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INVENTIONS FOR LICENSE

MCL 2256.0 and 3104.0: Blood Test for Diagnosis and Prognosis of Bipolar Disorder

Christine Konradi, Ph.D., et al.

Summary

This invention provides a simple, easy to carry out, method to determine if an individual is suffering from, or is at risk of developing bipolar disorder; or of distinguishing bipolar disorder from other psychiatric illnesses. The method involves a simple blood test which could be carried out in any doctor's office or hospital, and which can be commercialized either as a kit or as a mail-in reference service. Because there are currently no recognized laboratory or clinical tests for bipolar disorder, this test could greatly improve the ability to diagnose this disorder earlier and more definitively than is now possible.

Background and Market Needs

Bipolar disorder is a mood disorder characterized by pathological mood swings from mania to depression, which affects approximately 5.7 million American adults, and which has been estimated to be responsible for a national annual economic burden in the U.S. of over $40 billion, including $14 billion annually in lost workplace productivity. The U.S. market for treatment of bipolar disease was estimated at about $2 billion in 2004 and $2.4 billion in 2007, while the world market has been projected to reach as much as $6.6 billion by 2011.

Bipolar disorder is typically diagnosed based on the basis of symptoms and family history, for example, by using instruments such as the Mood Disorder Questionnaire (MDQ) to assess symptoms against the clinical definition of the disorder in the DSM-IV. However, no clinical or laboratory tests exist to verify the diagnosis, and it is often hard for psychiatrists to distinguish bipolar disorder from other illnesses such as schizophrenia. An accurate, reliable diagnostic test would be invaluable in facilitating early diagnosis of the disorder, and allowing psychiatrists to differentiate between bipolar disorder and other psychiatric disorders.

Description

Although bipolar disorder appears to be heritable, no single genetic locus has been repeatedly linked to this condition, and the mechanisms underlying the disorder remain unknown. In the inventors' previous research, the regulation of 13,000 genes in brain tissue from patients with bipolar disorder was examined, and numerous changes in expression levels of genes were found in the brains of subjects suffering from bipolar disorder compared to control subjects (McLean invention reference MCL 2256.0). The greatest differences were seen in genes whose expression products involve mitochondrial function or energy utilization. In more recent research, the inventors found that differential expression of certain of these genes can also be seen in lymphocytes of bipolar subjects compared to controls, when the lymphocytes are treated ex vivo in a certain manner. Specifically, lymphocytes of normal controls responded to glucose deprivation with an up-regulation of nuclear transcripts for proteins of the electron transfer chain, whereas subjects with bipolar disorder had a tendency to down-regulate these transcripts (McLean invention reference MCL 3104.0).
MCL 2256.0 and 3104.0 Real-time quantitative polymerase chain reaction analysis for low glucose for bipolar disorder (BPD) lymphocytes (n=16) vs normal control (NC) lymphocytes (n=15). Four genes were used in the quantitative PCR verification. *P =0.05. †P=0.01. From Naydenov, et al. 2007 PMID 17485607.

Potential Commercial Uses

By enabling circulating cells to be used in this assay, the new research enables a simple, rapid blood test that can be used to diagnose bipolar disorder. The invention features a diagnostic method for detecting the presence of, or propensity for, bipoloar disorder in a patient by detecting specific patterns of gene expression in lymphocytes subjected to a specific ex vivo treatment. The test is simple and easy to carry out, in that it can be conducted using easily-obtainable blood samples from patients, using standard methods of measuring gene expression. The test provides a quick diagnosis of whether the patient has a genotype which puts him or her at risk of developing psychotic disorders such as bipolar disorder.

Publication and Patent Status

McLean Hospital is the owner of pending U.S patent applications claiming this invention. The research underlying the invention has been published as Konradi et al. (2004) Arch. Gen. Psychiatry 61:300-308 PMID 14993118 and Naydenov, et al. (2007) Arch Gen Psychiatry 64:555-564 PMID 17485607.

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
dglass@mclean.harvard.edu