Columbia Technology Ventures

Inhibition of phospholipase D to treat acute and chronic effects of alcohol

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.

Limiting alcohol-related damage towards neural cells and motor dysfunctions via pharmacological inhibition of phospholipase D activity

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.

Lead Inventor:

Gilbert Di Paolo, Ph.D.

Applications:

  • Clinical treatment of physical and/or behavioral disorders associated with alcohol.
  • Limiting the toxic effect of alcohol on cells and/or tissues in research applications.
  • Measuring PLD activity using an administration of ethanol and mass spectrometry.

Advantages:

  • Directly treats the toxic effects of alcohol on the nervous system.
  • Treats tissues in the central nervous system, which can have secondary effects on a wide variety of other systems (e.g. musculoskeletal, cardiovascular, endocrine).
  • Can be used in non-compliant patients who have difficulty in reducing alcohol consumption.
  • Treats both acute and chronic effects of alcohol.
  • Allows for a gradual cessation of alcohol consumption.
  • Potential to improve care in the ambulatory setting in patients who overdose.

Patent information:

Patent Pending (US 20120302604)

Tech Ventures Reference: IR 2609

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