The diagnostic blood test being developed is intended to speed treatment critical to improving  ischemic stroke outcomes

Stroke survivor Lauren Barnathan was one of the first patients to donate a blood sample for the pilot study of a stroke diagnostic test under development by VuEssence Inc and USF Health Neurology.

Lauren Barnathan, who routinely works with stroke patients as a speech pathologist at Tampa General Hospital, is athletic, maintains a healthy diet, and meditates.

And in January 2018, at age 30, she suffered a life-threatening stroke. A tear in the right carotid artery in her neck led to blood clot that dislodged, blocking blood flow to part of her brain.

Barnathan was among the first patients to donate a blood sample for a pilot-feasibility study teaming USF Health Neurology with VuEssence Inc., a Tampa Bay area medical device company with a laboratory based in the USF Research Park.  The ongoing study aims to develop a blood test that can accurately and rapidly detect when a person is having an acute ischemic stroke based on measurable biomarkers in the blood – and, ultimately, help guide treatment decisions for better outcomes.

“On the night of my stroke, when they were consenting me to be part of the study in the emergency department, I remember thinking how great it would be to have a test like that,” said Barnathan, whose fiancé Adam Barnathan, an ER medicine physician (now her husband), called 911 as soon he saw symptoms: facial droop and an inability to use one side of her body. Her timely and successful treatment at the TGH Comprehensive Stroke Center included the blood clot-dissolving drug tPA and a minimally-invasive procedure (mechanical thrombectomy) to physically retrieve a clot from the vessel blocked in her brain.

W. Scott Burgin, MD, professor and division chief of vascular neurology at USF Health Morsani College  of Medicine, leads the Comprehensive Stroke Center based at Tampa General Hospital.

A potential “game changer” for stroke neurology

No reliable early-detection test exists to identify a stroke – the fifth most common cause of death and the leading cause of long-term disability in the U.S.  Most strokes are ischemic, meaning that blood flow to the brain is obstructed by a clot in an artery. Once deprived of oxygen-rich blood, brain cells begin dying. And, stroke outcomes – including recovering the ability to walk, speak, see, understand, reason and/or remember — are generally worse the longer treatment is delayed.

“When I look at all the things that could change the way I’ve practiced stroke neurology all these years, this new diagnostic test would be one of the biggest game changers,” said W. Scott Burgin, MD, professor and division chief of vascular neurology at USF Health and director of its Comprehensive Stroke Center based at TGH.

A one-hour delay in treating stroke equals more than 450 miles of nerves cells, the approximate distance from Tampa to Atlanta, Dr. Burgin said. “And that’s a lot of brain tissue lost. So, any technology that can improve our ability to diagnose accurately and quickly would likely translate into a huge improvement in patients’ functional outcomes.”

USF engineering alumna Maha Sallam, PhD, is president and founder of VuEssence Inc., a Tampa Bay medical device company

Dr. Burgin (a clinical advisor to VuEssence) has been consulting with Maha Sallam, PhD, president and founder of VuEssence, on development of the early-detection stroke test. This applied research project between the university and industry partner VuEssence is funded in part by a Florida High-Tech Corridor Matching Grant, which supports stroke investigator efforts, scientific input into trial design and administration, and study logistics.

So far, about 200 blood samples have been collected for analysis from consenting patients who arrive at TGH’s emergency department with a suspected stroke, and the researchers plan to collect 200 more.

Doctors currently use clinical assessment, including a physical examination and obtaining a medical history, and brain imaging with MRIs and CT scans to assist with stroke diagnosis. Combined with ambulance transport to the hospital ER, these standard diagnostic methods can take hours, increasing the risk of serious brain injury.

“Getting someone treated within a short time period can be complex.” Dr. Burgin said.

Adding stroke-specific gene expression to diagnostic arsenal

Other diseases, such as low or high blood sugar, epilepsy, or migraines affecting one side of the head, can mimic stroke – and may need to be ruled out before specialized treatment by a multidisciplinary stroke team begins. And in the earliest stages of stroke, Dr. Burgin said, CT scans of the brain often appear essentially normal.

Blood samples are analyzed for stroke-specific gene expression at the VuEssence laboratory in USF’s Research Park.

“Right now, physicians really don’t know how the underlying biology in the body, the gene expression, is changing for a particular patient exhibiting acute stroke symptoms,” said Sallam, a USF graduate with a doctorate in computer engineering. “We hope to add that avenue of new information to existing diagnostic tools.”

VuEssence scientists analyze blood samples for specific products made by genes (gene expression) in response to the trauma happening in cells during stroke onset. Such genetic information may help doctors detect a stroke versus a condition that mimics stroke. The technology may also help differentiate the type of ischemic stroke – for example, indicate high probability of emergent large vessel occlusion that could benefit from a mechanical thrombectomy to remove the clot.

The company continues to reduce the time required to identify stroke-specific gene expression in the blood, with promising preliminary results, Sallam said. “Our goal is to get the system to process the patient’s blood (for stroke detection), so that critical test results are available less than 15 minutes” from the time blood is drawn.

To speed stroke treatment, diagnostic test results need to be available soon after a patient arrives at the hospital – if possible, even before.

Blood is collected from consenting patients who arrive at Tampa General’s emergency department with symptoms indicating high likelihood of stroke.

Long-term goal: Portable test device on ambulances

Both Sallam and Dr. Burgin agree that, ideally, the diagnostic blood test would be incorporated into an easy-to-use, portable device that paramedics and other first-responders could carry for pre-hospital detection and differentiation of strokes.

That would provide emergency medical services a much-needed tool to identify individuals with likely severe strokes, so those patients can be directly transported to the closest facility equipped for immediate endovascular therapy, Dr. Burgin said.

“If we get the test to work, the (long-term) goal would be to make it universally available on ambulances, whether in rural Montana or New York City,” he said. “In Montana, getting a patient to a specialized stroke center can be a significant endeavor. But, if the patient’s dizziness is caused by a stroke mimic, such as low blood sugar, they can probably go to the nearest hospital.”

First, though, VuEssense is focused on developing a streamlined test to be FDA approved and implemented in hospital settings and emergency departments, Sallam said. “If all goes well,” she added, “it will take some time before the point-of-care diagnostic technology could be available in ambulances.”

***

This February, Barnathan finished her first half-marathon at the Gasparilla Distance Classic in Tampa.| Photo courtesy of Lauren Barnathan

Barnathan, who overcame mobility and balance challenges after hospitalization, made virtually a full recovery. She returned to work about a month after her stroke, danced at her wedding several months later, and this February ran her first half-marathon, the Gasparilla Distance Classic, with her husband.

But in her professional role she sees stroke survivors who have not been as fortunate.

“Anything that can help expedite the process of intervening to minimize stroke damage would be a huge win,” she said.

Dr. Burgin with Tara McTigue, research nurse in the USF Health Department of Neurology

Dr. Sallam with Christy Larkins, PhD, a senior scientist at VuEssence

Lauren with her husband, Adam Barnathan, MD, an emergency medicine physician| Photo courtesy of Lauren Barnathan

-Photos by Allison Long, USF Health Communications and Marketing

The Byrd Alzheimer’s Institute is participating in a nationwide study looking at whether Medicare should cover the costly amyloid PET scan

TAMPA, FL (July 24, 2017) — Amyloid build-up in the brain is a crucial component of Alzheimer’s disease. A brain amyloid PET scan can detect the sticky plaque, signaling its severity. But most patients can’t afford it as the scan costs as much as $11,000 out of pocket.

The USF Health Byrd Alzheimer’s Institute is participating in the nationwide “Imaging Dementia-Evidence for Amyloid Scanning” (IDEAS) study. Researchers are investigating the significance of the amyloid-detecting PET scan to help determine if it should be covered by Medicare. That conclusion will be drawn by comparing the patient’s initial management plan to the one created based on data from the amyloid PET scan.

Dr. Amanda Smith leads clinical research in Alzheimer’s disease at USF Health.

Of the 4,000 IDEAS participants who’ve so far completed their 90-day follow-up, about 70 percent have had their management plans altered. This includes drug therapy, counseling and additional testing. The Byrd Alzheimer’s Institute reports having similar results in its 23 patients enrolled so far.

“Amyloid PET scanning has really revolutionized our ability to accurately diagnose Alzheimer’s disease,” said Amanda Smith, MD, medical director of the USF Health Byrd Alzheimer’s Institute. “Our hope is that by demonstrating how these scans impact doctors’ decision-making, we can show how they save insurance dollars in the long run, and have them become part of the standard medical workup for dementia.”

Byrd Alzheimer’s Institute is enrolling additional participants who are existing patients. IDEAS intends to enroll 18,000 Medicare beneficiaries with mild cognitive impairment. The study is intended to prove early diagnosis will provide patients more accurate drug treatment plans and reduce unnecessary hospitalizations. 

 *Preliminary results were presented at the 2017 Alzheimer’s Association International Conference in London.

David Morgan plays a leading role in an ambitious national research movement to help stop Alzheimer’s disease by 2025

In a year’s time Alzheimer’s disease affects more Americans than cancer and heart disease, the country’s top two causes of death. And, according to a report by the Rand Corporation, the total economic costs of dementia – from $159 billion to $215 billion yearly — slightly surpass those of heart disease and exceed cancer care costs by 30 percent.  Yet, the federal government spends five times more on heart disease research than on Alzheimer’s research and eight times more on cancer research.

That’s why in addition to his roles as a senior administrator and researcher, David Morgan, PhD, chief executive officer of the USF Health Byrd Alzheimer’s Institute, dedicates time advocating for more Alzheimer’s research funding at the national and state levels. Dr. Morgan, is a founding member and lead representative of the ResearchersAgainstAlzheimer’s, a coalition focusing the energies of the research community on the aggressive goal of stopping Alzheimer’s by 2025.

David Morgan, PhD

  Listen to Dr. Morgan audio clip below.

“The major risk factor for Alzheimer’s disease is old age,” said Dr. Morgan, distinguished professor of molecular pharmacology and physiology at the Morsani College of Medicine. “As we see gains in longevity, due largely to success in treating other diseases, and as more baby boomers pass age 65, the financial impact of Alzheimer’s and related dementias on Medicare will overwhelm our country’s capacity to maintain the program.”

Dr. Morgan remains optimistic that translational research conducted in the laboratories and clinics at the Institute can contribute to discoveries leading to two things by 2025:  the tools to prevent Alzheimer’s in high-risk older adults not yet showing symptoms, and treatments to effectively slow progression of the memory-robbing neurodegenerative disease in those diagnosed.

“We don’t need breakthroughs to achieve these two goals. We need the public and private resources to do the hard work of proving the science is right,” Dr. Morgan said. “Without the investment, we won’t get there.”

Leading a translational center at forefront of Alzheimer’s research and care

During Dr. Morgan’s tenure, the Byrd Alzheimer’s Institute – combining laboratory research, patient clinics, drug trials, and caregiver/health professional/first responder education under one roof — continues to grow and strengthen.

When he was tapped to lead the Institute in 2009, four doctoral researchers occupied less than 30 percent of the partially shelled, seven-floor facility.  Today, nearly 30 basic science and clinical faculty members, primarily from the Morsani College of Medicine, have appointments at the translational research center, bolstered by another dozen associate members from across USF. The building is nearly fully built out and occupied.

Under Dr. Morgan’s leadership, the USF Health Byrd Alzheimer’s Institute – a translational research center at the forefront of Alzheimer’s disease research and care — continues to grow and strengthen.

Despite intense competition for reduced research funding, Byrd Institute investigators attracted more than $7.5 million in new research grants and contracts last fiscal year, largely from the National Institutes of Health (NIH) and private foundations. New and ongoing research focuses on understanding the pathophysiology of Alzheimer’s as well as testing whether treatments targeting amyloid (plaques) or tau (tangles) in the brain can halt or slow progression of the disease itself, not just alleviate some symptoms.

“In the first six months I directed this Institute I learned more about the clinical aspects of Alzheimer’s disease than I had in the 20 preceding years,” Dr. Morgan said. “Having physicians who see patients and conduct clinical studies in the same building helps motivate scientists working in the laboratories.  It greatly facilitates the rate at which the laboratory research findings are tested in the clinic.”

Harnessing the power of advanced brain imaging techniques for clinical research

One of Dr. Morgan’s early strategic decisions was to invest in a state-of-the-art positron emission tomography (PET) scanner.  The addition has begun to pay off with a steady increase in patients referred to the Institute’s PET imaging center for brain and oncology diagnostic services. In addition, more clinical studies funded by the NIH and pharmaceutical companies are using an FDA-approved amyloid imaging agent to detect and measure amyloid, a hallmark feature of Alzheimer’s in the brain.  Scientists now know that amyloid plaques begin building up in the brain years before the first signs of memory loss.

USF is home to one of few Alzheimer’s centers in the country to own a PET scanner, which is used with neuroimaging agents in studies looking to detect signs of Alzheimer’s in the brain before symptoms are displayed. Dr. Morgan, left, with Amanda Smith, MD, the Institute’s medical director, who oversees clinical trials supported by the NIH and pharmaceutical industry.

The Institute expects to be among the 200 sites participating in the recently announced national Imaging Dementia – Evidence for Amyloid Scanning (IDEAS) study to determine the clinical usefulness of amyloid PET scans in helping doctors accurately diagnose Alzheimer’s and other dementias in cases where the cause of cognitive impairment is uncertain. Dr. Morgan is optimistic that the comprehensive study will demonstrate the value of amyloid imaging and advance Medicare and other insurance carriers toward its reimbursement.

“As we run trials evaluating drugs to see if they can reduce amyloid or tau buildup in the brain, we can monitor how much is there before and after and determine if (the investigational therapy) hit the target,” Dr. Morgan said. “It is a very important biomarker for progression of the disease.”

He looks forward to the day when physicians will be able to use advanced brain imaging techniques to screen for Alzheimer’s much like they do now for heart disease, so that intervention can be started early before cell death in the brain becomes irreversible.

Merging interests in memory and age-related brain changes to tackle Alzheimer’s

Dr. Morgan’s 35-year career in neurosciences started at Northwestern University where he did his doctoral research on the neurochemistry of learning and memory. As a postdoctoral fellow at the University of Southern California School of Gerontology in the early 1980s, he investigated age-related changes in the brains of rodents and humans. During that period momentum began building for federal efforts to combat Alzheimer’s disease and researchers discovered a new cerebrovascular protein, beta amyloid, identified as a pathological hallmark of Alzheimer’s disease and prime suspect in triggering nerve cell damage.  Dr. Morgan seized the opportunity to apply his background in aging and brain function on finding drugs to treat Alzheimer’s dementia.

Dr. Morgan worked with colleagues at USF to develop a mouse genetically modified to develop Alzheimer’s symptoms early in life. He is an expert in using transgenic mouse models to test new immune therapies against both amyloid and tau — both considered pathological hallmarks of Alzheimer’s disease.

Arriving at USF in 1992, he collaborated with colleagues to create a mouse genetically modified to develop Alzheimer’s symptoms early in life (the APP+PS1 mouse model of Alzheimer’s disease).  Dr. Morgan’s impressive research portfolio includes studies to help determine how inflammation in the brain affects the Alzheimer’s disease process and to test gene therapy and immune therapy against the amyloid peptide. He currently leads a four-year, $1.75-million R01 grant from the National Institute of Neurological Disorders and Stroke, exploring antibodies to protect against the accumulation of neuron-killing tau tangles in a transgenic mouse model.

Dr. Morgan’s work has been published in many high-impact journals including Science, Nature and the Journal of Neuroscience, and he has consulted with both major pharmaceutical companies and small biotechnology firms on the development of Alzheimer’s therapeutics.

Dr. Morgan shares laboratory space at the Institute with senior scientist Marcia Gordon, PhD, professor of molecular pharmacology and physiology; Daniel Lee, PhD, and Maj-Linda Salenica, PhD, both assistant professors of pharmaceutical sciences; and Kevin Nash, PhD, assistant professor of molecular pharmacology and physiology. While he continues to seek out new research – he and Dr. Nash are teaming up to find ways to enhance anti-inflammatory activity of the protein fractalkine in the brain — lately he spends as much time mentoring junior faculty.

“I’ve reached a point in my career where I feel it’s critically important to help junior faculty improve the grant proposals they write so they can build their own track records as principal investigators,” Dr. Morgan said.

Early in his scientific career, Dr. Morgan seized the opportunity to apply his background in aging and brain function on finding drugs to treat Alzheimer’s dementia.

Building upon scientific discoveries to find effective treatments

The search for answers about the cause of Alzheimer’s has spanned many theories in the last several decades.

“There’s a broad consensus among most researchers today that a combination of amyloid and tau is needed to cause Alzheimer’s disease.  Amyloid alone is not enough,” Dr. Morgan said. “The accumulation of amyloid outside neurons may trigger abnormal inflammation in the brain, which in turn causes tau tangles to build up inside the neurons and that leads to neuron death.”

The exact cascade of events and amount of plaques and tangles resulting in full-blown Alzheimer’s pathology is still unknown, he added, and no doubt complex.

Dr. Morgan, who holds an undergraduate degree in philosophy, is philosophical about what the USF Health Byrd Alzheimer’s Institute is working toward under his leadership.

“I’m not coming to work because I think we’re going be awarded a patent for a drug that cures Alzheimer’s disease,” he said. “But I am confident that the things we discover at USF, when integrated with the larger community of scientific knowledge, will move us closer to a better understanding of this devastating neurodegenerative disease and result in meaningful treatments to benefit patients and their families.”

In addition to his roles as senior administrator, scientist and mentor, Dr. Morgan advocates for more Alzheimer’s research funding at the national and state levels.

Amyvid is the first and only FDA-approved diagnostic PET tracer for imaging beta amyloid plaques in the living brain

Tampa, FL – (Sept. 5, 2012) The USF Health Byrd Alzheimer’s Institute’s Eric Pfeiffer Imaging Center is one of only a limited number of PET imaging sites in Florida to offer Amyvid brain imaging.  Amyvid is a diagnostic PET (positron emission tomography) tracer to detect the presence or absence in the brain of significant amyloid plaques, a hallmark of Alzheimer’s disease, while patients are still alive.  The radiotracer allows physicians to see evidence of amyloid plaques in patients with cognitive impairment when providing clinical evaluation for Alzheimer’s disease and other causes of cognitive decline.

Alzheimer’s disease (AD) is one of many possible causes of dementia or cognitive impairment. Patients with symptoms of cognitive impairment can be misdiagnosed with Alzheimer’s disease, and up to one in five patients without AD pathology upon autopsy are clinically diagnosed with the neurodegenerative disease. In conjunction with clinical assessment, an imaging test or brain scan could detect the presence of neuritic, beta-amyloid plaques in the living brain.

An Amyvid PET scan is intended for use in adult patients with early stage dementia or memory problems. Amyvid is injected into the blood stream, where it binds to amyloid plaques in the living brain. An Amyvid PET scan is not a covered service under Medicare. For questions on payment and scheduling for Amyvid PET imaging, call (813) 396-0728.

 For more information about Amyvid, visit www.amyvid.com

 -USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities.

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