Title:  Treatment of and/or prophylaxis against brain and spinal cord injury

United States Patent:  6,432,434

Issued:  August 13, 2002

Inventors:  Meyerhoff; James L. (Silver Spring, MD); Long; Joseph (Clarksville, MD); Koenig; Michael (Silver Spring, MD)

Assignee:  The United States of America as represented by the Secretary of the Army (Washington, DC)

Appl. No.:  556954

Filed:  April 21, 2000

The administration of .alpha.-lipoic acid (.alpha.LA) and dihydrolipoic acid (DHL) both as a preventive measure before exposure to conditions which may cause damage, such as rapid changes in atmospheric pressure, and as a means of preventing or ameliorating damage arising from such injury provides benefits not currently available. The active agents may be administered systemically or to the injured tissue. For example, when there is spinal cord injury, the active agents may be administered intrathecally.

DETAILED DESCRIPTION OF THE INVENTION

There are many instances when an injury may not be immediately life-threatening, but may have potential to cause severe disability. Injuries such as those arising from penetrating injuries, exposure to blast, blunt trauma, falls and vehicular accidents as well as spinal cord and brain injury secondary to systemic phenomena such as decompression sickness are examples of instances when use of .alpha.LA and dihydrolipoic acid in accord with the teachings of this disclosure would be appropriate. Conditions such as herniated discs or degenerative diseases such as amyotrophic lateral sclerosis and multiple sclerosis are pathological processes whose deleterious effects may be ameliorated by practice of the methods of the invention.

One great advantage associated with the use of .alpha.LA is that it may be administered orally, is readily absorbed and is converted to the more potent neuroprotectant, dihydrolipoic acid. It is well tolerated in man and may be given prophylactically to soldiers at risk for spinal cord injury.

The use of .alpha.-lipoic acid can be demonstrated for efficacy in preventing spinal cord injury using the following models: (1) Dynorphin-A induced ischemia, (2) animal models of spinal cord injury secondary to decompression sickness and (3) weight-drop models of spinal cord injury.

Since decompression sickness-induced spinal cord injury can be modelled by placing rats in a hyperbaric chamber, it is possible to use such a model to screen for clinically-available compounds which might mitigate risk in a vulnerable population. However, a model of spinal injury with less variability and higher throughput provides a more efficient way to test therapeutic concepts. The methods of the invention include prophylaxing against damage arising from spinal cord injury or pathology comprising administration of a neuronal protective amount of at least one agent chosen from among dihydrolipoic acid, .alpha.-lipoic acid or an ester of .alpha.-lipoic acid before exposure to circumstances which give rise to spinal cord injury. If damage has occurred, it is appropriate to treat the vertebrate who has incurred spinal cord or brain injury or pathology to prevent neuronal damage arising from said injury or pathology by administering a neuronal damage preventing effective amount of at least one agent chosen from among dihydrolipoic acid, .alpha.-lipoic acid or an ester of .alpha.-lipoic acid.

Claim 1 of 10 Claims

What we claim is:

1. A method of treating a vertebrate who has incurred spinal cord or brain injury due to trauma or changes in atmospheric pressure to prevent neuronal damage arising from said injury or pathology comprising administering to said vertebrate a neuronal damage-preventing effective amount of at least one active agent selected from the group consisting of dihydrolipoic acid, .alpha.-lipoic acid or an ester of .alpha.-lipoic acid to the vertebrate who is suffering from injury or pathology of the spinal cord or brain.
 

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