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The Ongoing Collaboration Aims to Exploit the High Throughput, Robustness and Ease of Use of MALDI-TOF Instruments

At the 12th HUPO World Congress, Bruker Corporation (NASDAQ: BRKR) recently announced the start of a second-phase collaboration agreement with SISCAPA Assays Technologies, Inc. (SAT). The ongoing collaboration aims to exploit the high throughput, robustness and ease of use of MALDI-TOF instruments as an alternative to nano-LC-MS technology currently used in many SISCAPA assays.

AB SCIEX Proteomics Scientist Wins HUPO 2013 Science and Technology Award

The Human Proteome Organization (HUPO) recently awarded Christie Hunter, Ph.D, director of proteomics applications at AB SCIEX, its 2013 Science and Technology Award at an award ceremony during last week’s HUPO 2013 conference in Japan. Dr. Hunter was recognized for her contributions to the development and commercialization of a breakthrough approach for targeted proteomics. The analytical strategy of targeted proteomics was recently named “Method of the Year” by Nature Methods.

Targeted proteomics is a standardized, biological research workflow that focuses on reproducibly quantifying a specific subset of proteins within a sample. It generates data that is vital for biologists to answer hypothesis-driven, biological questions.

A decade ago, proteomics research was dominated by discovery workflows, which provided valuable information on a single sample but lacked the reproducibility to generate robust quantitation across a larger sample set. New innovation was needed at the time to move the field beyond simply producing large lists of identified proteins and toward providing highly quantitative answers.

This led to the development of a multiple reaction monitoring (MRM)-triggered, tandem mass spectrometry (MS/MS) workflow at AB SCIEX to rapidly create high sensitivity MRM assays to target peptides that are unique to their associated proteins. This workflow was made possible by the combination of triple quadrupole and linear ion trap functionality in a single system called the AB SCIEX QTRAP® System.

Dr. Hunter ‒ in collaboration with researcher Dr. Leigh Anderson, the founder of the Plasma Proteome Institute and head of SISCAPA Assay Technologies ‒ pioneered a workflow that applied MRM to the targeted quantification of proteins and peptides in plasma by mass spectrometry. In their initial publication[1], Dr. Hunter and Dr. Anderson demonstrated that a targeted workflow could be applied to multiplexed quantitation of proteins in human plasma with high reproducibility and high confidence in the results.

The impact of the paper resulted in broad adoption of the MRM technique around the world to accelerate the verification and validation of putative protein biomarkers, generating more than 800 citations, according to Google Scholar. Less than a decade after this important work, most proteomics laboratories today use a triple quadrupole-based mass spectrometer to perform MRM analysis.

“We congratulate Dr. Christie Hunter on receiving such a prestigious award from HUPO in recognition of her significant contributions to the rise of targeted proteomics as a viable technique to advance biomarker research,” said Dave Hicks, Vice President and General Manager of the Pharmaceutical and Academic Business at AB SCIEX.

“Dr. Hunter and her AB SCIEX colleagues continue to participate in exciting collaborations with leading proteomics researchers around the world to drive new innovations in software, chemistries and instrumentation that further expand quantitative proteomics workflows for the growing community of mass spectrometry users at large,” added Hicks.

Currently, Dr. Hunter is playing a pivotal role in the development of higher specificity workflows for targeted protein quantitation to overcome situations where sensitivity is limited by interferences or background. She is involved in the investigation of the utility of differential mobility separations for added selectivity of quantitation of peptides in complex mixtures. She is also working to enhance data-independent acquisition strategies, such as SWATHTM Acquisition, for quantitative proteomics to increase the multiplexing and reproducibility that can be achieved in a single experiment.

Source: AB SCIEX

Comprehensive Parkinson’s Biomarker Test Has Prognostic and Diagnostic Value, Penn Medicine Team Reports

Perelman School of Medicine researchers at the University of Pennsylvania report the first biomarker results reported from the Parkinson’s Progression Markers Initiative (PPMI), showing that a comprehensive test of protein biomarkers in spinal fluid have prognostic and diagnostic value in early stages of Parkinson’s disease. The study is reported in JAMA Neurology.

Compared to healthy adults, the study found that people with early Parkinson’s had lower levels of amyloid beta, tau and alpha synuclein in their spinal fluid. In addition, those with lower concentrations of tau and alpha synuclein had greater motor dysfunction. And early Parkinson’s patients with low levels of amyloid beta and tau were more likely to be classified as having the postural instability-gait disturbance- dominant (PIGD) motor type of disease, where falling, freezing, and walking difficulty are common.

“Biomarkers for Parkinson’s disease such as these could help us diagnose patients earlier, and we’ve now shown that the simultaneous measurement of a variety of neurodegenerative disease proteins is valuable,” said study senior author Leslie M. Shaw, PhD, professor of Pathology and Laboratory Medicine at Penn Medicine. Dr. Shaw and John Q. Trojanowski, MD, PhD, director of the Penn Udall Center for Parkinson’s Research, are co-leaders of the Bioanalytics Core for the Parkinson’s Progression Markers Initiative, an international observational clinical study sponsored by The Michael J. Fox Foundation for Parkinson’s Research.

The team evaluated spinal fluid collected from baseline visits of the first 102 PPMI participants – 63 with early, untreated Parkinson’s disease and 39 healthy controls. The spinal fluid was evaluated for levels of five biomarkers: amyloid beta, total tau, phosphorylated tau, alpha synuclein and the ratio of total tau to amyloid beta. Spinal fluid measures of amyloid and tau are currently used in research to distinguish Alzheimer’s disease from other neurodegenerative diseases. In contrast to Alzheimer’s, where tau levels are higher than healthy controls, the study found that early Parkinson’s patients had lower levels of tau than healthy controls. One reason, researchers suggest, could be that interactions between tau and alpha synuclein may limit the release of tau into the cerebrospinal fluid of Parkinson’s patients.

“Through PPMI, we are hoping to identify subgroups of Parkinson’s patients whose disease is likely to progress at a different rate, as early as possible,” said Dr. Trojanowski. “Early prediction is critical, for both motor and dementia symptoms.”

The Parkinson’s PIGD motor subtype has been associated with a more rapid cognitive decline as well as greater functional disability. Using the biomarker test, this initial study found that levels of all spinal fluid biomarkers were lower in the PIGD motor subtype than other types of PD as well as healthy controls. In addition, amyloid beta and phosphorylated tau were at lower levels in the PIGD motor subtype, but were no different in tremor or indeterminate subtypes compared to normal controls.

This spinal fluid testing procedure is only being used in research studies, and will be continued to be evaluated and validated in a larger study of the PPMI cohorts.

In addition to leading the Bioanalytics Core of PPMI, Penn’s Parkinson’s Disease and Movement Disorders Center is one of the two dozen trial sites where volunteers are evaluated throughout the PPMI study. The Penn PDMDC has been part of the PPMI group studying people with early Parkinson’s disease as well as healthy adults since 2010, and began enrollment for a new, pre-symptomatic arm of the study in the summer of 2013. The pre-motor arm of PPMI is enrolling participants who do not have Parkinson’s disease and are living with one of three potential risk factors for PD: a reduced sense of smell (hyposmia); rapid eye movement sleep behavior disorder (RBD; a disorder in which the individual acts out his/her dreams); or a mutation in the LRRK2 gene (the single greatest genetic contributor to PD known to date).

“In addition to biomarker tests, validating risk factors could enable earlier detection of the disease and open new avenues in the quest for therapies that could slow or stop disease progression,” said PPMI trial site study leader Matthew Stern, MD, professor of Neurology and director of Penn’s Parkinson’s Disease and Movement Disorders Center.

Study: Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease [JAMA Neurology]

Source: Penn Medicine

Biomarkers Predict Time to Ovarian Cancer Recurrence

Ovarian cancer often remains undetected until it is at an advanced stage. Despite positive responses to initial treatment, many patients are at risk of tumor recurrence. A multitude of genetic markers have been implicated in ovarian cancer prognosis. However, the genetic testing required is not practical or affordable in a clinical setting.

In this issue of the Journal of Clinical Investigation, Roel Verchaak and colleagues at the MD Anderson Cancer Center identify protein biomarkers that are predictive for time of ovarian cancer recurrence and develop a PRotein-driven index of OVARian cancer (PROVAR).

Using PROVAR, the authors were able to discriminate between patients with high and low risk of cancer recurrence, as well as short-term and long-term survival prognosis. In combination with genetic diagnosis, analysis of protein biomarkers may be useful in predicting outcome and determining a treatment plan for ovarian cancer patients.

Study: Predicting time to ovarian carcinoma recurrence using protein markers [Journal of Clinical Investigation]

Source: EurekAlert!

DaVita Labs and Myriad RBM Announce Biomarker Research Collaboration

DaVita Labs, a unit of DaVita HealthCare Partners Inc. (NYSE:DVA) and Myriad RBM, a wholly-owned subsidiary of Myriad Genetics (Nasdaq:MYGN) announced today a research collaboration to conduct protein biomarker discovery research with the goal of developing and commercializing diagnostic tests that could benefit in the treatment of dialysis patients.

DaVita and Myriad have identified potential opportunities where novel diagnostic tests utilizing blood-based protein biomarkers could improve the quality of life for patients and potentially lower overall healthcare costs. The primary area of focus will include the prediction of vascular access failure.

“This collaboration uses DaVita’s proprietary biorepository that is intended to facilitate innovative research across renal disease,” said Chris Rucker, president of DaVita Labs and DaVita Clinical Research. “Myriad recognizes the value that the biorepository can bring to research and development activities, and we look forward to collaborating with Myriad on the research and development of novel diagnostics that could transform our industry.”

“We are enthusiastic to collaborate with a company of the caliber of DaVita in the field of dialysis, one of the largest health care service markets,” said Craig Benson, president Myriad RBM. “We have extensive experience with research in kidney disease and inflammatory markers that we believe could increase the quality of care for dialysis patients.”

Specimens from the DaVita biorepository will be processed on the Myriad RBM DiscoveryMAP® platform for the quantification of more than 300 important proteins. DiscoveryMAP analyzes protein biomarkers correlated with inflammatory, metabolic and renal disease conditions that could have meaningful utility as diagnostic criteria for dialysis patients. Myriad is expected to begin processing specimens associated with this collaboration in fiscal year 2014.

Source: Myriad Genetics