The first test in a mammalian model of a potential new class of drugs to treat Parkinson’s disease shows abatement of neurodegeneration in the brains of test rats and no significant toxicities, UAB and Pfizer Inc. researchers report online in The Journal of Biological Chemistry.

At present, there are no therapies to slow the progression of Parkinson’s disease, a common neurodegenerative disorder that affects up to 10 million people worldwide.

The rat model overexpresses the protein -synuclein in one side of the brain. This leads to degeneration of the dopamine-generating neurons of the substantia nigra region of the brain.

“Because our observations were limited to a four-week period, we are not sure whether neurodegeneration associated with -synuclein is truly prevented or just delayed,” senior author Andrew West, PhD wrote. “Either way, any interruption of neurodegeneration associated with Parkinson’s disease might represent a significant therapeutic advance.”

The rat model used mimics two cardinal features of Parkinson’s disease: degeneration of dopamine neurons in the brain, and the accumulation of alpha-synuclein in surviving neurons. Patients with Parkinson’s have significant degeneration of dopaminergic neurons in the substantia nigra, up to 70 percent losses at even mid-stages of their disease, and abnormal accumulation of -synuclein in many of the surviving neurons that occurs years earlier. Details of how Parkinson’s begins and progresses are still unclear.

The potential new class of drugs is kinase inhibitors that are active against the enzyme “leucine-rich repeat kinase 2” (LRRK2, pronounced “lark two”). Two clues point to LRRK2 as a possible target for therapy in Parkinson’s. First, about two percent of Parkinson’s disease patients have a specific mutation in LRRK2 called G2019S that increases the kinase activity of LRRK2; this suggests that increased activity plays a role in progression of the disease. Second, the West lab last year reported that gene “knockout” rats with no LRRK2 are completely protected from neurodegeneration in the -synuclein-overexpression model, suggesting pharmacological inhibition may be a viable approach.

The model uses rats that express a cloned human G2019S-LRRK2 gene. Then these rats are injected in the brain (specifically the substantia nigra) with a virus that expresses human -synuclein. Test rats were fed the test inhibitor for four weeks, beginning at the time of infection. The small-molecule inhibitor easily passes through the blood-brain barrier to reach the brain from the bloodstream. Besides protecting against neurodegeneration, the inhibitor also lessened an inflammatory response by microglial cells seen in the brain in association with G2019S-LRRK2 expression.

West and colleagues also tested the inhibitor in outbred, wild-type rats, animals that are distinct from the strain that has the human G2019S-LRRK2. With the placebo, these rats showed about a 20 percent loss of neurons after four weeks of -synuclein overexpression; but treatment with the inhibitor completely abated that loss. This result suggests that the inhibitor also has efficacy in the absence of the human G2019S-LRRK2.

“That is important because only two percent of Parkinson’s disease patients have the G2019S mutation,” West said. “These wild-type rats really excited us because it suggests the therapeutic action of the drug may extend to the majority of Parkinson’s disease patients.”

The First Toxin Ever Found for M. Tuberculosis

Despite 132 years of study, no toxin had ever been found for the deadly pathogen Mycobacterium tuberculosis, which infects nine million people a year and kills more than one million.

Now Michael Niederweis, PhD, professor of microbiology at the UAB, and colleagues have described the first known toxin of this pathogenic bacterium. This toxin — Tuberculosis Necrotizing Toxin, or TNT — is the founding member of a novel class of previously unrecognized toxins present in 246 bacterial and fungal species, as determined by protein sequence similarity. Before the Niederweis discovery, those toxins were identified only as the “Domain of Unknown Function 4237.”

Bacteria with those newly recognized toxins include Yersinia pestis, the pathogen that caused the bubonic plague known as the Black Death in Medieval Europe, and Listeria monocytogenes, one of the most deadly food-borne infections and the cause of Blue Bell Creameries recalls this year.

The lack of an identified toxin in M. tuberculosis had contrasted with nearly all other pathogenic bacteria whose toxins contribute to illness or death.

M. tuberculosis is notable for its survival inside macrophages, the immune cells that ingest and destroy infectious bacteria. The newly identified TNT plays a key role to induce necrotic death of the infected macrophage. Thus, TNT enables the M. tuberculosis bacteria to escape from the macrophage and disseminate to other host cells in a person infected with tuberculosis, thus contributing to the survival of M. tuberculosis and spreading the disease.

“The battle between M. tuberculosis and the human immune system to control the fate of infected macrophages is critical in determining the outcome of the infection,” Niederweis wrote in the TNT paper. “The control of host cell death is of utmost importance for the survival, escape and dissemination of M. tuberculosis.”

Drug Improves Cognition in Alzheimer’s Disease-Model Mice

Long-term administration of a drug that mimics the hunger-signaling hormone ghrelin protected Alzheimer’s disease-model mice from memory deterioration, despite a high-glycemic-index (GI) diet, according to research published in the journal Scientific Reports by UAB investigator Inga Kadish, PhD and colleagues.

In 2013, Kadish found that long-term (four months) administration of the ghrelin agonist — an experimental drug that binds to the ghrelin receptor and produces a greater response than ghrelin — protected Alzheimer’s disease-model mice from memory deterioration. The current paper expands that research by including a possible risk factor for Alzheimer’s disease, the high-GI diet.

With chronic diseases like diabetes and Alzheimer’s, you need to do a long-term study,” said Kadish, an assistant professor in the Department of Cell, Developmental and Integrative Biology, UAB School of Medicine. “So we did the long-term experiment with the worst-case scenario, a high-GI diet. Alzheimer’s disease has 10 or 20 risk factors, and some of the strongest risk factors are diabetes or metabolic syndrome.”

In contrast to short-term administration of the ghrelin agonist drug — which impairs insulin sensitivity and glucose tolerance, which are signs of metabolic syndrome and diabetes — the researchers found that the long-term ghrelin agonist treatment did not impair insulin signaling and glucose tolerance in Alzheimer’s disease mice fed a high GI diet.

The Alzheimer’s disease-model mice have three mutations in the amyloid beta (A4) precursor protein that have come from human families in Sweden, the Netherlands and Iowa that have familial Alzheimer’s. These mice show a deterioration in spatial learning as they age.

The test mice fed with the ghrelin agonist and the high-GI diet showed long-term cognitive enhancement as compared to the mice fed with a normal diet or high-GI diet only. The test mice were also more active with reduced body weight and fat mass. And the test mice showed a beneficial impact of the long-term ghrelin agonist treatment on insulin signaling pathways in hippocampal brain tissue. Alzheimer’s patients show significant shrinkage of the hippocampus, a part of the brain cortex that has a key role in forming new memories.

The present results suggest that ghrelin might improve cognition in Alzheimer’s disease via a central nervous system mechanism involving insulin signaling.

AQAF Leaders Named to Malcolm Baldrige Award Board

Alabama Quality Assurance Foundation (AQAF) CEO Wes Smith, MD and Vice President of Quality Liz Prosch, have been named to the Board of Examiners for the 2015 Malcolm Baldrige National Quality Award. The Baldrige Award is the nation’s highest honor for organizational innovation and excellence.

Appointed by the National Institute of Standards and Technology Director, examiners are responsible for reviewing and evaluating applications submitted for the Baldrige Award, as well as other assessment-related tasks. The examiner board is composed of more than 350 leading experts selected from industry, professional, trade, education, health care and nonprofitvorganizations from across the United States.

Named after Malcolm Baldrige, the 26th Secretary of Commerce, the Baldrige Award was established by Congress in 1987. Awards may be given annually to organizations in each of six categories: manufacturing, service, small business, education, health care and nonprofit.

Snowmageddon Survivor to Speak at Medical West Meeting

Medical West’s Diabetic Education Meeting in September will feature special guest speaker, Kelly Garner. During the “snowmageddon” storm of 2013, Garner was helping a stranded motorist when he suddenly disappeared.

As the temperature dropped to 9° F that night, the worst was feared for Garner. When a search party found him at the bottom of a 40 foot ravine the next morning, they were astonished to find that he was still alive. With a head injury and multiple broken vertebrae in his back, not to mention being out all night in the frigid temperature, it was doubtful he would survive, and if he managed to live, he was not expected to ever walk again or have meaningful brain function.

In the end, not only did Garner survive, but he completed the Mercedes Half-Marathon this past February.

Garner, a diabetic himself, will share his story of endurance and the importance exercise played in his recovery.

The meeting will be held on Thursday, September 24th at 6 p.m. at Medical West Hospital - Civic Room located on Level C of the Professional Building. Please call or email to register for this meeting at 205.481.7496 or smaxwell@uabmw.org.

Gregory Mayberry, MD Joins Norwood

Gregory F. Mayberry, MD is joining the Department of Family Medicine at Norwood Clinic Brookwood.

Mayberry is board certified in Family Medicine. He received his medical degree from Saba University School of Medicine in the Netherlands and completed his residency at St. Vincent’s East as Chief Resident.

Gardendale Physician Associates Joins St. Vincent’s

Gardendale Physician Associates has joined St. Vincent’s Health System. The new practice name is St. Vincent’s Primary Care – Gardendale.

“Gardendale Physician Associates decided to move our medical practice to Gardendale over ten years ago. With the support of patients in this area we have been very successful,” said Nolan L. Hudson, MD, FACP, Medical Director for Gardendale Physician Associates. “Major changes in healthcare are coming. In order to preserve what we have accomplished and continue to provide services for this area in the future, we felt it was important for us to align with a major health system in the Birmingham area. We look forward to a long and rewarding relationship with St. Vincent’s for us and our patients.”

Sirote’s Pate Honored as Lawyer of the Year in Birmingham Healthcare Law

Sirote & Permutt  healthcare attorneys Lenora Pate and Cynthia Ransburg-Brown were included in The Best Lawyers in America© for 2016. The annual directory recognizes those who most excel in the legal profession based upon evaluations by colleagues and other legal professionals.

In addition to her recognition among the best lawyers in the healthcare category, Lenora Pate was also specifically chosen as 2016 Health Care Law “Lawyer of the Year” for Birmingham. According to Best Lawyers, “Only a single lawyer in each practice area in each community is being honored as a ‘Lawyer of the Year.’”

UAB Adds Leading Surgeon as head of Department of Surgery

Herbert Chen, MD, an internationally recognized surgeon and medical educator, has been named chair of the Department of Surgery at the UAB School of Medicine and surgeon-in-chief of UAB Hospital.

Chen comes to UAB from the University of Wisconsin School of Medicine and Public Health, where he is the Layton F. Rikkers, MD, Chair in Surgical Leadership, chair of the Division of General Surgery, vice chair of Research for the Department of Surgery and professor in the departments of Surgery, Biomedical Engineering and Pediatrics.

Chen will succeed longtime chair Kirby I. Bland, MD, who will continue his surgical practice as he steps down from the top post after 16 years of leadership.

Chen is a specialist in endocrine surgery, specifically in thyroid disease, hyperparathyroidism, adrenal neoplasms and neuroendocrine tumors. He has mentored more than 100 faculty, postdoctoral fellows, residents, medical students and undergraduates in his lab. He has published more than 430 research and review articles and has edited 12 textbooks.

A native of Wisconsin, Chen received his undergraduate degree from Stanford University and began his medical education at the Duke University School of Medicine, graduating in 1992.

Monheit One of Few Worldwide to Treat with KYBELLA™

Total Skin and Beauty Dermatology Center is the first in Alabama to introduce the FDA-approved injectable drug, KYBELLA™ which is used to improve the appearance of submental fullness, often referred to as double chin.

Gary Monheit, MD, Total Skin & Beauty’s founding dermatologist, is one of the few doctors worldwide trained to administer KYBELLA™.

“I have worked on the clinical studies of this product for the last 10 years, and it has been a satisfying journey. Now we have a nonsurgical method to remove submental fat and correct neck and chin contour,” Monheit said.

Each in-office treatment session is typically 15 to 20 minutes. When injected into subcutaneous fat, KYBELLA™ causes the destruction of fat cells. Once destroyed, those cells cannot store fat. After the aesthetic response is achieved with KYBELLA™, re-treatment is not expected.

Many patients experience visible results in two to four treatment sessions spaced at least one month apart. Up to six treatments may be administered.

The most common side effects are swelling, bruising, pain, numbness, redness and formation of areas of hardness in the treatment area. In clinical trials, the incidence and severity of most side effects decreased with subsequent treatments. KYBELLA™ can cause serious side effects, including trouble swallowing and nerve injury in the jaw that can cause an uneven smile or facial muscle weakness.

Tara Fales, MD Joins Cullman Regional

Cullman Regional Medical Center welcomes Tara Mitchell Fales, MD to the Medical Staff. Fales, who is joining Cullman Internal Medicine & Pediatrics, received her medical degree in 2012 from The UAB School of Medicine after completing her undergraduate studies in Healthcare Management from The University of Alabama. Fales completed her Pediatric Residency Program at The University of Tennessee Health Science Center in Memphis, Tennessee in June 2015.

Waller Receives Top Honors from AHLA for 9th Consecutive Year

Waller, one of the nation’s preeminent law firms serving the healthcare industry, recently received Top Honors from the American Health Lawyers Association (AHLA) for the firm’s continued commitment to the advancement of professional development in healthcare law through its participation in the AHLA. The June 2015 issue of AHLA Connections magazine highlights Waller as the nation’s fourth largest healthcare law firm based on AHLA membership with 163 current members. This is the firm’s ninth consecutive year on the industry-esteemed Top Ten list.

Bill Clifford, MD Joins Trinity

William P. “Bill” Clifford, MD has joined the practice of Trinity Medical Clinics at Chelsea. 

Clifford, who is board certified in Family Medicine, received his medical degree from UAB. He completed his residency with the Mayo Clinic and the University of Alabama. Prior to medical school, Clifford received his Juris Doctorate degree from Emory University School of Law.

A member of the Alabama National Guard, Clifford is a flight surgeon and has served in both Afghanistan and Kosovo.