Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation provides $2 million for study of cellular events that precede Alzheimer’s

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SAN ANTONIO (Feb. 4, 2015) — The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation is giving $2 million to further Alzheimer’s disease research at The University of Texas Health Science Center at San Antonio.

Martin Paukert, M.D., assistant professor of physiology in the School of Medicine, is the principal investigator of the five-year grant. Dr. Paukert and his team are studying activities in the brain that may take place long before Alzheimer’s disease symptoms are observed.

One of the earliest sites of noticeable neurodegeneration is a brain stem structure called the locus coeruleus. This structure has a major influence on the entire central nervous system because it delivers norepinephrine, a neurotransmitter associated with attention or arousal. Initial triggers of Alzheimer’s disease may include less norepinephrine release, and fewer norepinephrine-dependent calcium spikes in cells called astrocytes. While astrocytes are the major support cells for neurons, in Alzheimer’s this relationship appears to be somehow affected, causing the death of neurons.

Dr. Paukert’s team is measuring calcium signals from astrocytes in real time while mice walk on tiny treadmills. “The hope is that we can use these signals as a readout of how much pharmaceutical manipulation is necessary to normalize norepinephrine signaling, and to see whether this intervention slows the progression of Alzheimer’s disease,” Dr. Paukert said.

The team will develop mouse models in which genes can be altered to produce Alzheimer’s-like effects. “The mice would be halfway to Alzheimer’s when we stop the genetic manipulations,” Dr. Paukert said. “We want to know whether the brain, including its support cells, possesses the ability to evade further damage.”

An important contribution to the studies will be the expertise of Manzoor Bhat, Ph.D., professor and chairman of the Department of Physiology, in establishing mouse models, and the expertise of Veronica Galvan, Ph.D., assistant professor of physiology and investigator with the Barshop Institute for Longevity and Aging Studies, in relating cellular changes to effects on Alzheimer’s- like memory deficits. Dr. Bhat occupies the Zachry Foundation Distinguished Chair in Neurosciences at the Health Science Center.

Dr. Paukert joined the Health Science Center in December 2013 from the Johns Hopkins University School of Medicine in Baltimore. “He represents a new generation of neuroscientists, who not only use but develop state-of-the-art, cutting-edge technology to address fundamental questions that go to the heart of neurobiological diseases in a living animal,” Dr. Bhat said.

“The Paukert lab is in its early phases in San Antonio, and funding from The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation will have a major impact on how quickly they can get the animal models established to address the central questions related to the early onset and progression of Alzheimer’s disease in real time, and in the future this will allow exploration of new avenues for therapeutic intervention,” Dr. Bhat said.

 

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 31,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

Anti-epilepsy drug preserves brain function after stroke

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SAN ANTONIO (Feb. 4, 2015) — New research suggests that an already-approved drug could dramatically reduce the debilitating impact of strokes, which affect nearly a million Americans every year.

In the study, one dose of the anti-epilepsy drug, retigabine, preserved brain tissue in a mouse model of stroke and prevented the loss of balance control and motor coordination. Researchers from the School of Medicine at The University of Texas Health Science Center at San Antonio conducted the study, which was published Feb. 3 in The Journal of Neuroscience.

Hours after a stroke, both treated mice and a control group of mice were placed on a balance beam to observe motor coordination. The untreated mice displayed a pronounced loss of coordination with slips and falls. Treated mice had no difficulty with balance, ambulation or turning around on the beam.

“You couldn’t even tell they had a stroke,” said senior author Mark S. Shapiro, Ph.D., professor of physiology at the UT Health Science Center San Antonio. “They ran across the balance beam like gymnasts.”

Histological analysis of the brain tissue of treated mice showed significantly reduced damage to the tissue after the stroke, compared to untreated mice. The protective effects of the medication were observed in treated mice up to five days after the stroke, said Sonya Bierbower, Ph.D., postdoctoral fellow and lead author of the report.

Future studies will assess how long brain function can be protected after a stroke, and whether injury-related seizures can be prevented. “We are also going to see if we can prevent strokes in high-risk animal models,” Dr. Bierbower said.

Retigabine and similar agents open specific proteins called potassium ion channels, whose action stops the electrical activity of nerve cells in the brain. The San Antonio team studied ischemic stroke, in which oxygen and nutrients are suddenly cut off due to a clot in a blood vessel. This is the type of stroke most often seen in humans. “We thought if we could stop the neurons from firing, stopping their electrical activity, we could conserve their resources until the time their blood supply was restored,” Dr. Shapiro said. “This proved to be the case.”

Cells starved of oxygen and nutrients for six hours are compromised and the process of dying is nearly impossible to reverse. Moreover, when cells die, they release factors that trigger many types of responses including an inflammatory response, leading to more cell death in the areas around the blood clot.

A drug called tissue plasminogen activator (tPA) treats stroke by dissolving clots to restore blood flow, but this has significant limitations. tPA causes severe thinning of the blood, so it is not an option for patients who have high blood pressure, a history of bleeding or weak blood vessels. tPA is most effective in the first hours after a stroke, but its later use may do more damage than good.

Potassium channel openers such as retigabine work on a completely different system. “They have nothing to do with thinning blood, but preserving cells by putting a brake on their electrical activity,” Dr. Shapiro said.

“It’s treating the first step in the sequence and stopping the more damaging secondary effects,” Dr. Bierbower said. “These agents directly affect the nerve cells themselves.”

Because retigabine is approved by the U.S. Food and Drug Administration under the American brand name Ezogabine as an anticonvulsant, physicians may use it off label in stroke patients. FDA approval for specifically this drug as stroke therapy will require a clinical trial to be conducted, and a team of neurologists and neurosurgeons at the Health Science Center is considering it, Dr. Shapiro said.

“As a leading cause of death and disability, stroke poses a major risk to our society,” said David F. Jimenez, M.D., FACS, professor and chairman of the Department of Neurosurgery at the Health Science Center. “It is very exciting to see that our collaborative work with our colleagues in physiology could provide a superb way to ameliorate the harmful effects of stroke on our patients.”

Drs. Bierbower and Shapiro both received funding from the National Institute of Neurological Disorders and Stroke to conduct this study. A grant from the American Heart Association has been applied for to further this work. James D. Lechleiter, Ph.D., professor of cellular and structural biology in the School of Medicine, is a co-author of the study.

 

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 31,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

Griffith studies link between aging, autoimmune disease

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SAN ANTONIO (Jan. 30, 2015) — Ann V. Griffith, Ph.D., one of the newest members of the faculty at The University of Texas Health Science Center at San Antonio, is delving into why the appearance of autoimmune disease is linked with aging.

Dr. Griffith joined the Department of Microbiology and Immunology in the School of Medicine on Jan. 1 from The Scripps Research Institute-Florida. She received her Ph.D. degree from The University of Texas Health Science Center at Houston in 2006 in the field of immunology/carcinogenesis.

She leads research on the thymus, a primary organ of the immune system in the neck of humans that functions especially in the development of the immune system. The Griffith team recently showed that one of the primary mechanisms for inducing self-tolerance in the thymus deteriorates with age. The lab is studying the possibility that T cells with potentially self-reactive T cell receptors accumulate with age. (A T cell is a type of white blood cell that develops in the thymus. A receptor is a surface protein on a cell that recognizes other proteins.)

Her lab also studies, among many other topics, the mechanisms and consequences of age-induced thymic atrophy and thymic regeneration. The consequences of thymic atrophy include diminished vaccine response and increased susceptibility to infection. The team’s ultimate goal is to develop novel approaches to extend health span during aging.

 

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 31,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

Mays Family Foundation gives $5 million to CTRC

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SAN ANTONIO (January 22, 2015) — Lowry and Peggy Mays have long been involved in helping the Cancer Therapy & Research Center become the premiere cancer treatment and research center in South Texas.

On Jan. 21, at the CTRC’s 40th Anniversary Reunion Dinner, they announced a gift of $5 million from the Mays Family Foundation.

“We are delighted to honor the CTRC for its 40 years of life-changing work and support its aspirations for the future,” Lowry Mays said.

The $5 million will endow the Mays Family Foundation Distinguished University Presidential Chair for the Director of the CTRC, and will accelerate the progress of the CTRC at The University of Texas Health Science Center at San Antonio to a new level of excellence.

“This endowment is an extraordinary gift that will fuel opportunities for scientific breakthroughs and invest in the best and brightest minds in cancer research,” said CTRC director Ian M. Thompson Jr., M.D.

In a time of diminishing funding for scientific research, the Mays Family Foundation chair will allow for investment in important programs such as pilot research, faculty recruitment and retention, clinical trials, new technology and cancer prevention.

“It is a remarkable testament to the Mays’s continuing commitment to the community, and to the important role the CTRC has played herein, that they are not only early supporters and the founders of the CTRC Cabinet, but now have committed to helping us reach ever-higher standards of excellence,” Dr. Thompson said.

“They planted a seed that has grown into a full tree,” he said. “Now they’re planting again, and we’re soon to have an orchard.”

The Mays Family Foundation, formed in 1994, is committed to supporting the community through causes that empower, enrich and educate. Combined with the Clear Channel Foundation, it has contributed over $55 million to the communities in which the family lives, works or serves.

 

The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the elite academic cancer centers in the country to be named a National Cancer Institute (NCI) Designated Cancer Center, and is one of only four in Texas. A leader in developing new drugs to treat cancer, the CTRC Institute for Drug Development (IDD) conducts one of the largest oncology Phase I clinical drug programs in the world, and participates in development of cancer drugs approved by the U.S. Food & Drug Administration. For more information, visit www.ctrc.net.

Lodge gains early career award from U.S. pharmacology society

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SAN ANTONIO (Jan. 22, 2015) — Daniel Lodge, Ph.D., a psychiatric disorders researcher at The University of Texas Health Science Center at San Antonio, will receive an early career investigator award this year from the American Society for Pharmacology and Experimental Therapeutics (ASPET).

Dr. Lodge, who discovered that transplanting stem cells into the rat brain restored functions that are abnormal in schizophrenia, will be honored at the ASPET annual meeting beginning April 28 in Boston. His award is from ASPET’s Neuropharmacology Division.

Dr. Lodge also was invited to become a member-at-large on the ASPET Neuropharmacology Executive Committee in 2016.

Dr. Lodge is an assistant professor of pharmacology in the School of Medicine at the UT Health Science Center and a member of the institution’s Center for Biomedical Neuroscience. He earned his Ph.D. in 2003 at the University of Monash in his native Australia and completed a postdoctoral fellowship in neuroscience at the University of Pittsburgh.

 

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 31,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

Despite recent thinking, UT Health Science Center study shows diabetic patients can benefit from dental implants

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SAN ANTONIO (Jan. 20, 2015) – For some 20 years, dentists have been reluctant to place dental implants on patients with diabetes because of problems they often have with slow healing and high infection rates.

A new study by researchers at The University of Texas Health Science Center at San Antonio shows that, with some accommodations, diabetic patients ― even those with poorly controlled diabetes ― had as high a success rate with implants after one year as patients with no high-blood-sugar issues.

The study, which appears in the December edition of the Journal of the American Dental Association, was led by Thomas Oates, D.M.D., Ph.D. Dr. Oates is interim associate dean for research and assistant dean for clinical research in the School of Dentistry. He also is a professor and vice chair of the Department of Periodontics at the UT Health Science Center.

Periodontics is the study of the underlying bone and gums that provide the structure for teeth. When a tooth is lost, a dental implant, usually made of metal or another material, can be permanently implanted in the jawbone to become the base for a false tooth.

“The most striking thing to me about the study is that we are not only able to see that dental implants can be successful for patients with diabetes, but that the patients are truly benefitting from them,” Dr. Oates said. “We were seeing dramatic results.”

The 110 patients who completed the study were divided into three groups:

• Patients without diabetes, who were defined as having an A1C glycemic blood test score of less than 6 percent.

• A group with controlled diabetes, which had a glycemic blood score between 6 percent and 8 percent.

• And a third group that had poorly controlled diabetes, defined as a score of 8 percent or higher on the A1C blood glycemic blood test.

Each patient had two implants placed in the lower jaw followed later by placement of a full set of dentures anchored to the implants. After the implants were placed, patients were followed for at least one year. Diabetics, like nondiabetic patients, had nearly 100 percent implant success rates.

“The study findings showed no significant differences between the nondiabetic and well-controlled diabetic groups. The group with poorly controlled diabetes required a longer time for the implant to heal before placing the dentures,” Dr. Oates said. For this reason, there was a four-month healing time following implantation for all groups instead of the usual two months. All patients were prescribed antibiotics and a chlorhexidine gluconate mouth rise following implantation to guard against infection.

Two patients had failed implants early in the study, but were able to receive new implants that healed and were successful at one year. Only seven patients did not complete the study of the original 117 who were screened.

The study was supported by two grants from the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health. Additional funding from the NIDCR is supporting an extension of the study that will allow researchers to follow the patients through five or more years to see if the implants continue to be successful.

Dr. Oates said more investigation is needed before drawing major conclusions. For example, he wants to investigate which variables in the study will produce the best result, as well as how patients will deal with the potential for infections over the long term.

For more information about the study, call (210) 567-5076.

 

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 31,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.