|Sarah Ferber, Ph.D.|
By Joseph Sherman
An Israeli team is developing a new method for treating Diabetes.
About 285 million people are living with diabetes worldwide. Several kinds of treatment options exist, but all of them have drawbacks. For example, insulin therapy can trigger everything from weight gain to hypoglycemia, and its administration must be constantly controlled and monitored by the patient.
But what if a diabetic patient’s own cells—extracted from mature tissue—could be turned into insulin-producing machines, secreting insulin automatically when needed? According to a biotech company named Orgenesis, this kind of cell therapy, known as autologous cell replacement, holds very real potential.
Orgenesis’s efforts have been inspired by the pioneering research of Sarah Ferber, Ph.D., who is Director of Molecular Endocrinology at Sheba Medical Center in Tel Hashomer, Israel, and Chief Scientific Officer at Orgenesis.
In the treatment being developed by Dr. Ferber and Orgenesis, a standard liver biopsy is taken from the patient in a clinical center and sent to a laboratory. In the lab, the liver cells are treated with a special technique.
At the clinical center, the newly formed cells are then transplanted back to the patient’s liver where they secrete insulin. Since the initial liver cells were taken from the patient himself or herself, the chance of rejection is very limited. Orgenesis has successfully tested its technology in preclinical studies, and is working toward initiating clinical trials in humans.
Orgenesis CEO Jacob BenArie explains, “We plan to enter into a formal review from the U.S. Food and Drug Administration and The European Medical Association, which is a key step in the development process for the company.”
Dr. Ferber earned her PhD under Nobel laureates Aaron Ciechanover and Avram Hershko at the Technion in Haifa. She moved from pure biochemistry to diabetes research through a fellowship at Harvard Medical School in the U.S.
BenArie notes, “Dr. Ferber is a pioneer and a trailblazer in this area. At first her ideas were not embraced by people in the scientific community, and at times met with controversy. Today, her ideas are widely accepted by her peers.”
One of the major challenges for a small company like Orgenesis, says BenArie, is to find the right partners and key opinion leaders who believe in the company’s mission and technology, and to make them part of the company’s team. “This requires a new kind of skill where one has to think outside the box and work just a little harder for funding,” he notes.
BenArie continues, “In Israel, we don’t have the advantage of possessing bountiful natural resources such as metals, oil or gas. As a result, we focus mainly on technology and science. Israeli companies continue to lead in developing cell-based therapeutic products. We’re proud to be working in this space, and we hope to distinguish ourselves as development of our treatment continues.”
Dr. Sarah Ferber is the head of the Endocrine Research Unit at the Sheba Medical Center.
She graduated in biochemistry at the Technion under the supervision of Professor Avram Hershko and Professor Aharon Ciechanover, winners of the Nobel Prize in Chemistry in 2004. She completed a post-doctoral fellowship at the Joslin Diabetes Lab at Harvard Medical School.
The research in the Ferber's group focuses on tissue engineering, adult cells reprogramming and cell replacement therapy for diabetes. The research is based on the assumption that developmental factors that control pancreas organogenesis in the embryo can be implemented in redirecting the developmental fate of other adult tissues towards the pancreatic lineage and function. The capacity to activate the pancreatic lineage and function in adult liver cells, suggest that we carry our own 'stem-like-cells throughout adulthood, thus obviating the need for embryonic stem cells for generating organs in need.
The lab has established a pioneer therapeutic approach based on converting adult liver tissue into functional glucose regulated insulin producing cells. The promising results in in-vitro studies using human liver tissues and in mice in-vivo model, were published in important scientific papers.
The proof of concept studies demonstrated that adult human liver cells retain substantial plasticity and can be induced to assume new fates and function, upon appropriate molecular manipulation. As such liver has become a pancreatic progenitor tissue that can be used for autologous cell replacement therapy for diabetic patients.
Methods used in the lab: The developmental redirection process is analyzed at molecular, cellular and functional levels.
Some of the methods include: primary culture of adult tissues, gene delivery using recombinant adenoviruses, lineage tracing using Lenti-viruses, Global analyses of alterations in the profile of gene expression by micro-array-chip analyses, physiological studies using mice models.