Alcoholism can be characterized by a physical dependence of alcohol in addition to a variety of physical and mental deficiencies resulting from excess alcohol consumption, including cirrhosis, epilepsy, dementia, and depression. Physiologically, alcohol has been known to disrupt the normal function of cell membranes, although the associated mechanism is unclear. In the presence of ethanol, the enzyme phospholipase D (PLD) produces complexes harmful to neural cell membranes. This technology is a method to use PLD activity as a pharmacological target for medications aimed at treating alcoholism and alcohol-related disorders. Treatment of alcoholic patients with PLD inhibitors may reduce the toxic effects on the nervous system induced by ethanol.
Most current medications for alcohol disorders aim to decrease a person’s desire for alcohol and do not directly address the physiologic toxicity of alcohol. In normal physiology, PLD is the enzyme responsible for the production of the signal molecule phosphatidic acid and the regulation of many cell membrane processes. However, in the presence of excess ethanol, PLD preferentially produces phosphotidylethanol (PEtOH), which accumulates in neural tissues and can disrupt cell membrane function and signal mechanisms. Methods to reduce the activity of PLD, and thus PEtOH, may be used to mitigate the damage to neural cell membranes and improve symptoms of excess alcohol consumption.
PLD-knockout mice have been shown to have decreased levels of PEtOH and exhibit less motor dysfunction following alcohol intoxication.
Patent Pending (US 20120302604)
Tech Ventures Reference: IR 2609