New Biomarker Has Potential For Sideline Diagnosis of Traumatic Brain Injury

MedicalResearch.com Interview with:

Dr-Adrian-Harel.jpg

Dr. Adrian Harel

Dr. Adrian Harel, PhD
Chief Executive Officer
Medicortex Finland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Every 15 seconds, someone in the United States suffers a new head injury. Of the 2.5M people treated in hospital emergency rooms each year, 80,000 become permanently disabled because of TBI. Currently, there are no reliable diagnostic tests to assess the presence or severity of an injury on-site, nor are there any pharmaceutical therapies that could stop the secondary injury from spreading. Accurate diagnostics would benefit especially mild cases of TBI (concussions), which, if occurring repeatedly, may cause neurodegenerative conditions such as Chronic Traumatic Encephalopathy (which is typical for athletes in NFL and Ice-hockey).

We have performed extensive preclinical research comparing fluid biopsies from normal and injured lab animals. The results showed some unique biomarkers released as a biodegradation products after head injury. The data served as the basis and confirmation for our patent applications to protect the biomarker concept.

Medicortex has completed a clinical proof-of-concept trial in collaboration with Turku University Hospital (Tyks). Samples from 12 TBI patients and 12 healthy volunteers were collected and analyzed for the presence and for the level of the biomarker in state-of-the-art laboratories. The study demonstrated the diagnostic potential of the new biomarker in humans and it confirmed the prior preclinical findings. This was a significant milestone for Medicortex.

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Blood Biomarkers Signal Multiple Organ Dysfunction Syndrome After Critical Injuries

MedicalResearch.com Interview with:

Dr. Joanna Shepherd Centre for Trauma Sciences Blizard Institute Queen Mary, University of London

Dr. Shepherd

Dr. Joanna Shepherd
Centre for Trauma Sciences
Blizard Institute
Queen Mary, University of London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recent advances in resuscitation and treatment of life-threatening critical injuries means that patients with previously unsurvivable injuries are now surviving to reach hospital.  However, many of these patients develop Multiple Organ Dysfunction Syndrome (MODS), which is a failure of several organs including the lung, heart, kidney, and liver.

We studied immune cell genes in the blood of critically injured patients within the first few minutes to hours after injury, a period called the ‘hyperacute window’. We found a small and specific response to critical injury during this window that then evolved into a widespread immune reaction by 24 hours.  The development of MODS was linked to changes in the hyperacute window, with central roles for innate immune cells (including natural killer cells and neutrophils) and biological pathways associated with cell death and survival.  By 24 hours after injury, there was widespread immune activation present in all critically injured patients, but the MODS signal had either reversed or disappeared.

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An Ultra-Early Inflammatory Biomarker of Traumatic Brain Injury

MedicalResearch.com Interview with:

Dr Lisa J Hill PhD Institute of Inflammation and Ageing Research Fellow Neuroscience and Ophthalmology Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham UK

Dr. Hill

Dr Lisa J Hill PhD
Institute of Inflammation and Ageing
Research Fellow
Neuroscience and Ophthalmology
Institute of Inflammation and Ageing
College of Medical and Dental Sciences
University of Birmingham UK 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Traumatic brain injury (TBI) is the leading cause of death and disability among young adults and, according to the World Health Organization, by 2020 TBI will become the world’s leading cause of neurological disability across all age groups.  Early and correct diagnosis of traumatic brain injury is one of the most challenging aspects faced by clinicians. Being able to detect compounds in the blood that help to determine how severe the brain injury is would be of great benefit to patients and aid in their treatment.  Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins.  The discovery of reliable biomarkers for the management of TBI would improve clinical interventions.

We collected blood samples from 30 injured patients within the first hour of injury prior to the patient arriving at hospital and analysed them. Analysis of protein biomarkers from blood taken within the first hour of injury has never been carried out until now. We used a panel of 92 inflammation-associated human proteins when analysing the blood samples. The analysis identified three inflammatory proteins, known as CST5AXIN1 and TRAIL, as novel biomarkers of TBI.

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Circulating Cell Scoring System Identifies High Risk Prostate Cancer

MedicalResearch.com Interview with:

Dr. Yong-Jie Lu Reader in Medical Oncology Centre for Molecular Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary University of London John Vane Science Centre, Charterhouse Square, LONDON

Dr. Yong-Jie Lu

Dr. Yong-Jie Lu MBBS, MD, PhD
Reader in Medical Oncology
Centre for Molecular Oncology
Barts Cancer Institute – a CR-UK Centre of Excellence
Queen Mary University of London
John Vane Science Centre, Charterhouse Square
London

MedicalResearch.com: What is the background for this study?

Response: Identifying/monitoring the occurrence of metastasis and the prediction of the length that a patient may survive with a prostate cancer is critical for doctors to select the proper treatment, aiming to achieve the best control of the cancer with a balance of quality of life. Currently this is achieved mainly by analysing the cancer tissues acquired through very invasive procedures or by expensive imaging techniques, most of which expose the patient to toxic radioactive materials.

Circulating tumour cells (CTCs), which play a key role in the metastasis process, have been shown for their potential to be used for cancer prognosis by a simple blood sample analysis. However, previous CTC studies mainly detect the epithelial type of CTCs. Using the ParsortixTM (ANGLE plc) cell-size and deformability based CTC isolation system, we analysed not only epithelial CTCs, but also CTCs with epithelial-mesenchymal transition (EMT), a cellular process associated with cancer invasion and metastasis.

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Cholesterol Uptake Capacity, a New Indicator of HDL Functionality, for Cardiovascular Risk Stratification in the Real World.

MedicalResearch.com Interview with:
Amane Harada, PhD
Senior Researcher
Central Research Laboratories, Sysmex Corporation
Kobe, Japan

Ryuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of MedicineRyuji Toh, MD, PhD
Associate Professor
Division of Evidence-based Laboratory Medicine
Kobe University Graduate School of Medicine
Kobe, Japan 


MedicalResearch.com: What is the background for this study?

Response: High-density lipoprotein (HDL) exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative functions as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become “dysfunctional” HDL under pathological conditions.

Recent studies have demonstrated that cholesterol efflux capacity of HDL is a better predictor of CVD than HDL-C, suggesting that not only the quantity, but also the quality of HDL may significantly modulate and predict the progression of cardiovascular disease.

However, the conventional procedure for efflux capacity assay requires radiolabeling and cells, and the procedures are time consuming. Therefore, its clinical application is impractical.

To solve those problems, we have recently developed a new assay system to evaluate the capacity of HDL to accept cholesterol, named “uptake capacity”.

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Vascular Biomarker Predicts Death or Pulmonary Morbidity in Premature Infants

MedicalResearch.com Interview with:

Jegen Kandasamy MD Division of Neonatology Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program University of Alabama at Birmingham Birmingham, Alabama

Dr. Kandasamy

Jegen Kandasamy MD
Division of Neonatology
Assistant Professor/Director, Rare Disease Program and Congenital Anomalies Program
University of Alabama at Birmingham
Birmingham, Alabama 

MedicalResearch.com: What is the background for this study?

Response: Preterm infants, especially those that are born with a birth weight of 750 grams or less, are prone to a lung disease called bronchopulmonary dysplasia (BPD) because the development of lungs in these infants takes place in an environment that has more oxygen than that available in utero. Recently, pulmonary blood vessel growth and function has been hypothesized to play a causal role in the pathogenesis of BPD. Vascular endothelial cell function has been shown to affect hyperoxia-induced lung damage in animal studies. An important source of human vascular endothelial cells is the umbilical cord of newborn infants. These human umbilical venous endothelial cells (HUVEC) have been used to measure endothelial cell function in various diseases but never in diseases related to the newborn infants from whom they were derived.

In addition, the mitochondria in various cells in our body respond to oxygen toxicity by creating, as well as consuming, reactive oxygen species (ROS) that mediate most of the effects of oxygen-induced damage. Therefore, we designed this study to measure mitochondrial function in vascular endothelial cells obtained from the umbilical cords of prematurely born infants at the time of their birth. We then compared these mitochondrial functional measures between infants who later died or developed BPD versus those who survived without BPD.

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New Prostate Cancer Specific Assay May Reduce Need For Biopsies

MedicalResearch.com Interview with:

Eric A. Klein, MD</strong> Chairman, Glickman Urological and Kidney Institute Cleveland Clinic

Dr. Klein

Eric A. Klein, MD
Chairman, Glickman Urological and Kidney Institute
Cleveland Clinic

MedicalResearch.com: Which of these results did you find most interesting or surprising?

Response: What’s most interesting is that the IsoPSA assay redefines how PSA is measured, which links it more closely to the underlying biology of cancer. Current assays measure only the concentration of PSA, which can be affected by conditions other than cancer – BPH most commonly, but also infection and inflammation – which limits its diagnostic accuracy for finding cancer. Its been known for several decades that PSA exists in multiple different forms in the bloodstream in patients with prostate cancer.

These novel molecules arise because cancer cells have deranged cellular metabolism that result in the generation of new species of PSA, making their measurement more tightly linked to the presence or absence of cancer and even the presence of high grade cancer (where cellular metabolism is even more disordered).

The IsoPSA assay is the first assay to measure all of these isoforms and thus has better diagnostic accuracy for cancer.

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TeloView Measures Genomic Stability To Predict Disease Aggressiveness

MedicalResearch.com Interview with:

3D SignaturesJason Flowerday, CEO
Director of 3D Signatures 

MedicalResearch.com: What is the background for 3D Signatures?

Response: 3D Signatures, and its clinical lab tests, which incorporate its proprietary TeloViewTM software analytics, is the culmination of over 20 years of ground-breaking research conducted by Dr. Sabine Mai and her colleagues. It is the only technology in the world that quantifies genomic instability, which is the hallmark of cancer and other proliferative diseases at the whole-cell level.

By measuring the degree of genomic instability from different tissues, TeloViewTM has produced clinically actionable distinctions in the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is well developed and supported by 22 clinical studies on over 2,000 patients on 13 different cancers including Alzheimer’s disease. The results have been exceptional and represent a universal biomarker platform across all disease areas that the company has investigated to date.

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Saliva Test Can Predict Concussion Duration in Children

MedicalResearch.com Interview with:

Steven Daniel Hicks, MD, PhD Assistant Professor, Division of Academic General Pediatrics College of Medicine Penn State Health

Dr. Hicks

Steven Daniel Hicks, MD, PhD
Assistant Professor, Division of Academic General Pediatrics
College of Medicine
Penn State Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are about 3 million concussions in the US each year and the majority occur in children. Parents of children with concussions commonly cite length of recovery as a major concern, but pediatricians have no objective or accurate tests for addressing this concern.

Our research group previously identified small regulatory molecules called microRNAs that were altered in both the spinal fluid and saliva in children with traumatic brain injuries. In this study we investigated whether those microRNAs could predict duration of concussion symptoms. In 52 children with concussion we found a set of microRNAs that predict whether concussion symptoms would last beyond one month with over 80% accuracy. This was significantly more accurate than survey based tools such as the sports concussion assessment tool or a modified concussion clinical risk score. Interestingly, the microRNAs with predictive accuracy targeted pathways involved in brain repair and showed correlations with specific concussion symptoms.

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Granzyme B Probe Plus PET Scanning Helps Determine Response To Immunotherapy

MedicalResearch.com Interview with:

Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School

Dr. Ben Larimer

Ben Larimer, PhD research fellow in lab of
Umar Mahmood, MD, PhD

Massachusetts General Hospital
Professor, Radiology, Harvard Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:
Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies.

The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively.

Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B.

We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow.

We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.

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