FierceBiomarkers


March 28, 2012

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Today's Top Stories
1. Circulating cells signal upcoming heart attack
2. Researchers link miRNAs to heart attack risk
3. The magnetic attraction of blood biomarkers
4. Brain atrophy links with tau biomarker in Alzheimer's progression
5. Faulty genes may trigger early autistic brain growth

Editor's Corner: Omics tests need validation

Also Noted: Spotlight On... DiaGenic, GE combine genes and imaging for AD
Enterome raises €5.5m funding to validate biomarkers; Fasting blood glucose signals depression in elderly; and much more...

News From the Fierce Network:
1. Fierce's 5 Drug Delivery Companies to Watch
2. Novartis leads $12.5M A round for antibody diagnostics start-up ImaginAb
3. NEJM: Blame chronic diarrhea on mutated gene



Editor's Corner

Omics tests need validation

By Suzanne Elvidge Comment | Forward | Twitter | Facebook | LinkedIn

Biomarkers are being used every day to target development of new drugs and to diagnose and guide treatment of disease, and they have the potential to be ever more powerful as research into genomics, proteomics and all the other omics continues. However, as a new report from the Institute of Medicine recommends, there need to be solid evaluation and validation processes in place before any of these tests make it to the clinic.

These concerns and recommendations arise from recent findings that some personalized medicine tests that have been based on omics research have not proved valid. The issues arose from claims from researchers at Duke University about genomic tests predicting efficacy of cancer chemotherapies in certain patient groups. There were problems with data and methodologies, and because these were not spotted, or not acted upon, papers were published that had to be retracted, patients were enrolled into inappropriate clinical trials, and companies were launched prematurely. These tests have now been acknowledged as invalid.

To avoid this happening again, which could potentially put patients at risk and place doctors in a vulnerable position, the report recommends that investigators should ensure that their data and computational processes go through independent scrutiny, and journal editors should require researchers to disclose their data and codes at the time of a paper's submission. As part of the process, researchers should discuss the tests with the regulatory authorities at the beginning of validation studies and not change the tests during clinical trials without letting the authorities know.

The key recommendation is for integrity and transparency at every stage of the process and reporting and investigating any conflicts and issues, from beginning to end. Even journal editors (and newsletter editors) can play a role here, spotting and reporting errors.

"We hope that this report will help all members of the investigative team understand the entire pathway of translating omics discoveries into clinical tests and recognize and avoid the potential pitfalls at each stage," said committee chair Gilbert Omenn, professor of internal medicine, human genetics, and public health, and director, Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor. "We believe that past problems, such as the Duke case, could have been prevented had a clearly defined process been available and been utilized. Scientific and clinical progress in omics test development will be accelerated if these recommendations are broadly adopted."

Want to read more about personalized medicine? In the ebook Companion diagnostics: The future of medicine, we've looked at the development of targeted drugs and companion diagnostics, including the successful and not-so-successful projects, and what issues (and opportunities) there will be for regulators, biopharma companies and payers moving into the future. -- Suzanne Elvidge (email)

Read more about: Biomarkers, personalized medicine
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Today's Top News

1. Circulating cells signal upcoming heart attack

By Suzanne Elvidge Comment | Forward | Twitter | Facebook | LinkedIn

Heart attacks can be devastating for the family and the patient, and around half of heart attacks or strokes can occur in people who don't seem to have any obvious risk factors. A blood test that detects abnormal cells in the blood could pinpoint people at risk of a heart attack, and has been described as the holy grail of cardiovascular medicine.

Most people's arteries have levels of thickening or hardening, where the walls fur up with cholesterol (atheromatous plaques). If these swellings rupture, this can cause a heart attack, also called an acute myocardial infarction (MI). According to research headed up by Scripps Translational Science Institute (STSI), odd-shaped or overly large circulating endothelial cells (CEC) could signpost an arterial plaque rupture. This could lead to a simple blood test warning of a high risk of a heart attack in the near future.

In a group of 50 heart attack patients seen in emergency rooms and 44 healthy people, the numbers of CECs, which normally line the arteries of the heart, were significantly higher in the blood of heart patients than in the healthy individuals, and many of the cells were misshapen, enlarged or had three or more nuclei.

"The CECs are supposed to be like insulation for the artery," Eric Topol, the study's principal investigator and director of STSI, told the San Diego Union-Tribune. "When they start to slough off, become numerous, misshapen and have multiple nuclei, it is sign that a heart attack is imminent. They're a biomarker." Topol suggests that the cells could start to break off the artery lining days or weeks before the heart attack happens, making this a potential early warning signal.

Collaborator Sharp HealthCare believes that a test could be available within a year or two. Current tests just indicate whether a patient has actually had a heart attack--if this test comes through it could allow doctors to prevent a heart attack from happening, rather than dealing with the problems after it has actually happened. This could not only reduce the risk of death or disability for the patient but also significantly cut healthcare costs and reduce the social burden of lost days working.

- read the press release
- see the abstract from Science Translational Medicine
- check out the article in the San Diego Union-Tribune

Related Articles:
Inflammatory protein marks heart disease
Positive results for biomarker based diagnostic CardioSCORE
Heart attack? No, it's just a spinning class
Gene sleuths find biomarkers for silent killer atherosclerosis

Read more about: heart disease biomarkers, heart attack
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2. Researchers link miRNAs to heart attack risk

By Suzanne Elvidge Comment | Forward | Twitter | Facebook | LinkedIn

This week circulating cells have been linked to heart attacks and now microRNAs--fragments of non-coding genetic material--found in the blood show potential as a screening tool to predict imminent heart attacks. The researchers, from Intermountain Medical Center in Murray, UT, looked for traces of 6 known miRNA biomarkers in blood samples from 85 cardiac patients. The blood samples included ones taken up to a week before a heart attack or within 36 hours of having had a heart attack. Other samples were from healthy patients or people with heart problems but no sign of a heart attack.

In patients who would go on to have a heart attack within a week, levels of three of the miRNAs (miR-122, miR-145 and miR-375) were lower than in the other groups, with miR-122 reduced to the greatest extent. While the 6 biomarkers used were already associated with patients who had already had a heart attack, this was the first time that these miRNAs have been linked with heart attack risk in patients that appeared healthy. The results were presented at the American College of Cardiology's 61st Annual Scientific Session.

MiRNAs are used as "switches" for genes, and these results could help pinpoint which genes might be linked with heart attacks.

"We don't know exactly which genes are controlled by these microRNAs, but this study gives us a good starting point for looking more deeply into the ways they influence the heart," says John Carlquist, director of Intermountain Healthcare's Cardiovascular Molecular and Genetic Laboratory at LDS Hospital, one of the study's authors.

Measuring the levels could also be used to find those people who might go on to have a heart attack, perhaps through regular screening, triggering even closer monitoring or preventive treatment.

"About half of all heart attacks occur in patients with no previous signs of heart disease. The heart attack is a surprise, and very often it's deadly," says Dr. Jeffrey L. Anderson, chief of cardiovascular research at the Intermountain Medical Center Heart Institute and one of the study's authors. "This project has a lot of promise in helping us develop a way to identify these patients who don't show any obvious signs but are at imminent risk of suffering a heart attack."

- read the press release

Related Articles:
Genetic biomarkers could help detect food allergy
Blood miRNAs can affect cancer biomarker studies
NIH awards $500,000 to various miRNA biomarker studies
New technique makes it easier to detect miRNA biomarkers
MicroRNAs are potential biomarkers for heart disease, cancer

Read more about: miRNA
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3. The magnetic attraction of blood biomarkers

By Suzanne Elvidge Comment | Forward | Twitter | Facebook | LinkedIn

Biomarkers are an exciting part of medical research--they must be, otherwise you wouldn't be reading this story. But finding them in tissues, blood and other body fluids isn't always easy, especially at low levels, and can involve tricky and time-consuming purification steps. Using magnetic particles tagged with antibodies in a fast, simple, one-step assay could make this a whole lot easier.

Dutch researchers from Philips Research and Eindhoven University of Technology created magnetic nanoparticles (particles less than around 100 nanometers in diameter) and coated these with antibodies directed to specific protein biomarkers. The test took only 14 minutes to detect very low levels of the protein prostate cancer biomarker PSA (prostate-specific antigen) straight from human plasma with no preparation or dilution needed. Existing tests for PSA can take hours and are not as sensitive.

The test uses two antibodies that link with different parts of the PSA molecule. The magnetic pulses line the rods up, helping them to link with the PSA at very low levels, and the size of the clusters indicates the levels of PSA.

The researchers used PSA to demonstrate the technique--it could have potential in a range of diagnostics. Its level of sensitivity could allow physicians to detect biomarkers at low levels and therefore find disease at an early stage, or could help researchers to find new low-level biomarkers that could be targets for treatment or new diagnostics.

- see the abstract
- check out the article in Chemical & Engineering News

Related Articles:
PSA testing has no survival benefit, task force says
Partnership searches for better prostate cancer biomarker
DNA biomarker could complement PSA in prostate cancer diagnosis
Gold nanoparticles detect PSA for breast cancer

Read more about: prostate cancer
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4. Brain atrophy links with tau biomarker in Alzheimer's progression

By Suzanne Elvidge Comment | Forward | Twitter | Facebook | LinkedIn

The memory loss linked with mild cognitive impairment (MCI) can seem nothing much more than a frustration--the odd senior moment, forgotten names here and there, the occasional missed appointment--and it might be the result of nothing more than a bout of stress. However, it can have a more sinister side when it signals the approach of Alzheimer's disease. The progression from MCI to Alzheimer's disease is faster in some people than in others, from as short as a few months to as long as 10 years. Researchers in the Netherlands have pinpointed a couple of biomarkers that could help to find the people most at risk.

In a paper published in The Journal of Alzheimer's Disease, the researchers looked at 91 people with mild cognitive impairment and assessed a number of factors to see if they could be linked with different speeds of progression. The patients that went downhill more quickly were more likely to have brain shrinkage (atrophy) and higher levels of tau protein in their cerebrospinal fluid.

As well as better diagnostics, physicians working with people with mild cognitive impairment need better predictive biomarkers that can indicate how quickly (or slowly) people might progress to full-blown Alzheimer's disease, to help them choose treatment and find the most appropriate support for patients and their families. However, it's still at an early stage and researchers are aware that further work is needed.

- read the press release
- see the abstract

Related Articles:
Alzheimer's disease imaging signature predicts cognitive decline
Study links BMI to Alzheimer's, MCI
CSF biomarkers could differentiate types of dementia
Biomarker may signal cognitive decline

Read more about: tau protein, Alzheimer's
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5. Faulty genes may trigger early autistic brain growth

By Suzanne Elvidge Comment | Forward | Twitter | Facebook | LinkedIn

Autism seems to be inherited, but until now, little has been known about the genetics behind the disorder. In a study at the University of California, San Diego School of Medicine, researchers have linked specific genetic changes with the abnormal early brain growth seen in children with autism. The brain seems to grow too quickly, and then starts to lose connections between brain cells. This is particularly in an area of the brain known as the prefrontal cortex, which is associated with social, communication and cognitive development, which ties in with the symptoms of the syndrome.

By carrying out analyses of the DNA in samples from this area of the brain from children and young people and comparing it with adults with autism syndrome disorder, they found changes in the genes that regulate the number of cells and the patterns of cells in the young people with autism. In the adults with autism, this part of the brain had changes in signaling. Both groups also had lower levels of the genes that coordinate cell repair.

"Our results indicate that gene expression abnormalities change across the lifespan in autism, and that dysregulated processes in the developing brain of autistic patients differ from those detected at adult ages," said Eric Courchesne, Ph.D., director of the Autism Center of Excellence at UCSD. "The dysregulated genetic pathways we found at young ages in autism may underlie the excess of neurons--and early brain overgrowth--associated with this disorder."

Autism seems to be a recurring theme in biomarker research at the moment, with researchers moving closer to blood-based or imaging-based tests for this distressing developmental disorder. Finding the biomarkers, targets and processes underlying autism could help find better ways to identify and treat--or even maybe to prevent--the abnormal brain growth that seems to be a common factor in the disorder.

- read the press release
- see the abstract
- check out the article in Scientific American

Related Articles:
New biomarkers could mean a blood test for autism
Berg Pharma brings biomarkers for autism a step closer
Imaging biomarker shows autism in infancy
Immune biomarker could link to autism
Brain scans reveal neural signatures for autism

Read more about: San Diego, autism
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Also Noted

SPOTLIGHT ON... DiaGenic, GE combine genes and imaging for AD

Alzheimer's disease biomarkers feature regularly in FierceBiomarkers, from mitochondrial changes to beta-amyloid expression. Taking a combined approach, Norwegian company DiaGenic is uniting its expertise in peripheral gene expression profiling with GE Healthcare's PET imaging expertise in a collaboration to create a blood-based test to check for Alzheimer's disease in patients with mild cognitive impairment (MCI). The potential test will use GE's PET imaging agent [18F] flutemetamol, which is in Phase III trials, and could help point out early-stage disease, improving support and treatment choices for these vulnerable patients. "For this project, we aim to recruit 180 individuals with amnestic MCI, together with 30 patients with clinically diagnosed mild to moderate AD," said Dr. Oskar Hansson of Lund University and Skåne University Hospital and principal investigator of the study. "Clinical assessment together with high-quality blood and imaging tests for the very early stages of AD will bring tremendous value to the clinicians and drug developers." Release

> Paris-based biomarker company Enterome has raised €5 million ($6.6 million) to validate its biomarkers and help move them toward diagnostic tests. Article

> A panel of 10 serum biomarkers could support CT screening in diagnosis of lung cancer in high-risk people. Article

> Fasting blood glucose signals more than diabetes; it could diagnose depression in elderly people. Article (sub. req.)

> The leukocyte-based biomarker BORIS is in a trial as a potential early breast cancer biomarker in women with high familial risk of the disease. Article

> Qiagen and the Bio-X Center of Shanghai Jiao Tong University are to set up a translational medicine base in Shanghai; the projects will include biomarker validation. Article

> An ER stress biomarker could pick up diabetes before symptoms start, if mouse model findings transfer across to the clinic. Press release

> Soluble CD14, a biomarker in babies' umbilical cord blood, could signpost their risk of cough and wheeze at one year. Article

> A new method to measure beta amyloid, using flow cytometry, could help develop Alzheimer's disease drugs and diagnostics. Press release

> Magnetic resonance imaging can "see" the oncometabolite 2-hydroxyglutarate; this technique could have potential in brain tumor diagnosis. Press release | Abstract

> Troponin-I assay could predict risk of cardiovascular death up to 15 years in the future. Press release

> New autism mouse model has suggested a link between early disruptions in serotonin signaling in the brain and autism spectrum disorder. Press release

> Levels of granulocyte colony-stimulating factor (G-CSF) could be a biomarker for the severity of stroke. Abstract

And Finally… State wealth could be linked with cardiac biomarkers. Article


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This FiercePharma eBook examines Big Pharma's need for technology to give new life to old drugs, and potentially deliver their next breakthrough medicines. This report covers some of the market opportunities, business strategies, and key innovations in the oral drug delivery field.