug resistance.
“We feel we are giving back to society,” said Peer. “We can take good ideas and turn them into excellent ideas and move those excellent ideas from the lab into the clinic. My goal is to push as much as we can.”