Prof. Benjamin Sredni, Former Chief Scientist of Israel’s Ministry of Health, is Director of Bar-Ilan’s Cancer, Aids and Immunology Research (CAIR) Institute, senior member of the Mina and Everard Goodman Faculty of Life Sciences, and Dean of the School of Graduate Studies.
Sredni’s research is focused on regulation of the immune system by immunomodulators that shift immune responses from Th2 to Th1, and thus, are beneficial in various clinical conditions.
In his lab, the activities and mechanism of the AS101 immunomodulator synthesized by Prof. Michael Albeck were researched, and it was found to exert beneficial effects in the treatment of cancer as well as several autoimmune and neurodegenerative diseases such as Alzheimer’s, lupus and diabetes.
Research conducted in Sredni’s laboratory has shown that AS101 has radio- and chemo-protective effects on hemopoiesis in mice that have been irradiated or treated with various chemotherapeutic drugs. Apart from AS101’s ability to protect and reconstitute BM progenitor cells, the compound was shown to protect functional properties of BM stromal cells from toxic effects of DNA damaging agents.
These properties enable AS101 to be used in combination with cyto-reducing treatments for cancer.
AS101, currently undergoing Phase II clinical trials in combination with chemotherapy on cancer patients, demonstrates reduction of BM toxicity, expressed by decreased neutropenia and thrombocytopenia. These findings suggest that radio- and chemo-immunotherapy protocols with AS101 have considerable potential for clinical application in minimizing adverse cytotoxicity resulting from alkylating agents.
The major problem in the treatment of cancer is the fact that tumor cells become resistant to chemotherapy and acquire the capability to develop metastasis. Recent studies have shown that AS101 has the ability to change non-responding tumor cells to responsive ones, thus making chemotherapy treatment effective. Moreover, it also prevents the development of metastasis. This study is now in clinical trials with Acute Myeloid Leukemia patients.
In other studies, Sredni’s group has investigated changes in T-lymphocyte subsets and lymphokine secretion in Alzheimer’s disease (AD), and its correlation with disease stage and severity of dementia. They found that different cytokines seem to have different functions in dementia, which may account for increased levels of acute phase proteins in AD, and thus possibly play a role in AD pathogenesis.
Another area of study in Sredni’s lab is the changes in cytokine levels in Parkinson’s disease and their resulting influence on the development of the disease. AS101 was also found to have three additional activities that prevent neuronal death: it acts as an anti-inflammatory agent, increases neurotropic factors, and inhibits caspases, thus preventing apoptosis. Based on the re-sprouting of new neurons in Parkinsonian animal models as a result of these properties, clinical trials with Parkinson’s patients are planned.
AS101 has demonstrated immunomodulating activity in viral diseases such as West Nile Virus (WNV), CMV, and more recently in Avian and Swine Flu, as well as in parasitic diseases such as Babesiosis and Leshmania.
Sredni and his team aim to investigate and clarify the mechanism of action of AS101 as a radio- and chemoprotective drug. Specifically, they intend to evaluate the effect of AS101 on the abundance of CD34 positive pluripotent stem cells. Additionally, they will explore its role in the regulation of adhesion receptors of the integrin family and their ligands on enriched stem cells and BM stromal cells.
They also plan to characterize immunological and neurological parameters of lymphocytes from Alzheimer patients as correlated with progression of the disease. Sredni’s laboratory team is currently conducting studies on autoimmune diseases such as Lupus, Multiple Sclerosis, Crohn’s Disease and Psoriasis.