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MCL 3088.0: Methods for Treatment of Mood Disorders

Bruce Cohen, M.D., Ph.D., Beth Murphy, M.D., Ph.D.

Background and Description

This invention offers a potentially powerful new approach to the treatment of mood disorders, that can be practiced with at least one known compound with a favorable human safety profile. Animal and human studies suggest that modulation of the kappa opioid receptor (KOR) can alter mood: direct activation of KOR causes depressogenic effects, while blockade of KOR has antidepressant-like effects. Consistent with this, the effects of current antipsychotic drugs, which are potent antimanic agents, may be mediated in part,through an increase in the activity of dynorphinergic neurons, resulting in the release of dynorphin, the endogenous agonist at KOR. Based on the above evidence, the inventors have theorized that directly-acting kappa agonists might ameliorate the symptoms of mania. The inventors have found that an existing analgesic agent, known to be a partial KOR agonist, caused a statistically significant reduction in manic symptoms in a small open-label clinical study. Ten subjects, all diagnosed with bipolar mania, received two doses of this compound, two hours apart, and were assessed over a 6-hour period using the Mania Acute Change Scale (MACS). In the first hour after each dose, the average MACS score decreased 41-44%. Measured over the subsequent 3 days using a different rating scale, a statistically significant improvement in mood was also seen.

Potential Commercial Uses

The invention comprises methods of treating mania, bipolar disorder, or mood disorders by administering a kappa receptor agonist or partial agonist. The invention can be practiced using one specific commercially-available drug with a known human safety profile. This compound exists as a racemic mixture, and using the pure enantiomer could lead to an improved therapeutic outcome with a novel chemical entity.

Publication and Patent Status

McLean Hospital is the owner of an allowed U.S. patent application claiming this invention, which is expected to issue first quarter 2011.

Licenses Available

McLean Hospital is offering a worldwide exclusive license to this technology.

For more information, please contact:

David J. Glass, Ph.D.
Senior Associate Director, Technology Transfer
McLean Hospital Research Administration
115 Mill Street
Belmont, MA 02478-9106
(617) 855-3825 - tel
(617) 855-3745 - fax