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NIMH Researchers ID Genes in Celexa Response


Depression patients with variations in two genes — GRIK4 and HTR2A — are more likely to respond to the medication citalopram (Forest’s Celexa) than are people without the variations, a study by the National Institute of Mental Health has found.

“The increased likelihood was small, but when people had both [the GRIK4] variation and one in a different gene [HTR2A] shown to have a similarly small effect in an earlier study, [patients] were 23 percent more likely to respond to citalopram than were people with neither variation,” NIMH says.

Gonzalo Laje, a clinical research fellow working in the Genetic Basis of Mood and Anxiety Disorders program at NIMH, says that the research is perhaps too early to determine whether a diagnostic may result. However, “I think we are on the right track and this is a good step forward,” Laje says.

Prior to developing a diagnostic, the researchers will have to perform whole-genome studies and analyze other genetic variations and predictors of outcome, such as copy number variations, other polymorphisms, and epigenetics. “We are still a ways away from having antidepressant diagnostics,” Laje says.

According to Laje, several companies have expressed interest in taking the study findings further. “We have been approached by industry but these markers have not yet been licensed,” Laje adds.

In the study, published in the August issue of the American Journal of Psychiatry, researchers examined the DNA of 1,816 patients who had participated in the Sequence Treatment Alternatives to Relieve Depression study, or STAR*D, a seven-year, $31 million study across 41 sites in the US looking at non-psychotic major depression.

The STAR*D trial found that depressed patients who don’t benefit from the first medication prescribed to them may benefit from subsequent treatments.

Scientists from NHGRI, NIAAA, Mount Sinai School of Medicine, and University of Texas Southwestern Medical Center also contributed to the research.

Turna Ray


Gene Logic Touts Progress in Drug Repositioning

Gene Logic said in July that it plans to sell its genomics division and focus its resources on becoming a pharmaceutical development company based on its drug repositioning business.

In line with that strategy, the company for the first time provided information about the progress of its drug repositioning effort, disclosing that a candidate licensed from Millennium showed efficacy “at relevant doses” in in vivo testing for inflammatory bowel disease.

“Our strategic policy comprises two terms,” Gene Logic CEO Charles Dimmler said during an earnings call. “First we focused our resources tightly to become a pharmaceutical development company. We based this on our proprietary drug positioning program in Cambridge. And second, we are exploring a wide range of alternatives to optimize the value of our genomics assets.”

Gene Logic has been hinting at the possibility of selling off its genomics business for several months now. In April, the company said it was “considering strategic alternatives” for the unit, and two months before that, the firm said it might create “a spin-off entity with a retained equity position or other alternative structures to capture value for Gene Logic.”

Over the past year, Gene Logic has been in a continual state of flux, repeatedly repositioning itself by chipping away at its various divisions. Last November, the company got rid of its preclinical division, refocused its genomics arm, and said it was pinning its hopes on its drug repositioning activities.

Now, the company plans to concentrate on its drug repositioning business, aspiring to transform itself into a pharmaceutical development company through partnerships with pharma. While Gene Logic has announced drug repositioning partnerships with Pfizer, Roche, Lilly, Organon, and most recently Abbott and H. Lundbeck AS, the company has been tightlipped about its drug repositioning platform and the drug candidates it is rescuing.

 — Turna Ray

Short Reads

Ensemble Discovery announced a collaboration with Roche to develop a test that may be used to analyze combinations of specific receptors that could help select cancer patients most likely to respond to particular therapies. Under the agreement, the companies will use Ensemble’s DNA Programmed Chemistry technology to study combinations of epidermal growth factor receptors that are found in some cancer tissues.

India’s GVK Biosciences inked an agreement that will give the US Food and Drug Administration access to the company’s Clinical Biomarker Database. The FDA will use GVK’s database, which holds  information from published literature relating to clinical and pre-clinical biomarkers, as part of its Voluntary Exploratory Data Submission Program and in internal research projects.

Nanosphere, a molecular diagnostics developer, filed a prospectus for its initial public offering with the US Securities and Exchange Commission. The company, which did not set a price for its stock, hopes to raise at least $90 million to fund R&D as well as sales and marketing.

Omicia received a small business technology transfer grant worth $187,700 from the the National Heart, Lung, and Blood Institute at NIH to support a collaboration with Johns Hopkins University to study the genetic underpinnings of cardiovascular disease.

Global Lifescience Solutions, a segment of non-profit safety testing firm NSF International, will partner with the Michigan High Throughput Screening Center in Kalamazoo, Mich., to offer screening services that may help companies identify potential leads for drug discovery. Through the partnership, MHTSC will add high-content screening services from GLS to its current menu of high-throughput screening services.

Curidium Medica, a UK-based developer of blood-based diagnostics for disorders of the central nervous system, said it has joined the Personalized Medicine Coalition.
The coalition is a US-based nonprofit that aims to advance personalized medicine concepts and products and is composed of pharmaceutical, biotechnology, diagnostics, and information technology companies.

Clarient acquired an exclusive license to Health Discovery Corporation’s prostate cancer marker and plans to develop and commercialize a multi-gene test based on the marker. Through the deal, HDC will receive a 30 percent royalty payment for all prostate cancer tests Clarient performs for third parties using the technology.

Digene extended by four years a three-year marketing agreement with Quest Diagnostics through which Quest will market Digene’s test for human papillomavirus. Digene will continue to supply Quest’s labs with the instrumentation and reagents for HPV testing.


US Patent 7,256,020. Methods and compositions for detecting target sequences. Inventors: Victor Lyamichev, Bruce Neri, Jeff Hall, and Andrew Lukowiak. Assignee: Third Wave Technologies. Issued: August 14, 2007.

This patent relates to techniques “for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. ... For example, in some embodiments, a 5’ nuclease activity from any of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.”

US Patent 7,256,277. Nucleotide and protein sequence of mammastatin and methods of use. Inventor: Paul Ervin, Jr. Assignee: Regents of the University of Michigan. Issued: August 14, 2007.

The patent covers “a nucleic acid sequence encoding Mammastatin, a specific mammary cell growth inhibitor,” according to the abstract, adding that “mammary cancer cells are inhibited in their growth by the administration of phosphorylated mammastatin.”

Jargon Watch


A portmanteau of “therapeutic” and “diagnostic,” the concept behind theranostics is to develop diagnostic tests in conjunction with new therapeutics, rather than developing a companion diagnostic for a treatment that’s already on the market. The diagnostic and therapeutic would be marketed together, representing another step forward in the goal of individually tailored treatment for patients.


Instead of the blockbuster drugs that have dominated the pharma industry in recent years, “niche-busters” are therapeutics that are expected to be highly successful within a very targeted sub-population by relying on biomarkers to stratify patients.

Data Points

$20 million

Oncology products maker Cell Therapeutics agreed to buy Systems Medicine, a pharmacogenomics-focused cancer drug company based in Arizona, in a stock merger valued at around $20 million.

26 percent

Third Wave Technologies reported that revenue from clinical products rose 26 percent to $6.3 million during the second quarter, compared to the same quarter the year before. Meanwhile, revenue from research products fell 37 percent to $1.1 million.

The Scan

Cell Signaling Pathway Identified as Metastasis Suppressor

A new study in Nature homes in on the STING pathway as a suppressor of metastasis in a mouse model of lung cancer.

Using Bees to Gain Insights into Urban Microbiomes

As bees buzz around, they pick up debris that provides insight into the metagenome of their surroundings, researchers report in Environmental Microbiome.

Age, Genetic Risk Tied to Blood Lipid Changes in New Study

A study appearing in JAMA Network Open suggests strategies to address high lipid levels should focus on individuals with high genetic risk and at specific ages.

Study Examines Insights Gained by Adjunct Trio RNA Sequencing in Complex Pediatric Disease Cases

Researchers in AJHG explore the diagnostic utility of adding parent-child RNA-seq to genome sequencing in dozens of families with complex, undiagnosed genetic disease.