- Evidence that new biomimetic controlled-release capsules may help in gum disease
- Brain enzyme is double whammy for Alzheimer’s disease
- Scientists report promising new direction for cognitive rehabilitation in the elderly
- Brain-wave-reading robot might help stroke patients
Posted: 19 Aug 2012 09:00 PM PDT
Scientists are trying to open a new front in the battle against gum disease, the leading cause of tooth loss in adults and sometimes termed the most serious oral health problem of the 21st century. They described another treatment approach for the condition in a report here today at the 244th National Meeting & Exposition of the American Chemical Society, the world’s largest scientific society.
“Our technology uses controlled-release capsules filled with a protein that would be injected in the pockets between the gums and the teeth,” said Steven Little, Ph.D., who reported on the research. “That’s ground-zero for periodontal disease ? ‘gum disease’ ? the place where bacteria breed and inflammation occurs. The capsules dissolve over time, releasing a protein that acts as a homing beacon. It guides immune cells to the diseased area, reducing inflammation, creating an environment that fights the disease process and even could create conditions favorable for gum tissue to regrow.”
Little and colleagues, who are with the University of Pittsburgh, have evidence from laboratory experiments with mice ? stand-ins for humans in early research of this kind that cannot be done with actual patients ? that the approach does foster healing and regrowth of gum tissue damaged by periodontal disease.
A bacterial infection causes periodontal disease. It first appears as mild tenderness and bleeding of the gums. It leads to inflammation and, if left untreated, can damage the gums so that they recede and lose their attachment to the teeth. It may progress even further and damage bone and other tissues that hold teeth firmly in place. Surprisingly, gum disease has a number of deleterious effects outside the mouth, with some studies linking inflammation in the gums to an increased risk of heart disease, stroke and preterm delivery in pregnant women.
Treatment includes scaling, root planing and other procedures to remove the plaque and bacteria that have accumulated in pockets between the teeth and gums. Dentists may combine this with antibiotics to fight the bacteria involved in gum disease.
Many scientists are seeking alternative treatments that kill the bacteria. Little’s group is taking an entirely different approach. They are targeting the inflammation process. “Although bacteria start the disease, inflammation is what keeps it going and causes progressive damage,” Little explained.
To reduce inflammation at the gums, Little and colleagues designed injectable controlled-release capsules containing a protein encased inside a plastic-like polymer material. The polymer is already used in medicine in dissolvable sutures. After the capsules are injected, the polymer slowly breaks down, releasing the protein encapsulated inside. The protein, termed a chemokine, is already produced by the body’s existing cells in order to summon specialized white blood cells to a specific site. Scientists previously tried to keep those cells, termed lymphocytes, away from the gums so as to block inflammation from occurring in the first place.
“It seems counterintuitive to lure in a lymphocyte, which is traditionally thought of as an inflammatory cell, if there’s inflammation,” Little pointed out. “But remember that a certain level of natural inflammation is required to fight off an infection. Inflammation is inherently a good thing, but too much of it is a bad thing. That’s why we aim to restore the immune balance, or homeostasis.”
Little’s team injected the capsules into mice and discovered evidence that disease symptoms are dramatically reduced and that proteins and other substances involved in regrowth of gum tissue had appeared. Little said that this finding offers encouragement that the treatment could not only rebalance the immune system, but also prompt regrowth of lost gum and bone tissue in the mouth.
The researchers acknowledged funding from the Arnold and Mabel Beckman Foundation, the Wallace H. Coulter Foundation and the National Institute of Dental and Craniofacial Regeneration of the NIH (1R01DE021058-01).
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Periodontal disease is characterized by destructive inflammation of the gums and supporting ligament and is considered the most pressing oral health concern today. Current therapies focus on elimination of the invasive bacteria through clinical procedures known as scaling and root planing and also the use of local antibiotics. However, recent literature suggests that although the bacteria initiate periodontal disease, symptoms are perpetuated by an imbalanced immune response and can even be characterized by an absence of a subset of lymphocytes that can promote immunological hypo-responsiveness and tolerance. We hypothesized that recruiting this subset of lymphocytes back into the periodontium would decrease the symptoms of periodontal disease, and restore immunological homeostasis. In this talk, we will discuss how such targeted, lymphocyte-recruiting formulations appear to indeed abrogate periodontal disease symptoms in both murine and pre-clinical canine models and may even establish a pro-regenerative milieu.
Contact: Michael Bernstein
Posted: 19 Aug 2012 09:00 PM PDT
The underlying causes of Alzheimer’s disease are not fully understood, but a good deal of evidence points to the accumulation of ?-amyloid, a protein that’s toxic to nerve cells. ?-amyloid is formed by the activity of several enzymes, including one called BACE1. Most Alzheimer’s disease patients have elevated levels of BACE1, which in turn leads to more brain-damaging ?-amyloid protein. In a paper published August 15 in The Journal of Neuroscience, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) found that BACE1 does more than just help produce ?-amyloid?it also regulates another cellular process that contributes to memory loss. This means that just inhibiting BACE1′s enzymatic activity as a means to prevent or treat Alzheimer’s disease isn’t enough?researchers will have to prevent cells from making it at all.
“Memory loss is a big problem?not just in Alzheimer’s disease, but also in the normal aging population,” said Huaxi Xu, Ph.D., professor in Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and senior author of the study. “In this study, we wanted to better understand how BACE1 plays a role in memory loss, apart from ?-amyloid production.”
To do this, Xu and his team used a mouse model that produces human BACE1. Mice produce a different type of ?-amyloid, one that’s far less toxic than the human version. So, in this system, they could look solely at how BACE1 functions independent from ?-amyloid formation. If BACE1 only acted to produce ?-amyloid, the researchers would expect to see no effect when mice produce human BACE1?since mouse ?-amyloid isn’t very toxic, extra BACE1 would be no big deal. Instead, they saw that the enzyme still impaired learning and memory, indicating a secondary function at work.
If it’s not producing ?-amyloid, what is BACE1 doing? Many years ago, scientists found that a protein in the brain?protein kinase A (PKA), better known for directing cellular metabolism?also plays an important role in memory formation. In this study, Xu and colleagues found that BACE1 disrupts the cell’s production of other molecules required for PKA function. By that mechanism, BACE1 inactivates PKA and therefore inhibits memory formation in mice, even in the absence of neurotoxic ?-amyloid.
“So BACE1 is a double whammy when it comes to memory,” Xu said. “But that also means that a therapy that targets BACE1 could be a double punch against Alzheimer’s disease, and even just normal aging-related memory loss. That’s why we’re now looking for ways to block BACE1 expression in the brain.”
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Please contact Heather Buschman at email@example.com to schedule on-site, phone, or Skype interviews with Huaxi Xu, Ph.D. Images are also available upon request.
This research was funded by the U. S. National Institutes of Health (National Institute on Aging grants R01AG021173, R01AG030197, R01AG038710, R03AG034366, R01AG018840, R01AG022074, R21AG038968; National Institute of Neurological Disorders and Stroke grants R01NS046673, R01NS057096), the Alzheimer’s Association, the American Health Assistance Foundation, the National Natural Science Foundation of China, the 973 Prophase Project, and the Natural Science Foundation of Fujian Province of China.
In addition to Xu, the study was co-authored by Yaomin Chen, Xiamen University and Sanford-Burnham; Xiumei Huang, Xiamen University and Sanford-Burnham; Yun-wu Zhang, Xiamen University; Edward Rockenstein, UC San Diego; Guojun Bu, Xiamen University; Todd E. Golde, University of Florida; and Eliezer Masliah, UC San Diego.
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. The Institute consistently ranks among the top five organizations worldwide for its scientific impact in the fields of biology and biochemistry (defined by citations per publication) and currently ranks third in the nation in NIH funding among all laboratory-based research institutes. Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a U.S.-based, non-profit public benefit corporation, with operations in San Diego (La Jolla), California and Orlando (Lake Nona), Florida. For more information, news, and events, please visit us at sanfordburnham.org
Posted: 19 Aug 2012 09:00 PM PDT
Research has found that declines in temporal information processing (TIP), the rate at which auditory information is processed, underlies the progressive loss of function across multiple cognitive systems in the elderly, including new learning, memory, perception, attention, thinking, motor control, problem solving, and concept formation. In a new study, scientists have found that elderly subjects who underwent temporal training improved not only the rate at which they processed auditory information, but also in other cognitive areas. The study is published in the current issue of Restorative Neurology and Neuroscience.
“Our study showed for the first time significant benefits of temporal training on broad aspects of cognitive function in the elderly. The results were long-lasting, with effects confirmed 18 months after the training,” says lead investigator Elzbieta Szelag, Professor, Head of Laboratory of Neuropsychology, Nencki Institute of Experimental Biology (www.nencki.gov.pl), and Warsaw School of Social Sciences and Humanities (www.swps.pl), Warsaw, Poland.
Thirty subjects between 65 and 75 years of age were randomly assigned to three groups. One group received temporal training using Fast ForWord Language® (FFW), a program comprised of several computer games designed to improve memory, attention, and sequencing abilities. The program was developed to help children who have trouble reading, writing, and learning. The second group participated in non-temporal training by playing common computer games. The third group, the control, underwent no training.
Prior to the training, all of the subjects went through a number of tests to measure their cognitive functioning. Two tasks assessed TIP by measuring sequencing abilities. Specifically, at which inter-stimulus-interval subjects could identify the order of two stimuli presented in rapid sequence, i.e. which of two tones was higher or lower, or whether they heard a sound in the right or left ear first. Three aspects of attention were assessed: the ability to sustain attention over a longer period of time (vigilance), the ability to pay attention to multiple processes (divided attention), and the ability to maintain a high level of attention in anticipation of a test stimulus (alertness). Short-term memory was assessed with tests to evaluate working memory span, the ability to match complex patterns, and the ability to recognize a pattern seen earlier.
Each subject in the temporal training group started with exercises from the basic module of FFW. When they reached 100% complete for each exercise, they moved onto an intermediate program, and then an advanced program. They trained for an hour a day, four days a week, for eight weeks. The non-temporal training group played computer games such as Solitaire or Internet games such as Mahjong for the same amount of time. The control group received no training but was tested before and after the eight-week period.
At the end of the training period, cognitive functioning was re-assessed. Prior to training, no significant differences were found among the three groups. After the training, improved temporal information processing was found on the tone task in the temporal training group. It was accompanied by improvements in some aspects of attention and short-term memory. In contrast, the non-temporal training group’s attentional and memory resources scores remained at the pre-training level, while only the second measure of temporal information processing improved. Changes in the control group were nonsignificant.
The temporal training group was tested again 18 months after the training completion. The positive effects remained stable. TIP, divided attention, matching complex patterns, and working memory span remained at a similar level as in the post-training assessment. Although vigilance of attention declined from the post-training assessment, for all measures the results were not worse than in the pre-training assessment. “Although FFW does not train other cognitive functions directly, attention and short-term memory resources were necessary to perform the training tasks correctly,” explain Professor Szelag and Dr Skolimowska. “To succeed in the FFW games, the temporal skills had to be accompanied by efficient basic cognitive processes.”
Professor Szelag concludes, “These results show a new impact of temporal training on age-related cognitive decline in the senior population. Moreover, they foster a greater understanding of the relationships between timing and cognition, and they show new possibilities for the application of temporal training.” On the basis of these results the Laboratory of Neuropsychology has recently initiated an innovative rehabilitation computer program that addresses improvement of a broad range of cognitive functions in children and adults.
Posted: 19 Aug 2012 09:00 PM PDT
What comes naturally to most people ? to think and then do ? is difficult for stroke patients who have lost the full use of their limbs. New research by Rice University, the University of Houston (UH) and TIRR Memorial Hermann aims to help victims recover that ability to the fullest extent possible with a $1.17 million grant from the National Institutes of Health (NIH) and the President’s National Robotics Initiative (NRI).
The multidisciplinary team hopes to develop and validate a noninvasive brain-machine interface (BMI) to a robotic orthotic device that is expected to innovate upper-limb rehabilitation. The new neurotechnology will interpret brain waves that let a stroke patient willingly operate an exoskeleton that wraps around the arm from the fingertips to the elbow.
Rice is developing the exoskeleton and UH the electroencephalograph-based (EEG) neural interface. The combined device will be validated by UTHealth physicians at TIRR Memorial Hermann with as many as 40 volunteer patients in the final two years of the four-year R01 award, the oldest research grant offered by NIH. The grant, funded through the National Institute of Neurological Disorders and Stroke, is one of only a few projects selected by the NRI, a collaborative partnership by the NIH, National Science Foundation, NASA and the Department of Agriculture to encourage the development of the next generation of robots that will work closely with humans.
Repetitive motion has proven effective at retraining motor nerve pathways damaged by a stroke, but patients must be motivated to do the work, said principal investigator Marcia O’Malley, an associate professor of mechanical engineering and materials science at Rice and director of Rice’s Mechatronics and Haptic Interfaces Lab.
“With a lot of robotics, if you want to engage the patient, the robot has to know what the patient is doing,” O’Malley said. “If the patient tries to move, the robot has to anticipate that and help. But without sophisticated sensing, the patient has to physically move ? or initiate some movement.”
The team led by José Luis Contreras-Vidal, director of UH’s Laboratory for Noninvasive Brain-Machine Interface Systems and a professor of electrical and computer engineering, was the first to successfully reconstruct 3-D hand and walking movements from brain signals recorded in a noninvasive way using an EEG brain cap. The technology allows users to control, with their thoughts, robotic legs and below-elbow amputees to control neuroprosthetic limbs. The new project will be one of the first to design a BMI system for stroke survivors.
Initially, EEG devices will translate brain waves from healthy subjects into control outputs to operate the MAHI-EXO II robot, and then from stroke survivors who have some ability to initiate movements, to prompt the robot into action. That will allow the team to refine the EEG-robot interface before moving to a clinical population of stroke patients with no residual upper-limb function.
When set into motion, the intelligent exoskeleton will use thoughts to trigger repetitive motions and retrain the brain’s motor networks. An earlier version of the MAHI-EXO II developed by O’Malley, already in validation trials to rehabilitate spinal-cord-injury patients at the UTHealth Motor Recovery Lab at TIRR Memorial Hermann, incorporates sophisticated feedback that allows the patient to work as hard as possible while gently assisting ? and sometimes resisting ? movement to build strength and accuracy.
“The capability to harness a user’s intent through the EEG neural interface to control robots makes it possible to fully engage the patient during rehabilitation,” Contreras-Vidal said. “Putting the patient directly in the ‘loop’ is expected to accelerate motor learning and improve motor performance. The EEG technology will also provide valuable real-time assessments of plasticity in brain networks due to the robot intervention ? critical information for reverse engineering of the brain.”
The three institutions bring unique perspectives to the project, O’Malley said. Rice’s robotic devices and UH’s neural interfaces will make it possible for TIRR Memorial Hermann, led by Gerard Francisco, director of the UTHealth Motor Recovery Lab, to facilitate translational research to fast-track engineering findings into clinical practice.
“This is truly an outstanding opportunity to demonstrate how various technological advances can potentially boost traditional rehabilitation therapies,” said Francisco, chief medical officer of TIRR Memorial Hermann and professor and chairman of physical medicine and rehabilitation at UTHealth. “What makes this initiative even more exciting is that the NRI recognized the value of our collaborative effort by awarding the this grant to multiple principal investigators. This project will be among the first to investigate the benefits of combined therapeutic interventions to help stroke survivors.”
This release is available online at http://news.rice.edu/2012/08/20/brain-wave-reading-robot-might-help-stroke-patients-2/
Mechatronics and Haptic Interfaces Lab: http://mahilab.rice.edu/
Non-Invasive Brain Machine Interface Systems Laboratory: http://www2.egr.uh.edu/~catrenad/index.html
TIRR Memorial Hermann: http://www.memorialhermann.org/locations/tirr/
Image for download:
From left, Gerard Francisco, José Luis Contreras-Vidal and Marcia O’Malley work with a University of Houston (UH) graduate student testing MAHI-EXO II, a robotic rehabilitation device developed at Rice and being used at TIRR Memorial Hermann to help spinal-cord-injury patients recover. In a new project, a similar device will be matched with a noninvasive neural interface under development at UH to help rehabilitate stroke survivors. (Credit: Bruce French/TIRR Memorial Hermann)
Rice University contacts:
University of Houston contact:
TIRR Memorial Hermann contact:
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