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עמוד בית
Thu, 21.11.24

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March 2019
October 2014
Rina Aharoni PhD and Ruth Arnon PhD

A fundamental challenge for multiple sclerosis (MS) therapy is to promote repair and remyelination beyond their limited spontaneous extent. Glatiramer acetate (GA, Copaxone®), an approved treatment for MS, has been shown to induce immunomodulation as well as neuroprotection in the inflamed central nervous system (CNS) in MS and in its model, experimental autoimmune encephalomyelitis (EAE). Using electron microscopy, immunohistochemistry, and advanced magnetic resonance imaging, we have demonstrated diminished myelin damage in GA-treated mice, in both relapsing-remitting and chronic EAE, even when treatment was applied late after the disease exacerbation, suggesting repair. Furthermore, quantitative analysis indicated significant elevation in remyelinated axons in GA-treated compared to untreated EAE mice. To further prove that GA can promote myelination, we studied its effect in the developing naïve CNS, when injected postnatally. Immunohistochemical and ultrastructural analyses revealed significant increase in the number of myelinated axons, the thickness of the myelin encircling them, and the resulting g-ratios in the spinal cords of GA-injected mice compared to their phosphate-buffered saline-injected littermates. A prominent elevation in the amount of progenitor oligodendrocytes and their proliferation, as well as in mature oligodendrocytes, implied that the effect of GA is linked to the differentiation along the oligodendroglial cascade. Furthermore, a functional advantage in rotating rod test was exhibited by GA-injected mice over their littermates. These cumulative findings indicate that GA treatment affects myelination under inflammatory as well as non-inflammatory conditions, supporting the notion that the repair process in the CNS can be up-regulated by therapy.

November 2006
R.R. Leker, R. Eichel, G. Rafaeli and T. Ben-Hur
 Acute ischemic stroke is one of the leading causes of mortality and chronic disability in the western world. Yet, despite the enormous socioeconomic burden that it imposes, therapies to combat AIS are not widely available. Moreover, revascularization of the ischemic tissue with tissue plasminogen activator, the only FDA-approved therapy for AIS[1], is hampered by a very narrow therapeutic time window and is only used in a minority of patients. Cerebral ischemia leads to brain damage caused by several pathologic mechanisms that can potentially be blocked by neuroprotective drugs that aim to salvage the ischemic penumbra. However, despite numerous clinical trials no single drug candidate has proved efficacious in AIS. The current situation clearly calls for novel therapeutic strategies to be used in acute ischemic stroke. This review surveys some of these novel and promising cutting edge therapies.







[1] AIS = acute ischemic stroke


October 2006
H.S. Oster, M. Hoffman, S. Prutchi-Sagiv, O. Katz, D. Neumann and M. Mittelman
 Recombinant human erythropoietin has become an essential part of the management of anemic patients with end-stage renal disease. It is also used to treat the anemia associated with cancer and other diseases, and it improves quality of life. In recent years, studies in animals and humans have focused on the use of rHuEPO[1] for other indications. It has been found to play a role in both cardioprotection and neuroprotection. It has effects on the immune system, and can cause regression in hematologic diseases such as multiple myeloma. It may also improve the response of solid tumors to chemotherapy and radiation therapy. On the other hand, concerns have been raised following two studies of patients with solid tumors in whom those treated with rHuEPO had diminished survival. Criticism of the design of these studies makes it clear that large, well-designed, randomized trials must be performed to determine the role of rHuEPO in the treatment of cancer, and more generally to clarify the full clinical benefits of the drug, while minimizing the harm.







[1] rHuEPO = recombinant human erythropoietin


August 2003
R. Djaldetti, N. Lev and E. Melamed

Progressive neurodegenerative disorders share common mechanisms of cell death, and in all likelihood multiple factors are involved in every disease. Therefore, several neuroprotective agents are being investigated with the purpose of slowing or preventing further deterioration of cell loss. These include experimental animal and clinical studies on the neuroprotective effects of caspase inhibitors, antioxitands, glutamate antagonists, anti-inflammatory agents and trophic factors in several neurodegenerative diseases. At present there is limited clinical evidence for direct neuroprotective effects against these diseases, but much effort is being invested in research on novel technologies and compounds.

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