Construction of a new oversized vehicle tunnel and premium RV infield parking section at Talladega Superspeedway is still on schedule to be completed in time for the April NASCAR race, despite large amounts of rainfall and unusual groundwater conditions underneath the track.
Track Chairman Grant Lynch, during a news conference Wednesday at the track, said he’s amazed the general contractor, Taylor Corporation of Oxford, has been able to keep the project on schedule.
“The amount of water they have pumped out of that and the extra engineering they did from the original design, basically to keep that tunnel from floating up out of the earth, was remarkable,” Lynch said.
Alabama’s auto workers built nearly 1.6 million engines last year, as the state industry continues to carve out a place in global markets with innovative, high-performance parts, systems and finished vehicles.
Last year also saw major new developments in engine manufacturing among the state’s key players, and more advanced infrastructure is on the way in the coming year.
Hyundai expects to complete a key addition to its engine operations in Montgomery during the first half of 2019, while Honda continues to reap the benefits of a cutting-edge Alabama engine line installed several years ago.
"Frontier Airlines will begin direct flights from Birmingham-Shuttlesworth International Airport on April 11, the airline announced today. Frontier Airlines will start by offering direct service to Denver, Orlando and Philadelphia from Birmingham. Introductory prices will start at $39."
"At 87, Clint Eastwood is not only trying new things, he’s trying daring new things, and his new film 15:17 to Paris represents one of the most audacious gambits of his career. To dramatize the tale of three Americans who tackled and subdued a heavily armed Islamist terrorist on a train out of Amsterdam in 2015, Eastwood cast the young men, none of whom had professional acting experience, as themselves. It’s a decision with little precedent in the entire history of motion pictures."
“With the establishment of this center, UAB Medicine has again brought one of the latest, most advanced medical technologies to our region,” said Will Ferniany, Ph.D., CEO of the UAB Health System. “Proton therapy will be a valuable tool that our physicians and scientists in the Department of Radiation Oncology, School of Medicine and the O’Neal Comprehensive Cancer Center can employ to the betterment of thousands of cancer patients in Alabama and the surrounding area.”
Proton therapy uses an aimed beam of protons directed at the tumor site. The beam is configured to deliver the majority of its energy precisely at the tumor location. Healthy tissue in front of the tumor receives a minimal amount of energy, and tissue behind the tumor receives very little. This reduces the damage to healthy tissue that is common in the use of conventional X-ray radiation and is the cause of most side effects.
“Opening the center is an important milestone for the residents of Alabama who now have access to proton therapy closer to home,” said Chris Chandler, CEO of Proton International. “Our mission is to work in partnership with leading clinical entities such as UAB so patients and families do not have to travel long distances and suffer further cost and stress at such a critical time.”
UAB physicians anticipate beginning consultations with prospective patients in the next two weeks, with the first proton therapy treatments taking place at the end of February.
Proton therapy is used to treat tumors of the brain and central nervous system, spine, head and neck, lung, prostate, liver, gastrointestinal tract and colon, and some breast tumors. While it treats primarily single-site tumors, in some cases it can be used for treating cancer that has spread, or metastasized, to surrounding tissue because of its focused dose capabilities.
“Proton therapy will allow us to treat deep-seeded cancers,” said James A. Bonner, M.D., the Merle M. Salter Endowed Professor and chair of the UAB Department of Radiation Oncology. “It can be particularly efficacious in the treatment of children, who can be highly sensitive to the effects of radiation therapy. We are excited to offer this cutting-edge approach for patients and families in Birmingham, across Alabama and beyond.”
Proton International at UAB is on 20th Street South between Fourth and Fifth avenues. The facility consists of a three-story building to house clinical exam rooms, offices and the ProBeam proton therapy system, manufactured by Varian Medical Systems, a longtime partner with UAB in the delivery of radiation therapy. The medical staff, including radiation oncologists, medical physicists, dosimetrists, radiation therapy technologists and nurses, will be exclusively from UAB.
The heart of proton therapy is a machine called a cyclotron, which produces the proton beam and delivers it to the precise location in the body to destroy tumor cells. Proton International at UAB’s cyclotron, nick-named Emma, was manufactured in Germany. The $25 million, 90-ton cyclotron was brought by ship to Brunswick, Georgia, then transported to UAB last March by a specialized truck, with 20 axles, 78 wheels, and drivers in front and back. A heavy-lift crane was assembled on Fourth Avenue South to lift and deposit Emma into the facility via the roof.
UAB will also be involved in clinical research studies on the use of proton therapy to discover the full utility of the therapy and produce best practice parameters on its use. Click here for a more detailed explanation of how proton therapy works.
Recovering UAB trauma patient with eye toward naval career vows to ‘help others’
On May 24, 2018, Cole Burton stood along a road cut through the heart of Red Mountain in Birmingham. He and his fellow students from an Auburn University geology class were studying formations in the rock exposed when the road was dug.
Burton took a moment to gaze to the north, over the sprawling campus of the University of Alabama at Birmingham in the valley below. His eyes settled on the buildings of UAB Hospital. Little did he know that, in just a few short hours, he would be offloaded from a helicopter on the hospital rooftop, clinging to life.
Following their Red Mountain investigations, the class proceeded to Glencoe, near Gadsden.
“We were walking on the side of the road,” Burton recalled. “My friend Nick Hood and I were both hit by an impaired driver who may have overcorrected and lost control of their vehicle.”
Both were airlifted to the UAB Trauma Center. Burton had a traumatic brain injury (TBI), broken bones, bruised lungs and a tear in his small intestine that required emergency surgery.
“The TBI and the intestinal tear were life-threatening injuries,” said Parker Hu, M.D., the UAB trauma surgeon who spearheaded Burton’s care. “He was comatose upon arrival here and placed on mechanical ventilation.”
Hood, unfortunately, did not survive. UAB physicians were not sure Burton would, either.
“Brain injuries are hard to predict,” Hu said. “Most of the time, people with the kinds of injuries Cole had sustained never wake up, or they wake up different. Some have physical or cognitive impairment, or their personalities change. A large part of his recovery was the question of whether he would wake up or not.”
Hu and the other UAB surgeons from the Department of Neurosurgery who treated Burton were honest with the family, telling them the outlook was not good. Burton’s parents, Charlie and Tina, and his younger sister, Libba, understood. But they also understood Cole’s strength and will to live.
“We believe that, with God, all things are possible,” Charlie Burton said. “We asked the doctors to continue treating Cole as if recovery were likely, and we would continue to pray.”
“Being in intensive care is a roller-coaster ride,” Tina Burton said. “One step forward, then one step back. You get off a ventilator, then have a setback and go back on the vent. We understand that’s part of the process, but it’s difficult.”
The situation took a toll on the family. Charlie and Tina stayed at the ICU virtually nonstop. Libba, a freshman at Troy University, made sure they took care of themselves during the process.
“I was leaning into going into nursing already, and I guess that took over,” she recalled. “In a way, it was easier on me than it was on my parents. I tried to be the strong one, and the UAB nurses who took care of Cole and the rest of us inspired me to really want to be a nurse.”
Slowly, Burton responded. He came out of the coma on June 15, three weeks after the injury.
“While Cole’s prognosis was poor, we know that it’s possible for patients to have a full recovery,” Hu said. “For Cole to wake up and still be Cole was remarkable. We can’t predict which patient might have that kind of recovery; that’s why we do the best we can for every patient in our care.”
Relearning how to live
Coming out of the coma was not the end of Burton’s recovery. He had to relearn how to accomplish even simple tasks such as talking, walking and eating. On discharge from UAB just over a month after the injury, his family moved him to the Shepherd Center in Atlanta for rehabilitation.
Two months of inpatient, six months of outpatient and an additional six months of intense personalized physical therapy later, followed by a return to classes at Auburn, Burton came back to UAB for a visit – a visit that confirmed Hu’s statement that “Cole is still Cole.”
The whole Burton family came to the hospital just before Thanksgiving to reconnect with hospital staff and to say thank you to the physicians, nurses, therapists and all other hospital professionals who played a role in Burton’s recovery.
As Burton toured the emergency department, ICU and the UAB helipad, the casual observer would see no evidence that there had ever been a question of whether he would wake up.
“I set the bar high for myself,” Burton said. “I have long-term goals from before the injury that are still the same and short-term goals to help achieve them. Having a goal is very important for recovery.”
The long-term goal? A career as an officer in the U.S. Navy. Burton was, and still is, active in Navy ROTC at Auburn.
“I’m still actively working on rehab to pass the Navy physical fitness test,” Burton said. “I have to run a mile and a half in 12.5 minutes and do as many pushups and situps as I can in two minutes. I’m up to 60 pushups and 85 situps so far.”
Burton ran in the Peachtree 10K road race this summer. Last year, he watched from a wheelchair.
“The Navy has been patient, waiting on me to recover as completely as I can,” he said. “They will look at my overall fitness – academically, physically and socially – to see if I can serve.”
Burton is still working to regain complete function of his left hand, but is on pace to graduate from Auburn in December with a degree in geology. While a naval career is his first choice, Burton has a plan if that does not work out.
“I will find a way to give back in any way I can,” he said. “Use every breath I have to help others. Whether that’s in the Navy or not.”
“I don’t think there is any limit to his recovery,” Hu said. “He’s met every challenge and continues to surpass expectations. Cole personifies the reason that we work as hard as we can for all our patients. We know that patients can have great outcomes despite what look like insurmountable odds.”
“Throughout rehab, I always thought that I’d get back to where I was before; but now I think that was the wrong mindset,” Burton said. “Now I think that I will always be improving. I want to be better than I was before. If I do my best today, it won’t be my best tomorrow. The growth mindset is really important. And I think the staff at UAB helped make that mindset possible. I’m so thankful for my second chance at life.”
This story originally appeared on the University of Alabama at Birmingham’s UAB News website.
UAB part of landmark national trial to examine how exercise affects your body, down to your molecules
What happens at the molecular level after exercise? Scientists, physicians and clinical exercise specialists from across the country are embarking on a landmark National Institutes of Health effort to find out.
“Decades of scientific research have demonstrated numerous important health benefits of exercise, but the underlying mechanisms at the molecular level are largely unknown – which is why MoTrPAC is a very exciting and important discovery project,” said Marcas Bamman, Ph.D., professor in the UAB Department of Cell, Developmental and Integrative Biology in the School of Medicine and director of the UAB Center for Exercise Medicine.
Scientists worldwide will be able to use the MoTrPAC molecular maps to generate hypotheses for future investigations of exercise-induced health benefits. Ultimately the rich data sets may also improve the ability of specialists to prescribe exercise programs precisely tailored to each individual.
“We will undoubtedly find individual differences,” said Francis Collins, M.D., Ph.D., director of the National Institutes of Health. “What works for me might be very different than what works for someone else. We want to discover that.”
The study, funded by a $240 million program through the NIH Common Fund, will enroll 1,980 adults across 10 clinical sites and 300 children at one site. Along with UAB, sites are Ball State University, Muncie, Indiana; Duke University, Durham, North Carolina; East Carolina University, Greenville, North Carolina; AdventHealth, Orlando, Florida; the University of California, Irvine; the University of Pittsburgh; the University of Colorado, Denver; University of Texas Medical Branch at Galveston; Pennington Biomedical Research Center at Baton Rouge; and University of Texas Health Science Center at San Antonio.
Most of the study participants will be people who do not exercise regularly. They will be divided into three groups: 840 who will do endurance exercise; 840 who will do resistance exercise; and 300 who will not do either. Participants in both exercise groups will receive personal coaching.
The exercise groups will go through three one-hour training sessions per week for about 12 weeks.
There will also be a comparison group consisting of 300 people considered highly active or trained, meaning they have been consistently sticking to endurance training or resistance training for the past year or longer.
Scientists will assess participants’ cardiorespiratory function, muscular strength and body composition. Researchers will also collect blood, muscle and fat samples, monitor participants’ free-living physical-activity level using wearable devices, and complete participant-reported outcomes and health status by interviews and questionnaires.
UAB is leading a three-site MoTrPAC clinical center called the Exercise and Physical Activity Collaborative Team with AdventHealth and Ball State University.
“The Human Performance Laboratory at Ball State University is honored to partner with UAB and the Translational Research Institute at AdventHealth on this exciting opportunity to better understand the molecular underpinnings that drive exercise adaptations and lead to numerous health benefits,” said laboratory director Scott Trappe, Ph.D.
For more information on participating in MoTrPAC, the contact is Kristie Williams, clinical trials manager, UAB Center for Exercise Medicine, 205-996-0855 or email@example.com.
Neurosurgeon Kristen Riley was able to remove 90 percent of the tumor as it wrapped around the carotid artery. (Bob Shepard/UAB)
It took four months of detective work, but physicians at the University of Alabama at Birmingham found the rare cause of a woman’s medical issues. UAB’s joint pituitary disorders clinic, featuring the unusual combination of endocrinology and neurosurgery, identified and removed a pituitary tumor from Debra Nelson that had gone undiagnosed for more than six years.
“While pituitary tumors are fairly common, the kind Debra had is the exception, accounting for only about 1 percent of all pituitary tumors,” said Kristen Riley, M.D., a neurosurgeon in the UAB Department of Neurosurgery in the School of Medicine. “She had a TSH-secreting tumor, or thyroid stimulating hormone-secreting tumor.”
The pituitary gland is about the size of a black-eyed pea with a stem, Riley says. It is situated at the base of the brain, behind the bridge of the nose. It produces hormones that affect other glands or organs in the body, and it helps manage and control hormone production in those glands.
In Nelson’s case, the TSH-secreting tumor on her pituitary gland sent signals to her thyroid to over-produce its two hormones, triiodothyronine and thyroxine. These two hormones control the body’s metabolism and help regulate how every cell in the body uses energy. An overactive thyroid can lead to heart problems, increased appetite and metabolic issues. Nelson spent more than six years looking for answers, all the while at risk for a thyroid crisis, sometimes called a thyroid storm, which can be fatal.
“This is a difficult condition to diagnose,” Riley said. “It takes a multidisciplinary effort, with expertise from endocrinology as well as neurosurgery, which is why UAB is one of the few medical centers able to offer this type of clinic.”
Vaughan said Nelson’s local physician had appropriately ordered a number of tests, but the results that came back were confusing. For example, tests showed the level of one particular hormone to be elevated. Usually in that situation, a second hormone should test low. But in Nelson’s case, test results indicated elevated levels of both hormones.
“Her test results were very unusual, so we began the process of whittling down those potential causes,” Vaughan said. “It took about four months of medical detective work – conducting tests and trying different medications – until we were confident that the issue was a TSH-secreting tumor on the pituitary gland.”
The tumor turned out to be wrapped around the carotid artery, which supplies blood to the brain as it passes by the pituitary gland. That is a delicate surgery.
“Pituitary tumors often push against the optic nerve, leading to vision issues,” Riley said. “We were able to remove about 90 percent of the tumor without causing damage to either the carotid artery or the optic nerve. The reduction in TSH allowed her thyroid to return to normal hormone production.”
“It was the best outcome that we and Debra could have hoped for,” Vaughan said. “There are only about five to 10 places in the entire country where patients can see a neurosurgeon and endocrinologist on the same day, at the same time and in the same room. Working independently, this would have been very difficult to diagnose.”
“This was a complex case even for an institution as advanced as UAB,” Riley said. “This really highlights the kind of patient who needs to be seen at a pituitary clinic with multiple disciplines available.”
Riley said they will use sophisticated imaging to keep an eye on Nelson’s tumor to be sure it does not begin to grow again.
Nelson, who is a health care professional herself, is ecstatic.
“I was floored by the kindness I experienced at UAB,” she said. “The neuro-intensive care unit had the best nurses I’ve ever had. Dr. Vaughan’s nurse, Stacy Rouse, was outstanding. Drs. Riley and Vaughn were so diligent in working to find out what my issues were and figuring out a way to treat them.”
“Complex cases such as this are why it is challenging yet so rewarding to be a doctor,” Vaughan said.
This story originally appeared on the University of Alabama at Birmingham’s UAB News website.
Normally, babies are kept nice and warm. But if there are issues during labor or delivery that interrupt oxygen flow to the baby’s brain, that thinking gets reversed. That is when medical professionals say dramatically lowering the baby’s temperature – a process called induced therapeutic hypothermia – can be critical.
In some births, the flow of oxygen to the brain is compromised. The umbilical cord can become compressed, for example. Compromised oxygen intake can lead to neurologic and developmental problems for an infant that can be permanent. Cooling the baby into an induced state of hypothermia – 93 degrees Fahrenheit for 72 hours — can, in many cases, prevent or minimize that damage.
Critical Care Transport, a service of UAB Medicine at the University of Alabama at Birmingham, has added a device to its fleet of transport vehicles to provide “active cooling” of neonates during hospital transfers. CCT is a UAB service offering air and ground transport for the sickest patients in what is essentially a flying or rolling intensive care unit.
Studies in cardiac arrest patients have shown that the rapid, uncontrolled return of oxygen to the brain following a period of reduced oxygen intake has a detrimental effect. Inducing hypothermia moderates the brain’s need for oxygen, allowing time for it to heal and to better tolerate the gradual return of oxygen-carrying blood to the brain.
At a hospital like UAB, with its Regional Neonatal Intensive Care Unit, active cooling technology is readily available. The same equipment is not always found at small community hospitals. For best effect, cooling must be initiated within a window of four to six hours after birth. That’s where CCT comes in.
The service transported more than 400 babies last year for a variety of causes, including oxygen deprivation.
“When you add in travel time, that four- to six-hour window gets pretty small,” said Laura Lee Demmons, CCT director. “In order to achieve effective cooling during transport, we realized that we needed sophisticated equipment that was unlike the large cooling devices found in hospitals, but was small and portable so we could start active cooling as soon as possible,”
CCT’s new device is a cooling blanket, Tecotherm Neo, from Inspiration Healthcare. It is a water-filled blanket that circulates chilled water while wrapped around an infant, holding at a constant 93 degrees. The device monitors the infant’s temperature every two seconds and makes minute changes in the cooling fluid to ensure that the child’s temperature remains stable.
Active cooling, using a device such as the water-filled blanket, is a step up from passive cooling, which is the primary alternative in many community hospitals. Passive cooling involves basic actions such as not turning on heating units in warmers or isolettes.
“The blanket allows for rapid, controlled cooling to a precise temperature,” said Demmons. “Now, in a scenario where we get a call from a hospital hours away for transport, we know we can establish active cooling within the time frame needed for best results.”
CCT has been providing medical transports for more than 35 years and has transported more than 50,000 patients. The team employs a twin-engine Cessna Citation Bravo jet for long-distance transport and three ground units for regional and local moves.
“We implemented the capability in December and had our first infant candidate in January,” Demmons said. “Our transport crews and neonatologists are thrilled to know that they have it available for the infants of Alabama and beyond.”
UAB Hospital lauded for seventh year in a row as one of America’s great hospitals
UAB Hospital has been listed on Becker’s Hospital Review’s 2019 list of 100 Great Hospitals in America. UAB has earned this distinction every year since 2013 and is the only hospital in Alabama to make the annual list published by Becker’s Healthcare, a leading source of cutting-edge business and legal information for health care industry leaders.
According to Becker’s, the hospitals included on this list have been recognized nationally for excellence in clinical care, patient outcomes, and staff and physician satisfaction. These institutions are industry leaders that have achieved advanced accreditation and certification in several specialties. The list also includes industry innovators that have sparked trends in health care technology, hospital management and patient satisfaction.
Becker’s 100 Great Hospitals website describes UAB Hospital as a 1,157-bed institution associated with UAB Medicine. The health system’s UAB Callahan Eye Hospital was one of the first level 1 ocular trauma centers in the country, and is the only level 1 ocular trauma hospital in Alabama. Founded in 1945, the health system comprises five facilities and more than 1,000 physicians. UAB Hospital was recognized as top-performing in various specialties, such as rheumatology and cardiac surgery, by U.S. News & World Report in 2018-19.
“We are honored to be named as one of the great hospitals in America for the seventh consecutive year,” said Will Ferniany, Ph.D., CEO of the UAB Health System. “UAB is a national leader in research, clinical care and medical education, which are the building blocks of a truly outstanding hospital. Every person who touches UAB Medicine in any way can take pride in this designation.”
“Research funding is a barometer that helps measure all the variables that reflect the success of an academic research institution,” said Chris Brown, Ph.D., vice president for Research at UAB. “The top schools in research are also among the top facilities in health care. There is a correlation between funding and the retention and recruitment of top faculty and the brightest students. Research and the funding that supports it are the structural basis of any academic research institution.”
Within the School of Medicine, six departments ranked in the top 10 for NIH funding in their fields, led by the Department of Dermatology, which held the top spot as the most-funded dermatology department in the nation.
The Department of Ophthalmology and Visual Sciences ranked fifth, the Department of Biomedical Engineering ranked fifth and the Department of Obstetrics and Gynecology came in at ninth in the nation, as did the Department of Cell, Integrative and Developmental Biology. The Department of Anaesthesiology was 10th on the NIH funding list.
Six more SOM departments placed in the top 20. Both the Department of Urology and the Department of Pathology ranked 12th, followed by the Department of Genetics at 13th. The Departments of Medicine and Neurology were 17th on their respective lists, while the Department of Pediatrics came in at 18th.
The departments with the largest gains were Genetics, which jumped from 31st in 2017 to 13th in 2018, and Neurology, which jumped from 29th to 17th.
This story originally appeared on the University of Alabama at Birmingham’s UAB News website.
Momaya, one of the team physicians for UAB athletics, began thinking about spectator injuries after reading accounts of a young child struck by a foul ball at a professional baseball game. He realized that there was scant information on spectator injuries. A search of the scientific literature revealed that there had been no studies that documented spectator injuries.
“Without data, there is no way to judge if spectator injuries are becoming more or less prevalent,” Momaya said. “There is no way to determine if more aggressive safety measures are warranted. So, we set out to see what information we could find that would shed light on the subject of spectator injuries.”
Looking back to 2000, the team tracked 181 spectator injuries, with the vast majority – 123 – coming from automobile or motorcycle racing. Cycling experienced 25 injuries, cricket 12, baseball 10 and hockey eight. The team documented 62 fatal injuries; 38 from vehicle racing, 17 from cycling, four from hockey, two from baseball and a single fatal injury from cricket.
“Most of these injuries are ballistic in nature, meaning the spectator was struck by something from the playing area, such as a ball, puck or vehicle,” Momaya said. “There are also instances in sports such as cycling or basketball where a competitor might inadvertently leave the playing area and make contact with spectators.”
Momaya and colleagues are calling for a central database for recording the occurrence of injuries to spectators during sporting events. A database would provide the information needed to gauge whether spectator injuries were increasing or decreasing and could provide insight into whether protective measures instituted by sporting organizations were effective.
“For example, Major League Baseball recently increased the area covered by netting to reduce the risk of fans being struck by foul balls,” Momaya said. “Without a systematic way to record injuries, there is no way to measure whether that effort is sufficient or if netting should be extended.”
The research team says the findings point to some obvious measures that could be implemented, such as impenetrable barriers at racing events that prevent vehicles or crash debris from entering the spectator area. Increased use of netting at baseball stadiums and higher, transparent barriers in hockey arenas could prevent balls and pucks from striking fans.
“Cricket venues tend to lack protective netting and barriers, which places spectators at increased risk of injury from balls hit into the viewing area,” Momaya said. “Cricket venues should follow the changes implemented by Major League Baseball with extended netting to protect spectators from injuries with high-speed balls.”
The authors also noted that the majority of injuries at cycling events were caused by impacts between spectators and vehicles other than the competitor’s, including a publicity caravan, security motorcycle and a tanker truck. There were also instances in motor racing where support vehicles were involved in spectator injuries.
“This suggests that factors such as crowd control, event planning and staff training also play important roles in spectator safety,” Momaya said. “In addition to protecting spectators from injury due to the sport, attention should be given to all components of the event to ensure that sports fans can safely enjoy their experience.”
Momaya acknowledges that there are challenges to an international database, requiring the coordination of multiple governing bodies across multiple countries. Additionally, sporting organizations would need to agree on the threshold of what is considered an injury.
“There is a fine line between an enhanced fan experience on one hand balanced against spectator safety on the other,” Momaya said. “As a physician, I think safety is the top priority. We need to categorize these injuries and use that data to find tangible ways to protect fans without significant compromise to the viewing experience. Spectator injuries, be they life-ending or life-changing, have no place in sport.”
UAB researchers study why some people don’t suffer Alzheimer’s effects
Researchers believe that some people – perhaps 30 to 50 percent of the population – are resilient to the effects of Alzheimer’s disease. Understanding what makes these people resilient to the debilitating symptoms of dementia could be a key to developing ways to treat or cure the disease.
“These are people who develop the pathology of Alzheimer’s disease: the tangles of tau protein and the accumulation of amyloid protein in the brain,” said Jeremy Herskowitz, Ph.D., assistant professor in the University of Alabama atBirminghamDepartment of Neurology, School of Medicine. “But they don’t develop the symptoms of the disease and are resilient to its effects. If we can understand why this segment of the population is resilient, we might have a new target for slowing or preventing the disease in those who are not resilient.”
One factor might be the size and shape of brain structures called dendritic spines. In a paper published in October2017, Herskowitz showed that aging individuals who had amyloid and tau buildup but did not develop dementia had longer and more numerous dendritic spines than those who developed dementia. Dendritic spines are sub-units of neurons that act as connectors between neurons, enabling the exchange of information, known as synapses, to occur. This is the basis for memory and learning.
Using an innovative imaging system developed in Herskowitz’s lab, the researchers will examine the brains of 200 subjects from a tissue repository at Rush University who were resilient to dementia in life, but had significant amounts of amyloid and tau protein.
Herskowitz’s system uses novel, exclusive software to turn microscope photos of brain tissue into 3D images that allow researchers to look more fully at the shape and dimensions of the dendritic spines. The team will look for the presence of more numerous, larger spines, as well as attempt to see if they can find differences in the brain tissue that might explain why.
Neurons use long, thin dendritic spines to connect and communicate with other neurons. Longer spines may indicate resiliency to Alzheimer’s disease.“If we can figure out why these people don’t have dementia, we might take great strides at learning why others do have symptoms,” Herskowitz said.
The next step will involve researchers at Emory University who will conduct proteomic testing of the brain samples to see if they can identify changes in proteins found in the resilient brains.
“We will be able to look at each set of dendritic spines for changes or clues that might help explain resiliency, such as changes to proteins or enzymes within the brain,” Herskowitz said. “The next step will be to duplicate any changes we find in animal models and test key proteins or enzymes for immediate therapeutic potential.”
The researchers also have functional magnetic resonance imaging scans on their 200 subjects done at Rush University during the patients’ lifetimes. The teams will be able to compare changes seen at the cellular or molecular level to changes in brain function identified by the fMRI.
UAB has joined a national consortium of researchers on resiliency in Alzheimer’s disease sponsored by the National Institute on Aging. The consortium is part of the NIA Accelerating Medicines Partnership – Alzheimer’s Disease, a partnership among government, industry and nonprofit organizations that focuses on discovering novel, clinically relevant therapeutic targets and on developing biomarkers to help validate existing therapeutic targets.
According to the NIA, dementia, of which Alzheimer’s disease is the most common form, is estimated to affect 36 million people worldwide. This number is expected to rise to 115 million by 2050 unless an effective therapeutic is developed. The financial toll of dementia is already staggering: In the United States alone, the costs of caring for people over age 70 with dementia were estimated to be as high as $215 billion in 2010.
Co-investigators along with Herskowitz are Chris Gaiteri, Ph.D., assistant professor, Department of Neurology, Rush University School of Medicine; and Nicholas Seyfried, Ph.D., associate professor, Department of Biochemistry, Emory School of Medicine.
Parkinson’s disease, which affects nearly 1 million Americans and 10 million people worldwide, occurs when dopamine-producing neurons in the brain are damaged or die. The loss of dopamine leads to tremors, stiffness and trouble walking and balancing. There is currently no preventive treatment, or a cure. In most cases, the damage has been accumulating for decades before symptoms appear. But what if it were possible to get an early warning about trouble in the brain based on turmoil in the gut? Or, better yet, what if some simple tweaks to intestinal bacteria — the gut microbiome — could interrupt Parkinson’s progression in the first place?
The grant will allow UAB researchers to launch a major investigation into the role of the gut microbiome in Parkinson’s disease. The gut microbiome refers to the 100 trillion or so bacteria and other microbes that live in the human intestines. Their combined DNA is 100 times larger than the human genome, says Haydeh Payami, Ph.D., professor in the UAB School of MedicineDepartment of Neurology and John T. and Juanelle D. Strain Endowed Chair, who is the principal investigator for the study.
Gut check At this point, only a handful of studies have looked at the microbiome in Parkinson’s disease; Payami’s paper in the journal Movement Disorders, in 2017, was one of the first. This research has uncovered tantalizing clues that could explain a puzzling problem in Parkinson’s research. What we know about the role of genes and environment in Parkinson’s does not add up, according to Payami.
“Large patient studies have searched for genetic variations and environmental triggers shared by people who have Parkinson’s disease,” Payami said. “Dozens of genetic risk factors have been identified, but each only increases risk by a small amount. There is a significant link between exposure to pesticides and herbicides, as well as repeated head trauma, and Parkinson’s risk; but again, not all people who have a genetic susceptibility and are exposed to these factors get the disease. There has to be something more than genes and environment.”
That is where the microbiome comes in. In 2016, researchers at CalTech removed the gut microbiome from mice bred to exhibit Parkinson’s symptoms, and the symptoms improved. Then they transplanted microbes from human patients with Parkinson’s into the mice, and the symptoms returned.
The 2017 study from Payami and colleagues drew on the patients enrolled in the NeuroGenetics Research Consortium, which has one of the world’s largest datasets of Parkinson’s patient information. Payami is lead investigator for the consortium, which includes both genomic and environmental data. By collecting additional fecal samples from those patients, the researchers found that the types of bacteria in the guts of people with Parkinson’s differed significantly from healthy controls. The researchers also discovered that Parkinson’s medications were linked to changes in gut bacteria as well.
Why microbiome? “The microbiome metabolizes drugs,” Payami said. “It can turn harmless drugs toxic, and vice versa. Exposure to pesticides and insecticides may be mediated by the microbiome as well. And because the microbiome is easily modifiable, it could offer a way to predict, prevent and even treat Parkinson’s disease.”
There are several other intriguing lines of study pointing toward the microbiome. In a number of small studies, eradicating Helicobacter pylori infection in the gut of Parkinson’s patients increased the effectiveness of levodopa, the most commonly used Parkinson’s medication. Scandinavian studies (here and here) found a link between cutting the vagus nerve — a physical connection between the gut and the brain, which was sometimes severed to treat peptic ulcer — and a lower risk of Parkinson’s.
The microbiome connection is still only a hypothesis, Payami cautions, and there is unlikely to be a single cause for Parkinson’s found. Instead, there are probably many different routes that all end in the same outcome.
“There’s no question that the gut microbiome is changed in Parkinson’s disease,” she said. What isn’t clear is whether the microbiome is changed as a consequence of the disease, or whether it contributes to the disease process itself. The same is true of drug-microbiome interactions: Could the makeup of a patient’s microbiome affect his or her response to treatment, or do medications alter the microbiome?
Payami suggests that the answer is all of the above. If so, it could be possible to manipulate the microbiome to prevent Parkinson’s in people who are at risk, slow or stop progression in people who have the disease, and use the microbial composition to prescribe the right drug to the right patient to maximize efficacy and avoid side effects.
Study details The new Department of Defense-funded study will address a number of crucial questions. Its aims are to identify the specific microorganisms that contribute to the pathogenesis of Parkinson’s; to identify any micro-organisms that interact with the dozens of known genetic risk factors for the disease; to test the effects of two neuroprotective factors, cigarette smoking and caffeine consumption, on the microbiome; to look for early microbial changes in patients with REM sleep behavior disorder, a sleep disorder that is strongly linked with eventual Parkinson’s diagnoses; and to investigate the interaction between micro-organisms and Parkinson’s progression in animal models of the disease.
Many studies that look at the microbiome in patient populations are too small to produce statistically valid results. That is why the current study will include 1,000 Parkinson’s cases and 600 healthy controls, drawn from UAB and the other members of the NeuroGenetics Research Consortium, including Emory University, Oregon Health and Science University, the University of Washington in Seattle, and Albany Medical Center in New York. The study will also enroll 100 individuals with REM sleep behavior disorder from UAB and Montreal, Canada.
“Eighty percent of people with REM sleep behavior disorder go on to be diagnosed with Parkinson’s or another neurodegenerative disease,” Payami said. “If we can see changes in the microbiomes of these patients decades before they develop Parkinson’s, we could take action. That’s what’s exciting.”
Co-investigators on the project are David Standaert, M.D., Ph.D., professor and chair; and Amy Amara, M.D., Ph.D., assistant professor, UAB Department of Neurology; and Ron Postuma, M.D., a neurologist from McGill University, Montreal, Canada.