Fgf2-related methods for diagnosing and treating depression

a depression and fgf2 technology, applied in the field of fgf2related methods for diagnosing and treating depression, can solve the problems of ineffective and reliable diagnosis and rate, lack of biomarkers, and difficulty in diagnosing bipolar disorder, and achieve the effect of accurate diagnosis of mental illness

Inactive Publication Date: 2009-09-17
PRTZKER NEUROPSYCHIATRIC RES FUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]The present invention provides novel assays for the diagnosis and detection of various mental illnesses. The assays, which include assays for detecting the level of expression of various genes associated with mental disorders, allow the practitioner to obtain a more accurate diagnosis of mental illness in a subject, and allow the practitioner to distinguish between various mental illnesses and associated pathologies. The invention also provides compositions useful for practicing the methods of invention, and for developing further diagnostic methodologies, as well as new therapeutics, to aid in the treatment of mental illness.

Problems solved by technology

Clinical depression, including both bipolar disorders and major depression disorders, is a major public health problem, affecting an estimated 9.5% of the adult population of the United States each year.
The current lack of biomarkers and the ineffectiveness and reliability of the diagnosis and rates are important issues for the treatment of mental disorders.
Diagnosing bipolar disorder is difficult when, as sometimes occurs, the patient presents only symptoms of depression to the clinician.
The consequences of such misdiagnosis include a delay in being introduced to efficacious treatment with mood stabilizers and a delay in seeking or obtaining counseling specific to bipolar disorder.
Also treatment with antidepressants alone induces rapid cycling, switching to manic or mixed state, and consequently increases the risk of suicide.
Furthermore, in addition to a lack of efficacy, long onset of action and side effects (sexual, sleep, weight gain, etc.), there are recent concerns relating to the undesirable effects of antidepressants on metabolic syndromes, such as diabetes and hypercholesteremia.

Method used

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  • Fgf2-related methods for diagnosing and treating depression
  • Fgf2-related methods for diagnosing and treating depression
  • Fgf2-related methods for diagnosing and treating depression

Examples

Experimental program
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example 1

Differential Expression of Genes Associated with Suicide in Both BP and MDD Subjects

[0257]Previous studies have investigated genes associated with mood disorders and suicidal tendencies, using microarrays and PCRs to analzye gene expression (Sibille et al>, 2004; Yanagi M, et al., J Hum Genet., 50(4):210-6 (2005)). Neither investigation, however, used a stringent analysis of suicide compared to mood disorder and suicide compared to controls to detect genes that might be most representative of suicide. This Example describes microarray gene expression profiles in the amygdala, anterior cingulate, and cerebellum in postmortem brains from BPD and MDD patients that committed suicide, focusing on mRNA expression levels of the molecules which regulate white-matter, oligodendrocyte, myelin, and other pathways. The genes identified here may be used as biomarkers for detecting and treating suicidal behavior.

[0258]Genes were discovered by selecting subjects run on U133P chips with mRNA qualit...

example 2

Identification of Lithium Responsive Genes which are Dysregulated in BPD

[0261]This Example demonstrates that certain genes in non-human primates (healthy rhesus macaque monkey) are differentially expressed in response to treatment with the mood-stabilizing drug, lithium (Li), the drug of choice for the treatment of BP. Gene expression profiling was carried out on the anterior cingulate cortex (AnCg), dorsolateral prefrontal cortex (DLPFC), hippocampus (HC) and amygdala (AMY) of rhesus macaque monkeys, using the gene expression detection methods described herein, and compared to the human postmortem results described above. Table 2A shows the lithium-responsive genes which had been previously identified in the literature and which were confirmed by the present investigation. Table 2B shows genes that are newly identified as lithium-responsive in primates and which are also dysregulated in human subjects with bipolar disorder.

example 3

FGFR2 Variant Differences in Mood Disorders

[0262]The FGF receptor 2 (FGFR2) transcript is consistently found to be decreased in several brain areas of depressed subjects (see, e.g., U.S. patent application Ser. No. 10 / 701,263, filed Nov. 3, 2003, published as U.S. Pat. Publ. No. 20040152111-A1 on Aug. 5, 2004). The human FGFR2 gene contains 19 exons and produces as many as 13 splice variants. These variants fall into three main functional classes: first, variants that lack the transmembrane and tyrosine kinase domain which are thought to be soluble receptors; second, variants that contain the Ig IIIc type domain encoded by exon 9; and third, variants that contain the Ig IIIb type domain encoded by exon 8. The Ig III type domain confers ligand specificity and thus these latter two variants have different pharmacological profiles based on their use of the IIIc or IIIb domain. This Example describes PCR-based measurements of exons present in total RNA derived from human cortex (dorsola...

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Abstract

The present application relates to the treatment and diagnosis of mood disorders, including bipolar disorder, major depression disorder and schizophrenia. The invention provides novel diagnostic markers and assays, as well as research tools for the development and discovery of agents and compounds which are useful for treating patients who suffer from mental illness.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60 / 736,526, filed Nov. 12, 2005, and U.S. Provisional Patent Application Ser. No. 60 / 829,516, filed Oct. 13, 2006.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT[0002]Certain embodiments of the invention described herein were developed with the support of the United States government (Conte Center grant (NIMH) L99 MH60398). Accordingly, the U.S. government may have rights to certain embodiments of the invention.BACKGROUND OF THE INVENTION[0003]Clinical depression, including both bipolar disorders and major depression disorders, is a major public health problem, affecting an estimated 9.5% of the adult population of the United States each year. While it has been hypothesized that mental illness, including mood disorders such as major depression (“MDD”) and bipolar disorder (“BP”) as well as psychotic disorders s...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00C12Q1/68
CPCA61K38/1825C12Q1/6883G01N33/5023C12Q2600/106C12Q2600/136C12Q2600/158G01N2800/304A61P25/18A61P25/22A61P25/24A61P25/30A61P43/00A61K38/03A61K38/10A61K38/1774
Inventor AKIL, HUDAWATSON, STANLEY J.EVANS, SIMON J.TURNER, CORTNEYBERNARD, RENEKERMAN, ILANTHOMPSON, ROBERT C.BURMEISTER, MARGITSCOTT, LAURA J.MENG, FANBOEHNKE, MICHAELBUNNEY, JR., WILLIAM E.VAWTER, MARQUIS P.JONES, EDWARD G.CHOUDARY, PRABHAKARA V.MYERS, RICHARD M.SCHATZBERG, ALAN F.LI, JUNABSHER, DEVINTOMITA, HIROAKI
Owner PRTZKER NEUROPSYCHIATRIC RES FUND
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