Stopping Alzheimer’s disease: Local research study featured in Newsweek
David Geldmacher, M.D., lead investigator, A4 Alzheimer's study at UABNearly 5.4 million Americans suffer from Alzheimer’s disease. According to the 2016 Facts and Figures State Sheet from the Alzheimer’s Association, this includes 89,000 people in Alabama, and experts expect that number to triple by 2050.
With the growing need to address this devastating disease, researchers are shifting their focus from treatment to prevention. This new paradigm could bring hope to millions who may be at risk for developing Alzheimer’s.
A groundbreaking study being conducted at the University of Alabama at Birmingham is looking for volunteers who have the earliest changes in their brain associated with the disease, but do not yet have any symptoms. Healthy people ages 65-85 with normal memory are needed to be screened for this clinical trial, which aims to prevent memory loss associated with the disease.
According to a recent article in Newsweek, experts believe that, by targeting pre-symptomatic participants, they can prevent Alzheimer’s prior to the disease’s developing and causing irreversible damage.
“With this new approach, even partial success — an appreciable slowing of brain degeneration — could have a big impact,” said Reisa Sperling, M.D., a neurologist who directs the Center for Alzheimer’s Research and Treatment at Boston’s Brigham and Women’s Hospital. “Ultimately, we need to start treating people before there are symptoms.”
The study, known as the A4 Study (which stands for the Anti-Amyloid in Asymptomatic Alzheimer’s study) seeks to delay Alzheimer’s-related brain damage and curb memory loss before any outward signs develop.
|“Our focus now is on recognizing Alzheimer’s disease early enough that we can take steps to slow its progression. With advanced imaging equipment and research techniques now available, we can spot Alzheimer’s before symptoms emerge and take appropriate actions.”|
This landmark study takes a new approach to Alzheimer’s research by testing for an elevated level of a protein known as ‘amyloid’ in the brain. Scientists believe that elevated amyloid may play an important role in the eventual development of memory loss and Alzheimer’s.
Researchers say the goal of the A4 Study is to test whether an investigational drug that targets amyloid plaques can help to slow the progression of memory loss associated with Alzheimer’s.
Another major emphasis of the study is to help determine why certain populations, including African-Americans and Hispanics, are more likely than others to develop the disease. The A4 Study is seeking 1,000 healthy participants who may be at risk for Alzheimer’s-related memory loss have no outward signs of the disease. The participants will enroll in study sites across the United States. Researchers estimate that 10,000 people will need to be screened to find 1,000 individuals who qualify for the study.
Potential study volunteers can learn more, including how to enroll, by visiting the A4 Study website at A4study.org.
UAB study shows link between microbiome in the gut and Parkinson’s
Written by Bob Shepard
There is growing evidence showing a connection between Parkinson’s disease — a neurodegenerative condition — and the composition of the microbiome of the gut. A new study from researchers at the University of Alabama at Birmingham shows that Parkinson’s disease, and medications to treat Parkinson’s, have distinct effects on the composition of the trillions of bacteria that make up the gut microbiome.
The findings were published in February in Movement Disorders, the journal of the International Parkinson and Movement Disorder Society.
Haydeh Payami, Ph.D., professor of Neurology“Our study showed major disruption of the normal microbiome — the organisms in the gut — in individuals with Parkinson’s,” said Haydeh Payami, Ph.D., professor in the Department of Neurology, in the UAB School of Medicine.
Payami says, at this point, researchers do not know which comes first. Does having Parkinson’s cause changes in an individual’s gut microbiome, or are changes in the microbiome a predictor or early warning sign of Parkinson’s? What is known is that the first signs of Parkinson’s often arise as gastrointestinal symptoms such as inflammation or constipation.
“The human gut hosts tens of trillions of microorganisms, including more than 1,000 species of bacteria,” she said. “The collective genomes of the microorganisms in the gut is more than 100 times larger than the number of genes in the human genome. We know that a well-balanced gut microbiota is critical for maintaining general health, and alterations in the composition of gut microbiota have been linked to a range of disorders.”
Payami’s team studied 197 patients with Parkinson’s and 130 controls. Subjects came from Seattle, New York and Atlanta.
The study indicated that Parkinson’s is accompanied by imbalance in the gut microbiome. Some species of bacteria were present in larger numbers than in healthy individuals; other species were diminished. Different medications used to treat Parkinson’s also appear to affect the composition of the microbiome in different ways.
“It could be that, in some people, a drug alters the microbiome so that it causes additional health problems in the form of side effects,” Payami said. “Another consideration is that the natural variability in the microbiome could be a reason some people benefit from a given drug and others are unresponsive. The growing field of pharmacogenomics — tailoring drugs based on an individual’s genetic makeup — may need to take the microbiome into consideration.”
The study subjects came from three regions, the Northeast, Northwest and South. Payami says the research team detected an unexpected difference in gut imbalance as a function of geographic site, which may reflect the environmental, lifestyle and diet differences between the three regions.
Another function of the microbiome is to help the body rid itself of xenobiotics — chemicals not naturally found in the body often arising from environmental pollutants. The study found evidence that the composition of bacteria responsible for removing those chemicals was different in individuals with Parkinson’s. This may be relevant because exposure to pesticides and herbicides in agricultural settings is known to increase the risk of developing Parkinson’s.
Payami says the study of the microbiome is a relatively new field, and a better understanding of macrobiotics may provide unexpected answers for Parkinson’s disease and potentially other disorders.
“This opens up new horizons, a totally new frontier,” she said. “There are implications here for both research and treatment of Parkinson’s disease. Therapies that regulate the imbalance in the microbiome may prove to be helpful in treating or preventing the disease before it affects neurologic function.” However, Payami cautions against grand conclusions until more data are available.
Payami says another study is underway at UAB with individuals with Parkinson’s and healthy individuals in Alabama in an effort to replicate and confirm the results.
“The present findings lend support to the notion that the composition of the gut microbiome may hold new information for assessing efficacy and toxicity of Parkinson’s medications,” Payami said. “Additional studies are needed to assess the effects of those drugs, with larger numbers of treated and untreated patients as well as individuals who do not have Parkinson’s.”
The study was supported by funding from the National Institute of Neurological Disorders and Stroke, one of the National Institutes of Health.
NEJM lauds UAB study as one of the top neurology stories of 2016
Gary Cutter, Ph.D., professor of biostatistics, UAB School of Public Health
A study on the efficacy of surgery to remove the thymus in myasthenia gravis patients, led by researchers at the University of Alabama at Birmingham, has been named one of the top neurology stories of 2016 by the New England Journal of Medicine Journal Watch. The results of the MGTX trial were reported in NEJM in August 2016.
The study was the first randomized trial to assess whether surgery to remove the thymus, long a mainstay of treatment for MG, actually provided any benefit or improved clinical outcomes.
Gary Cutter, Ph.D., professor in the Department of Biostatistics in the UAB School of Public Health and principal investigator of the MGTX study, led the multisite, multinational and multidisciplinary study. Inmaculada Aban, Ph.D., professor in the Department of Biostatistics, served as the study’s deputy director and ran the data-coordinating center.
The study enrolled 126 patients with MG without a thymoma, or tumor. Some underwent a surgical procedure to remove the thymus, known as a thymectomy, and received a commonly used MG medication called prednisone. A second group received prednisone alone.
The surgery group had a better Quantitative Myasthenia Gravis score (6.15 vs 8.99) and a lower average requirement for alternate-day prednisone, requiring 44 mg against 60 mg for the medication-only group over the three years of follow-up.
Cutter and colleagues concluded patients treated with thymectomy were less affected by symptoms than those treated with prednisone alone, required less prednisone and other immune-suppressing medications, and had fewer hospitalizations due to flare-ups. The authors wrote that thymectomy improved clinical outcomes over a three-year period in these patients.
Inclusion in the NEJM Journal Watch list is determined through consideration of the relevance to the clinician, coverage of the various fields within neurology, recognition of landmark studies, and media publicity and public awareness.
The MGTX trial was funded by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health.
By Bob Shephard
UAB Media Relations
Four new NSF grants — three in neuroscience — deepen UAB’s research portfolio, forge collaborations
One research team supported by an NSF grant is in the College of Arts and Sciences’ Department of Chemistry, led by a polymer chemist who applies nanotechnology to biological and biomedical challenges. The three other grants will support basic neuroscience studies, one of UAB’s hallmark research strengths.
Lori McMahon, Ph.D., the Jarman F. Lowder Professor of Neuroscience, dean of the UAB Graduate School and director of the UAB Comprehensive Neuroscience Center, highlighted the three neuroscience EPSCoR grants at this fall’s Comprehensive Neuroscience Center retreat, calling them prestigious and competitive.
“UAB neuroscience has never had one NSF grant, and now we have three,” she said. “With the results of these grants, we can increase our funding beyond the National Institutes of Health.”
These four UAB grants, and one additional Alabama-related EPSCoR that supports research teams at the University of Alabama, Tuscaloosa, and the University of Mississippi, set a record, says Christopher Lawson, Ph.D., executive director of the Alabama EPSCoR program and a professor in the UAB Department of Physics.
“The state of Alabama now has more of the EPSCoR Track II grants than any other state; no state has ever had five.”
Only 25 states, two territories and one commonwealth — areas that receive much less NSF funding than the major research universities in the other 25 states — qualify to compete for the Experimental Program to Stimulate Competitive Research grants, known as EPSCoR. The EPSCoR Track II grants are meant to level the playing fields among have and have-not research states, and applicants must form collaborations with researchers from other EPSCoR states. This means the UAB teams have formed synergistic partnerships and collaborations across the Birmingham campus and with scientists in other states to foster regional research strength.
UAB neuroscience teams and their goalsThe three neuroscience EPSCoR grants support a study to understand the initiation of epileptic brain seizures; a project to develop a new tool for optogenetics, which is the control of neural cells using light; and an effort to discover a universal rule for the relation between neural activity and increased blood flow in areas of the brain. In all three EPSCoR grants, UAB is a partner institution, and the lead institution is in another EPSCoR state.
“Several institutions reached out to UAB because we are so strong in neuroscience,” McMahon said. “There is a lot of UAB synergy around the three neuroscience EPSCoRs.”
McMahon says all three UAB neuroscience teams will meet regularly to share results and ideas.
Epileptic brain seizuresFrom left: Roy Martin, Jerzy P. Szaflarski and Timothy Gawne.The current approach for epilepsy surgery at UAB involves two surgeries. The first implants electrodes into a patient’s brain for a two-week period to map the location of the seizure onset zone in the brain. The second operation cuts out the onset zone.
“Our goal is to one day not need invasive monitoring,” said Sandipan Pati, M.D., assistant professor of neurology. “That would mean one surgery instead of two, and the patient would not have to stay in the hospital for two weeks.”
The UAB team in the epileptic brain seizure study — headed by Jerzy P. Szaflarski, M.D., Ph.D., professor of neurology — is developing and validating software for noninvasive brain mapping that will allow caregivers to locate that part of the brain that initiates seizures and locate those parts that function in memory.
“We will provide a road map for the surgeons — where to operate to remove the thumb-sized part of the brain that kicks off seizures, and what parts of the brain to avoid,” Pati said, “so that patients will have no added memory deficits after the operation.”
The investigators will use magnetoencephalography, or MEG, to map electrical activity using the magnetic fields produced by natural electrical currents produced by the brain. The magnetic forces are measured from the outside of the brain as the top of a patient’s head fits into the MEG device, which looks something like a beauty-shop hair drier on steroids. Pati says the UAB team has preliminary data about using the MEG to identify the onset zone by its hyper-excitation, without the need to wait for seizures.
Other UAB investigators in the study are Roy Martin, Ph.D., associate professor of neurology, and Timothy Gawne, Ph.D., associate professor of vision sciences. The lead institution for the study is Louisiana Tech University, and the University of Arkansas is also a partner in the study.
New tool for optogeneticsFrom left: Mark Bolding, Lynn Dobrunz, Lori McMahon and Gary Gray.Optogenetics uses light to control cells in living tissue, after light-sensitive ion channels are introduced into the cells by gene manipulation. Then light is sent into the brain on a fiber-optic cable inserted into the brain, to make neurons fire or to stop neurons from firing. This control helps researchers learn how the brain is wired and how it works.
The optogenetics project will create technology to control the light-sensitive ion channels using low-power X-rays, thus allowing control of neurons from outside the body.
McMahon is the UAB co-principal investigator in this project, which is led by Clemson University. Other partner institutions are the University of New Mexico and the University of South Carolina. The Clemson researchers will develop special nanoparticles that emit light in response to X-rays, the New Mexico researchers will genetically modify the light-sensitive ion channels so that they can bind the nanoparticles, and the UAB researchers will test how those nanoparticles disperse in the brain and how these particles, when activated by X-rays, can turn on and off brain circuits.
“We are about to do the first validation,” McMahon said. “The entire four years of the grant is developing the tool. Then we can use it in animal disease models for Alzheimer’s disease, Parkinson’s disease and anxiety. The goal is to understand brain circuitry using preclinical models of neurologic disease and models of neuropsychiatric illness.”
Other UAB investigators are Lynn Dobrunz, Ph.D., associate professor of neurobiology; Mark Bolding, Ph.D., assistant professor in the Division of Advanced Medical Imaging Research, Department of Radiology, and director of the Civitan International Neuroimaging Facility; Kazutoshi Nakazawa, M.D., Ph.D., associate professor of psychiatry and behavioral neurobiology; and Gary Gray, Ph.D., professor of chemistry.
Neural activity and blood flowJacques Wadiche, Farah Lubin and Paul Gamlin.It has long been known that neural activity is associated with increased blood flow, as the neurons need more oxygen and nutrients. In imaging with functional magnetic resonance, or fMRI, increased blood flow can be seen in parts of the brain as the subjects perform a task. But the resolution — both spatially and in time — is not sharp, and fMRI remains an indirect measure of neural activity.
The UAB team will use a very expensive infrared laser and microscope to peer beneath the surface of living brains to look at individual neurons and capillary beds.
“We will image cells in the brain using two-photon imaging,” said Paul Gamlin, Ph.D., professor of ophthalmology and UAB’s co-principal investigator in the neural activity and blood flow effort. “While monitoring neural activity, we will also monitor what the capillary bed is doing.”
“The question is, if we stimulate the cells, how precise is the blood flow change?”
Capillaries are the smallest blood vessels, bringing oxygen and nutrients to cells and taking away carbon dioxide and waste products. Networks of capillaries form tiny beds of vessels, and each capillary has a precapillary sphincter, a ring of muscle that can control blood flow, akin to crimping a garden hose to lessen water flow. It has been estimated that the human brain has 400 miles of capillaries, and that nearly every neuron in the brain has its own capillary.
Gamlin and others on the UAB team — Lawrence Sincich, Ph.D., assistant professor of vision sciences; Farah Lubin, Ph.D., associate professor of neurobiology; Jacques Wadiche, Ph.D., associate professor of neurobiology; and Yuhua Zhang, Ph.D., assistant professor of ophthalmology — can stimulate neurons nonphysiologically and see how the capillaries change. They will also look at physiological stimulation by shining light on one, two or three retinal cells in the eye and watching how neurons and capillaries in the visual cortex of the brain respond.
The lead institution in this project is the Medical University of South Carolina, and Furman University and the University of South Carolina, Beaufort, are partners in the study.
Detecting pollutants in Gulf Coast marine ecosystemsEugenia KharlampievaThe Gulf Coast aquatic ecosystem hosts important fishing grounds and aquaculture, which co-exist with trading ports, off-shore oil wells and production industries. The fourth UAB EPSCoR is aimed at monitoring the water quality of this ecosystem, under the lead of the University of Southern Mississippi.
Ten researchers at six institutions in Alabama and Mississippi will develop advanced polymer-based, selective sensing technologies to detect and analyze pollutants.
The UAB investigator is Eugenia Kharlampieva, Ph.D., associate professor of polymer chemistry. She will design and synthesize three-dimensional porous hydrogel microparticles. These particles will be filled with sensing molecules created by Marco Bonizzoni, assistant professor of chemistry at the University of Alabama, Tuscaloosa. These hydrogels will eventually become devices that can sense polycyclic aromatic hydrocarbons in sea water.
“Sea water is a challenge because it is very rich in ions from all that salt,” Kharlampieva said. “It is hard to find the right technology that will work in that environment.”
Other researchers in the grant are developing sensitive and selective sensors to measure levels of carbon dioxide, nitrates and phosphates. The goal is new classes of seawater quality sensors that are faster, simpler and less costly. Other partner institutions in the grant are the University of Mississippi, Mississippi State University and Jackson State University.
By Jeff Jeff Hansen
UAB Media Relations