UAB Neurology and Neurosurgery ranked as “Best Hospital” for Neurology and Neurosurgery
UAB Hospital remains at top in Birmingham and Alabama, and rises in several specialty rankings in 2016-2017 U.S. News & World Report Best Hospitals report.
The UAB Health System is dedicated to providing every patient with the best experience and highest quality care available.
U.S. News & World Report’s 2016-2017 Best Hospitals report ranks UAB Hospital No. 1 in Birmingham and Alabama, and nine UAB specialties are listed among the nation’s top 50, up from six specialties the previous year.
“We are proud to be one of the best hospitals in America, and located in Alabama,” said Health System CEO Will Ferniany. “UAB Medicine is something all people in Alabama should be proud of. We even have a bumper sticker that says ‘Our Nationally Ranked Team Wears Scrubs.’ While we are nationally ranked and internationally known, our faculty and staff never forget they are here to serve the people of Alabama with the best medical care possible.”
Rheumatology (11), Gynecology (16) and Nephrology (20) appeared in the nation’s top 20; Neurology and Neurosurgery (25), Pulmonology (29), Ear, Nose and Throat (29), and Diabetes and Endocrinology (30) appeared in the top 30; and Cardiology and Heart Surgery (37) and Urology (47) rounded out UAB’s highest-ranked programs.
The biggest jumps in rankings came from Ear, Nose and Throat and Diabetes and Endocrinology, which were ranked as high-performing last year and both leapt to top-30 national rankings this year. Cardiology and Heart Surgery went unranked last year and appeared at 37 this year. Rehabilitation, Orthopedics, Cancer and Geriatrics all earned the high-performing designation.
Rankings like U.S. News & World Report’s are just one tool available to patients as they make informed decisions about their health care, Ferniany says. UAB Medicine recently launched another when it became the first care provider in Alabama to empower patients to publicly rate and review its physicians — a reliable source of verified and up-to-date information from actual patients in UAB’s Find a Provider directory. The rating and reviews feature gives patients an alternative to third-party rating sites that often exist with little if any oversight and feature outdated, inaccurate and in some cases libelous information. At its launch, more than 81 percent of eligible UAB physicians had a posted rating of at least four stars on the five-star scale.
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UAB researchers discover why brain neurons in Parkinson’s disease stop benefiting from levodopa
In research to prevent this side effect and extend the usefulness of L-DOPA — which is the most effective drug treatment for Parkinson’s disease — University of Alabama at Birmingham researchers have uncovered an essential mechanism of this long-term memory for L-DOPA-induced-dyskinesia, or LID.
They report a widespread reorganization of DNA methylation — a process in which the function of DNA is modified — in brain cells caused by L-DOPA. They also found that treatments that increase or decrease DNA methylation can alter dyskinesia symptoms in an animal model.
Thus, modification of DNA methylation may be a novel therapeutic target to prevent or reverse LID behavior.
“L-DOPA is a very valuable treatment for Parkinson’s, but in many patients its use is limited by dyskinesia,” said David Standaert, M.D., Ph.D., the John N. Whitaker Professor and chair of the Department of Neurology at UAB. “Better means of preventing or reversing LID could greatly extend the use of L-DOPA without inducing intolerable side effects. The treatments we have used here, methionine supplementation or RG-108, are not practical for human use; but they point to the opportunity to develop methylation-based epigenetic therapeutics in Parkinson’s disease.”
The research by David Figge, Karen Eskow Jaunarajs, Ph.D., and corresponding author David Standaert, Center for Neurodegeneration and Experimental Therapeutics, UAB Department of Neurology, was recently published in The Journal of Neuroscience.
Research detailsAlthough studies of LID in animal models have shown changes in gene expression and cell signaling, a key unanswered question still remained: Why is the neural sensitization seen in LID persistent when delivery of L-DOPA is transient?
The UAB researchers suspected DNA methylation changes — the attachment of a methyl group onto nucleotides in DNA — because methylation is known to stably alter gene expression in cells as they grow and differentiate. Furthermore, methylation changes in neurons have been shown to be involved during the formation of place memory and the development of addictive behavior after cocaine use.
In general, increased DNA methylation has a silencing effect on nearby gene expression, while removal of the methyl groups enhances gene expression.
Figge and colleagues found that:
- L-DOPA treatment of parkinsonian rodents enhanced the expression of two DNA demethylases.
- Cells in the dorsal striatum in the LID model showed extensive, location-specific changes in DNA methylation, mostly seen as demethylation.
- The changes in DNA methylation were near many genes with established functional importance in LID.
- Modulating global DNA methylation — either by injecting methionine to increase methylation or applying RG-108, an inhibitor of methylation, to the striatum — modified the dyskinetic behavior of LID, down or up, respectively.
Funding for this work came from the Alacare Mary Sue Beard Predoctoral Fellowship, the Jurenko family, the American Parkinson Disease Association, and National Institute of Neurological Disorders and Stroke grant F31NS090641.
Is Alzheimer’s contagious?
July 11, 2016
By Matt Windsor
What if Alzheimer’s disease is caused, at least in part, by infections? An intriguing study in Science Translational Medicine, from researchers at Harvard University, led to provocative speculation in the New York Times and other major news outlets this summer. “I got asked more questions about this paper than probably anything in the last couple of years,” says Erik Roberson, M.D., Ph.D., co-director of the UAB Center for Neurodegeneration and Experimental Therapeutics in the UAB School of Medicine, associate professor of neurology and neurobiology, and Virginia B. Spencer Scholar in Neuroscience at UAB. “It has gotten a lot of people thinking and talking and asking questions.”
First, Roberson says, a little backstory is in order. In 1906, when Dr. Alois Alzheimer reported the first case of the disease that made him famous, he described a mass of “plaques” and “tangles” in the brain of an afflicted patient, known as Auguste D. But it wasn’t until the 1980s, Roberson explains, that researchers discovered that the main component of those plaques was a protein fragment called amyloid beta; the tangles were made up of a protein called tau.
“The idea that amyloid beta is the main cause of Alzheimer’s disease, what’s known as the ‘amyloid hypothesis,’ has been the main driver in the field” ever since, Roberson says. “There’s lots of evidence that it is part of the disease. That led to lots of trials of drugs to reduce amyloid beta production and inhibitors of aggregation of amyloid beta, but none of those have gone particularly well.”
A new narrative for Alzheimer’sThere are many reasons why that may be the case, Roberson says. For instance, the drugs might not have been able to infiltrate the blood-brain barrier. “But there has been a camp that argues that maybe amyloid beta isn’t the problem,” he says. “Maybe it’s a good thing; part of the brain’s attempt to respond to what is really happening in Alzheimer’s disease.”
Erik RobersonThe Science Translational Medicine paper explores a correlate of that idea — demonstrating that amyloid beta has antibacterial effects. “The main message of the paper is that amyloid beta coats yeast and fungi to prevent them from growing,” says Roberson. That finding “feeds a bigger narrative that has been cropping up over the past year,” he adds: “that infections are the cause of Alzheimer’s disease.”
These wouldn’t need to be life-threatening attacks. The theory, Roberson says, is that “maybe even a mild infection, the kind that many of us are exposed to, could do it. In the course of fighting off that infection, the brain makes amyloid beta to seal the microbes off in plaques, and that ends up having toxic effects.”
This is a “completely different potential cause of Alzheimer’s disease that has not been high on the radar,” Roberson says. In March, a group of about 30 researchers published an editorial in the Journal of Alzheimer’s Disease that summarized the available evidence that microbes could be an Alzheimer’s trigger. “There has been a lot of indirect evidence,” Roberson says. “For example, people with Alzheimer’s disease are more likely to have antibodies against the herpes virus. But that’s not the same thing as proving that herpes is the cause.” Still, the March editorial “got discussion going in the field,” says Roberson, “and I think that is why this subsequent Science Translational Medicine paper attracted so much attention.”
“An interesting idea worthy of more study”It is a “good paper,” Roberson says. “No one paper generally nails down a question in science; it needs to be reproduced and tried in different species, with different types of amyloid beta and other infectious agents, but this is a good start.” And it helps point to the broader question of the ultimate cause of Alzheimer’s disease, Roberson adds.
About 1 percent of people have a genetic mutation that leads to Alzheimer’s, and there are genes that are risk factors in others, “but we don’t really know what is the cause,” Roberson says. The contention that amyloid beta is actually an “antimicrobial peptide is an interesting idea worthy of more study,” but it will be difficult to replicate the research in humans, Roberson points out. “It’s fairly easy to look at this question in animal models, but not in humans. We can only study someone’s brain after they have died, at a much later stage of the disease.”
Investigating a promising therapyMeanwhile, Roberson’s lab is pursuing another longstanding Alzheimer’s question: What is the relationship between amyloid and tau, the protein responsible for the tangles in Alzheimer’s disease? “If you make a mouse without tau, amyloid beta doesn’t have its toxic effects,” Roberson says. “They require the presence of tau to have a full effect. In people, there are questions about that interaction as well. The amyloid beta accumulates in a different part of the brain than the tau accumulates. So maybe you need both of those hits, or maybe one is causing or enabling the other. We still don’t know.”
While they study that very question, Roberson’s team is also moving forward with tests of a compound that blocks the interaction between tau and another protein, fyn, that is important in these processes of Alzheimer’s. “If you get rid of one or the other, it’s a good thing,” Roberson says. “That is easy in mice, but difficult in patients.” Working with drug chemistry experts at Southern Research, Roberson’s lab has found several compounds that could block the tau-fyn linkup. They are now sifting these “hits” to find the most appropriate candidate compounds, Roberson says. “If we can prevent them from interacting, we believe it will have a beneficial effect.”
Discovery may lead to a treatment to slow Parkinson’s disease
Laura A. Volpicelli-DaleyUsing a robust model for Parkinson’s disease, University of Alabama at Birmingham researchers and colleagues have discovered an interaction in neurons that contributes to Parkinson’s disease, and they have shown that drugs now under development may block the process.
The research team has shown that the most common genetic cause of Parkinson’s disease — a mutant LRRK2 kinase enzyme — contributes to the formation of inclusions in neurons, resembling one of the hallmark pathologies seen in Parkinson’s disease. These inclusions are made up of aggregated alpha synuclein protein, which — the research also shows — can be prevented from forming by using two LRRK2 kinase inhibitor drugs now being developed for clinical use.
The interaction between mutant LRRK2 kinase and alpha-synuclein “may uncover new mechanisms and targets for neuroprotection,” the researchers write in a recent Journal of Neuroscience paper. “These results demonstrate that alpha-synuclein inclusion formation in neurons can be blocked and that novel therapeutic compounds targeting this process by inhibiting LRRK2 kinase activity may slow progression of Parkinson’s disease-associated pathology.”
The potential clinical applications for novel neuroprotection strategies in LRRK2-linked Parkinson’s need to be tested in other preclinical models of Parkinson’s disease, say the researchers, led by corresponding author Laura A. Volpicelli-Daley, Ph.D., and senior author Andrew B. West, Ph.D., Center for Neurodegeneration and Experimental Therapeutics, UAB Department of Neurology.
“These data give us hope for the clinical potential of LRRK2 kinase inhibitors as effective therapies for Parkinson’s disease,” Volpicelli-Daley said. “The LRRK2 kinase inhibitors may inhibit the spread of pathologic alpha-synuclein, not only in patients with LRRK2 mutations, but in all Parkinson’s disease patients. Future studies to validate the safety and efficacy of the LRRK2 inhibitors will be necessary before testing the inhibitors in human clinical trials.”
Besides Parkinson’s disease, alpha-synuclein also plays a central role in development of dementia with Lewy bodies and multiple system atrophy, and it is associated with Alzheimer’s disease and other neurodegenerative disorders.
Primary hippocampal neurons from mice expressing G2019S-LRRK2. The neurons were treated with alpha-synuclein fibrils, and 18 days later immunofluorescence was performed. The magenta shows phospho-alpha-synuclein inclusions in the cell bodies and throughout the axons, which are visualized as green.Research detailsThe Parkinson’s disease model developed by Volpicelli-Daley applies very low concentrations of pre-formed fibrils of alpha-synuclein to in vitro or in vivo neurons. This causes formation of modified alpha-synuclein inclusions that share morphology with those found in the Parkinson’s disease brain after death.
They used this model to test the effects of neuron expression of the mutant LRRK2 (“lark two”) kinase, G2019S-LRRK2, on the formation of the inclusion pathology.
They found that:
- G2019S-LRRK2 enhanced alpha-synuclein inclusions in primary hippocampal neurons from the hippocampus region of the brain, 18 days after fibril exposure, as compared with neurons that over-expressed normal LRRK2.
- The effects of G2019S-LRRK2 expression in the fibril-exposed neurons were lessened by very low concentrations of potent and selective preclinical drugs that inhibit LRRK2 kinase. This suggested that the kinase activity of G2019S-LRRK2, which adds a phosphate onto target proteins, underlies the faster formation of pathologic alpha-synuclein inclusions.
- G2019S-LRRK2 expression enhanced alpha-synuclein inclusion formation in dopamine neurons from the region of the brain called the substantia nigra pars compacta. The substantia nigra pars compacta is the area of the brain that dies in Parkinson’s disease, so this experiment further supports a link between the G2019S-LRRK2 mutation and Parkinson’s pathogenesis.
Andrew B. WestIn fluorescence-recovery-after-photobleaching experiments, they found there was a larger pool of mobile alpha-synuclein, as opposed to membrane-bound alpha-synuclein, in neurons that expressed G2019S-LRRK2. Recent work by others has shown that mobile alpha-synuclein is prone to misfolding and aggregation, so the researchers hypothesize that the G2019S-LRRK2 mutation may contribute to Parkinson’s susceptibility by boosting the amounts of mobile alpha-synuclein in neurons.
Besides Volpicelli-Daley and West, co-authors of the paper “G2019S-LRRK2 expression augments alpha-synuclein sequestration into inclusions in neurons” are Hisham Abdelmotilib, Zhiyong Liu, Lindsay Stoyka, João Paulo Lima Daher and Kyle Fraser, all of the Center for Neurodegeneration and Experimental Therapeutics, UAB Department of Neurology; Austen J. Milnerwood, Centre for Applied Neurogenetics, University of British Columbia; Vivek K. Unni, Jungers Center for Neurosciences Research and Parkinson Center of Oregon, Oregon Health & Science University; Warren D. Hirst, Pfizer Neuroscience and Pain Research Unit, Cambridge, Massachusetts; Zhenyu Yue, Departments of Neurology and Neuroscience, Icahn School of Medicine at Mount Sinai; Hien T. Zhao, Ionis Pharmaceuticals, Carlsbad, California; and Richard E. Kennedy, Comprehensive Center for Healthy Aging and Division of Gerontology, Geriatrics, and Palliative Care, UAB Department of Medicine.
Grants to fund this work came from the American Parkinson’s Disease Association, the Michael J. Fox Foundation LEAPS Award and the National Institutes of Health NS064934.
Volpicelli-Daley is an assistant professor in the Department of Neurology.
West is co-director of the Center for Neurodegeneration and Experimental Therapeutics, and the John A. and Ruth R. Jurenko Professor of Neurology at UAB.