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Vanda Pharmaceuticals, Bill and Melinda Gates Foundation, Massachusetts General Hospital, DeCode Genetics, Center for Molecular Medicine, AviaraDx, Interleukin, Access Business Group International, University of Chicago, Affymetrix

Vanda Publishes Study for Investigational PGx-based Schizophrenia Drug
A study conducted by Vanda Pharmaceuticals, reported in the journal Pharmacogenomics, suggests that a genetic variation in the ciliary neurotrophic factor gene may affect response to antipsychotic treatment with the drug iloperidone.
The study involved patients with acute symptoms of schizophrenia treated either with iloperidone or placebo. The study results showed “significant improvement from baseline in all symptoms across all patient genotypes of CNTF,” the company said in a statement. More commonly called Fiapta, iloperidone is an atypical antipsychotic agent currently under review with the US Food and Drug Administration.
According to the company, “CNTF is a neurotrophic factor important for neuronal survival and recovery after injury.” Approximately 75 percent of the population carry two intact copies of the CNTF protein while 25 percent carry one or two truncated copies of the protein.
In the study, patients carrying both intact copies of CNTF had “significantly better” outcomes in terms of symptom improvement with Fiapta treatment than with placebo in symptom improvement. However, placebo-treated and Fiapta-treated patients with one truncated copy of the CNTF protein had a significant improvement from baseline “indicating an enhanced placebo response among this group of patients.”
Steven Potkin, director of the Clinical Psychiatric Research at the University of California, Irvine, said that the “results of this prospective study on the genetics of drug response offer tantalizing clues on the involvement of neurotrophic factors in schizophrenia.”
Iloperidone comes to Vanda by way of a sublicense from Titan, who in turn licensed the drug from Novartis. According to Vanda, Titan is entitled to between eight percent and 10 percent of iloperidone royalties.
The company has yet to elucidate plans for a potential companion diagnostic for iloperidone. The company has suggested that any test to determine iloperidone administration may be specifically for that drug and would not work across the class of atypical antipsychotic drugs.

Gates Foundation Awards $20.5M to Study Genetics of HIV Controllers
The Bill and Melinda Gates Foundation has awarded $20.5 million to the Massachusetts General Hospital and partnering institutions to study the genomes and immune systems of people whose bodies naturally control HIV without drugs.
The five-year grant will expand an ongoing international effort to study the genes of these so-called HIV controllers, who are HIV-positive but have remained healthy for as long as 25 years without medication.
These patients represent a minority of HIV-positive people. One group, called viremic controllers, are able to maintain viral loads below 2,000 copies/ml, while another group, called aviremic or "elite" controllers, can maintain viral loads of less than 50 copies/ml. It is estimated that only 1 in 300 HIV-positive individuals is an elite controller.
The Gates Foundation award will support the expansion of the HIV Controllers Study, which MGH launched in 2006 with a $2.5 million grant from the Mark and Lisa Schwartz Foundation. The program has already recruited almost 1,000 controllers and plans to expand the study group to 2,000 participants – 1,000 elite controllers and 1,000 viremic controllers.
The researchers will genotype 650,000 SNP sites in the genome of each participant and will compare the genotypes of the HIV controllers against those of 3,000 people who are suffering from progressive HIV infection in order to identify genetic factors that may be associated with viremic control.
“We believe that it is critical to understand how these individuals – who are maintaining viral levels so low that transmission and disease progression should decrease markedly – are keeping the virus in check and preventing it from causing disease,” said Bruce Walker, director of the Partners AIDS Research Center at MGH and the principal investigator on the grant.
“Since other approaches to vaccine development have not been successful, uncovering how some humans are able to coexist with the virus without developing AIDS, in spite of not receiving any therapies, is critical,” explained Steven Deeks, a collaborator in the study at the University of California at San Francisco.
Several other institutions are also collaborating in the project, including the Broad Institute of Harvard University and Massachusetts Institute of Technology; Brigham and Women’s Hospital; the University of KwaZulu Natal, Durban, South Africa; the National Cancer Institute; Rockefeller University; the University of California at San Diego; the University of Lausanne, Switzerland; and the US Defense Institute for Medical Operations.

DeCode Lays Off 14 Percent of Staff to Conserve Cash
DeCode Genetics has laid off 60 employees, or around 14 percent of its staff, in an effort to ensure it has enough cash to last two years, the company disclosed this week in a filing with the US Securities and Exchange Commission.  
The company said in the filing that the layoffs are “in line with its longstanding goal of ensuring that it has cash resources to last approximately two years.”
Almost all of the affected employees are in the company’s Reykjavik, Iceland, facilities, DeCode said.
Prior to the layoffs, the company employed 429 full-time staff. According to DeCode’s most recent annual report, 143 of those staffers were employed in the US and 286 in Iceland.
As of Sept. 30, 2007, the most recent period for which financial data is available, DeCode had cash and cash equivalents of $45.8 million and $118.6 million in cash, cash equivalents, and investments.
The company said in its quarterly report for that period that it will “require significant additional capital" to advance its drug development pipeline, "and so we will continue to investigate additional avenues of financing, such as further public or private equity offerings, additional debt financing, other forms of financing, or added collaborations and licensing arrangements.”
DeCode acknowledged, however, that “no assurance can be given that additional financing or collaborations and licensing arrangements will be available when needed, or that if available, will be obtained on favorable terms,” and warned that if unable to raise additional cash, “we may have to curtail operations or attempt to raise funds on unattractive terms.

Center for Molecular Medicine to Offer Three AviaraDx Cancer Tests
The Center for Molecular Medicine said this week that it will offer three cancer tests developed by AviaraDx in an effort to help physicians make more informed decisions in managing oncology patients.
Under the agreement, CMM said it will advise physicians on the value and clinical utility of the AviaraDx tests, and will coordinate sample preparation and shipping. AviaraDx will analyze the tumor samples in its CLIA-certified, CAP-accredited laboratory.
The agreement covers three tests: CancerTYPE ID, which pinpoints a tumor's organ of origin; H/I, which uses a two-gene expression signature as an independent predictor of treatment outcome for breast cancer patients receiving endocrine therapy; and Molecular Grade Index, or MGI, which uses a five-gene signature to discriminate between tumor grades 1 and 3 and to reclassify grade 2 tumors as either grade-1-like or grade-3-like.
CMM said the AviaraDx cancer tests will complement the CellSearch suite of tests from Veridex that it already offers as part of its cancer-management portfolio.
“While the AviaraDx tests will typically be used in the earlier stages of a patient's diagnosis and treatment, the CellSearch System helps physicians more effectively manage patients with more advanced metastatic colorectal, breast, and prostate cancer,” CMM said in a statement.

Interleukin Genetics Inks $1.2M Research Agreement with ABG
Interleukin Genetics has signed a $1.2 million research agreement with Alticor subsidiary Access Business Group International to search for genetic variations in four main disease areas: osteoporosis, cardiovascular disease, nutrigenomics, and dermagenomics.
Under the terms of the agreement, Interleukin will conduct studies to correlate SNPs with the risk of osteoporosis or cardiovascular disease in Asian populations, and will also conduct additional studies in North American populations to identify genetic factors that influence skin appearance and athletic performance in response to nutritional products.
The company said that around $800,000 of unspent funding from earlier research pacts with Alticor will be credited against the costs of the ABG agreement.
This is the eighth research agreement between Interleukin Genetics and Alticor. Earlier agreements led to the commercialization of a proprietary genetic test for the risk of early heart disease, a nutritional supplement for those testing positive for the heart risk factor, as well as a general nutrition test panel.

Gene Expression Study of African, European-Descended Populations May Provide Clues on Drug Response
African and European-descended populations have different levels of gene expression, particularly for genes linked to ribosome biogenesis and antimicrobial immunity, according to new research.
Researchers from the University of Chicago and Affymetrix used microarrays and SNP data to compare cell lines from individuals in Utah and Nigeria. They found gene expression differences related to immune response to microbial intruders as well as ribosome biogenesis and other basic cellular functions. The findings, which appeared in the American Journal of Human Genetics last week, may eventually contribute to a population-based or individualized understanding of medicine, the authors suggest.
“We want to understand why different populations experience different degrees of toxicity when taking certain drugs and learn how to predict who might be most at risk for drug side effects,” University of Chicago oncology researcher Eileen Dolan, senior author on the paper, said in a statement.
Suspecting that gene expression differences could be behind such variable drug responses, Dolan and her colleagues compared gene expression between two populations from different parts of the world. They used Affymetrix GeneChip Human Exon 1.0 ST arrays to examine 176 HapMap lymphoblastoid cell lines, created from blood samples from healthy people from 60 nuclear families — 30 Caucasian families from Utah and 30 Yoruban families from Nigeria.
From the 17,879 genes targeted initially, they then focused on the 9,156 that were expressed in all the samples. Almost five percent of those genes were expressed differently in those descended from Europeans than they were in African individuals. On average, the differences in gene expression were approximately 1.26-fold and, based on subsequent experiments, did not seem to stem from copy number variation.
They also looked at whether the genes with the 383 most statistically significant expression differences belonged to certain biological processes. Indeed, the genes tended to cluster to two main processes: ribosome biogenesis and antimicrobial humoral immune response. When they analyzed their results using less rigorous cutoffs, they also detected expression differences in clusters of genes linked to cell-cell adhesion, mRNA catabolism, and tRNA processing.
The team also used genotype information from the International HapMap Project database to look for SNPs that might be contributing to the gene expression differences they detected. That analysis suggested that genetic variation — both in cis-acting and distant trans-acting regulators — contributes to the gene expression differences they observed.
“[I]t is possible that various cis- and trans-acting elements interact as part of a complete network of regulation of complex traits,” the authors wrote. “Our findings of significant SNP and transcript cluster associations, therefore, can be targets for further functional validation to investigate these regulation mechanisms.”

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The Scan

LINE-1 Linked to Premature Aging Conditions

Researchers report in Science Translational Medicine that the accumulation of LINE-1 RNA contributes to premature aging conditions and that symptoms can be improved by targeting them.

Team Presents Cattle Genotype-Tissue Expression Atlas

Using RNA sequences representing thousands of cattle samples, researchers looked at relationships between cattle genotype and tissue expression in Nature Genetics.

Researchers Map Recombination in Khoe-San Population

With whole-genome sequences for dozens of individuals from the Nama population, researchers saw in Genome Biology fine-scale recombination patterns that clustered outside of other populations.

Myotonic Dystrophy Repeat Detected in Family Genome Sequencing Analysis

While sequencing individuals from a multi-generation family, researchers identified a myotonic dystrophy type 2-related short tandem repeat in the European Journal of Human Genetics.