Maxim Announces Results of Preclinical Research Suggesting Ceplene Accelerates Recovery in Liver Damage Model
Monday November 4, 3:00 am ET
SAN DIEGO--(BUSINESS WIRE)--Nov. 4, 2002--Maxim Pharmaceuticals, Inc. (Nasdaq: MAXM - News; SSE: MAXM) today announced the results from preclinical studies suggesting that Ceplene(TM) (histamine dihydrochloride) accelerated recovery from alcohol-induced liver damage in an animal model of alcoholic liver disease (ALD). In the study, animals treated with Ceplene recovered from alcohol-induced liver injury more rapidly than the untreated control animals.
In the United States alone, approximately 25 million people -- one in every ten -- have been afflicted with chronic liver, bile duct or gallbladder diseases. More specifically, liver cirrhosis resulting from alcohol abuse is one of the ten leading causes of death in the United States. Earlier this year the Company presented the results of the first studies suggesting that Ceplene may protect against alcohol-induced liver injury in an animal model.
In the study reported today, liver injury was induced through the administration of a single dose of ethanol once per day for four weeks in rats. After four weeks, alcohol administration was discontinued and animals were treated with either histamine (0.5 mg/kg) or a vehicle control by subcutaneous injection twice a day for one week. Liver damage was assessed through measurement of the liver enzymes ALT and AST, markers that are elevated when there is damage to the liver. Animals that were treated with histamine achieved normalization of ALT and AST levels in approximately one-half of the time experienced by the control animals. The results are described by Hornyak, Little, Radi, Gehlsen and Haaparanta in "Histamine Accelerates Recovery Time of Early Alcohol-induced Liver Injury in the Intragastric Gavage Rat Model" (American Association for the Study of Liver Diseases).
A second alcohol-damage study demonstrated that histamine treatment also prevented the decrease of IL-1 receptor antagonist (IL-1Ra) mRNA levels, maintaining normal levels of this anti-inflammatory cytokine that blocks the pro-inflammatory IL-1 cytokine family. Histamine also increased the sustained mRNA levels of interferon-gamma, a cytokine known to promote T cell and Natural Killer cell proliferation and thought to be a direct inhibitor of viral hepatitis replication. Based on these results, the researchers concluded that histamine's combined effect of reducing oxidative stress and balancing the cytokine profile during a diseased condition may help accelerate healing of the liver while promoting the recovery of key immune cells in the liver. In addition, the finding that histamine can increase the levels of interferon-gamma may be one of the mechanisms contributing to the benefits observed in clinical studies of Ceplene combination therapy for the treatment of hepatitis C.
"The active agent in Ceplene reduces oxidative stress as well as modulating several key cytokines like TNF-alpha, IL-12, IL-18 and IFN-gamma, each of which have been shown to be involved in regulating the severity of liver disease," said Dr. Kurt Gehlsen, Maxim's Chief Scientific Officer. "These results suggest that we should consider investigating the protective mechanism of Ceplene as a potential therapy for certain non-viral chronic liver diseases such as nonalcoholic steatohepatitis (NASH) and ALD."
Ceplene and Maxim Overview
Research has shown that oxygen free radicals released by certain immune cells can suppress the immune system and damage normal tissue, a process commonly referred to as oxidative stress. Oxidative stress, implicated in numerous diseases, is most pronounced in the liver and can damage or destroy liver tissue in patients with hepatitis and other chronic liver diseases.
Ceplene, based on the naturally occurring molecule histamine, has been shown in preclinical work to prevent the production and release of oxygen free radicals, thereby reducing oxidative stress. Accordingly, treatment with Ceplene has the potential to prevent or reverse damage induced by oxidative stress, thereby protecting critical cells and tissues, including the liver. |
