Posts tagged medicine
Articles and news from the latest research reports.
Artificial Sweetener a Potential Treatment for Parkinson’s Disease
TAU researcher says mannitol could prevent aggregation of toxic proteins in the brain
Mannitol, a sugar alcohol produced by fungi, bacteria, and algae, is a common component of sugar-free gum and candy. The sweetener is also used in the medical field — it’s approved by the FDA as a diuretic to flush out excess fluids and used during surgery as a substance that opens the blood/brain barrier to ease the passage of other drugs.
Now Profs. Ehud Gazit and Daniel Segal of Tel Aviv University’s Department of Molecular Microbiology and Biotechnology and the Sagol School of Neuroscience, along with their colleague Dr. Ronit Shaltiel-Karyo and PhD candidate Moran Frenkel-Pinter, have found that mannitol also prevents clumps of the protein α-synuclein from forming in the brain — a process that is characteristic of Parkinson’s disease.
These results, published in the Journal of Biological Chemistry and presented at the Drosophila Conference in Washington, DC in April, suggest that this artificial sweetener could be a novel therapy for the treatment of Parkinson’s and other neurodegenerative diseases. The research was funded by a grant from the Parkinson’s Disease Foundation and supported in part by the Lord Alliance Family Trust.
Seeing a significant difference
After identifying the structural characteristics that facilitate the development of clumps of α-synuclein, the researchers began to hunt for a compound that could inhibit the proteins’ ability to bind together. In the lab, they found that mannitol was among the most effective agents in preventing aggregation of the protein in test tubes. The benefit of this substance is that it is already approved for use in a variety of clinical interventions, Prof. Segal says.
Next, to test the capabilities of mannitol in the living brain, the researchers turned to transgenic fruit flies engineered to carry the human gene for α-synuclein. To study fly movement, they used a test called the “climbing assay,” in which the ability of flies to climb the walls of a test tube indicates their locomotive capability. In the initial experimental period, 72 percent of normal flies were able to climb up the test tube, compared to only 38 percent of the genetically-altered flies.
The researchers then added mannitol to the food of the genetically-altered flies for a period of 27 days and repeated the experiment. This time, 70 percent of the mutated flies could climb up the test tube. In addition, the researchers observed a 70 percent reduction in aggregates of α-synuclein in mutated flies that had been fed mannitol, compared to those that had not.
These findings were confirmed by a second study which measured the impact of mannitol on mice engineered to produce human α-synuclein, developed by Dr. Eliezer Masliah of the University of San Diego. After four months, the researchers found that the mice injected with mannitol also showed a dramatic reduction of α-synuclein in the brain.
Delivering therapeutic compounds to the brain
The researchers now plan to re-examine the structure of the mannitol compound and introduce modifications to optimize its effectiveness. Further experiments on animal models, including behavioral testing, whose disease development mimics more closely the development of Parkinson’s in humans is needed, Prof. Segal says.
For the time being, mannitol may be used in combination with other medications that have been developed to treat Parkinson’s but which have proven ineffective in breaking through the blood/brain barrier, says Prof. Segal. These medications may be able to “piggy-back” on mannitol’s ability to open this barrier into the brain.
Although the results look promising, it is still not advisable for Parkinson’s patients to begin ingesting mannitol in large quantities, Prof. Segal cautions. More testing must be done to determine dosages that would be both effective and safe.
(Source: aftau.org)
Researchers Develop Novel Drug That Reverses Loss of Brain Connections in Models of Alzheimer’s
The first experimental drug to boost brain synapses lost in Alzheimer’s disease has been developed by researchers at Sanford-Burnham Medical Research Institute. The drug, called NitroMemantine, combines two FDA-approved medicines to stop the destructive cascade of changes in the brain that destroys the connections between neurons, leading to memory loss and cognitive decline.
The decade-long study, led by Stuart A. Lipton, M.D., Ph.D., professor and director of the Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, who is also a practicing clinical neurologist, shows that NitroMemantine can restore synapses, representing the connections between nerve cells (neurons) that have been lost during the progression of Alzheimer’s in the brain. The research findings are described in a paper published June 17 by the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
The focus on a downstream target to treat Alzheimer’s, rather than on amyloid beta plaques and neurofibrillary tangles—approaches which have shown little success—“is very exciting because everyone is now looking for an earlier treatment of the disease,” Lipton said. “These findings actually mean that you might be able to intercede not only early but also a bit later.” And that means that an Alzheimer’s patient may be able to have synaptic connections restored even with plaques and tangles already in his or her brain.
Targeting lost synapses
In their study, conducted in animal models as well as brain cells derived from human stem cells, Lipton and his team mapped the pathway that leads to synaptic damage in Alzheimer’s. They found that amyloid beta peptides, which were once thought to injure synapses directly, actually induce the release of excessive amounts of the neurotransmitter glutamate from brain cells called astrocytes that are located adjacent to the nerve cells.
Normal levels of glutamate promote memory and learning, but excessive levels are harmful. In patients suffering from Alzheimer’s disease, excessive glutamate activates extrasynaptic receptors, designated eNMDA receptors (NMDA stands for N-methyl-D-aspartate), which get hyperactivated and in turn lead to synaptic loss.
How NitroMemantine works
Lipton’s lab had previously discovered how a drug called memantine can be targeted to eNMDA receptors to slow the hyperactivity seen in Alzheimer’s. This patented work contributed to the FDA approval of memantine in 2003 for the treatment of moderate to severe Alzheimer’s disease. However, memantine’s effectiveness has been limited. The reason, the researchers found, was that memantine—a positively charged molecule—is repelled by a similar charge inside diseased neurons; therefore, memantine gets repelled from its intended eNMDA receptor target on the neuronal surface.
In their study, the researchers found that a fragment of the molecule nitroglycerin—a second FDA-approved drug commonly used to treat episodes of chest pain or angina in people with coronary heart disease—could bind to another site that the Lipton group discovered on NMDA receptors. The new drug represents a novel synthesis connecting this fragment of nitroglycerin to memantine, thus representing two FDA-approved drugs connected together. Because memantine rather selectively binds to eNMDA receptors, it also functions to target nitroglycerin to the receptor. Therefore, by combining the two, Lipton’s lab created a new, dual-function drug. The researchers developed 37 derivatives of the combined drug before they found one that worked, Lipton said.
By shutting down hyperactive eNMDA receptors on diseased neurons, NitroMemantine restores synapses between those neurons. “We show in this paper that memantine’s ability to protect synapses is limited,” Lipton said, “but NitroMemantine brings the number of synapses all the way back to normal within a few months of treatment in mouse models of Alzheimer’s disease. In fact, the new drug really starts to work within hours.”
To date, therapies that attack amyloid plaques and neurofibrillary tangles have failed. “It’s quite disappointing because I see really sick patients with dementia. However, I’m now optimistic that NitroMemantine will be effective as we advance to human trials, bringing new hope to both early and later-stage Alzheimer’s patients,” Lipton said.
Changing gut bacteria through diet affects brain function
UCLA researchers now have the first evidence that bacteria ingested in food can affect brain function in humans. In an early proof-of-concept study of healthy women, they found that women who regularly consumed beneficial bacteria known as probiotics through yogurt showed altered brain function, both while in a resting state and in response to an emotion-recognition task.
The study, conducted by scientists with the Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress, part of the UCLA Division of Digestive Diseases, and the Ahmanson–Lovelace Brain Mapping Center at UCLA, appears in the current online edition of the peer-reviewed journal Gastroenterology.
The discovery that changing the bacterial environment, or microbiota, in the gut can affect the brain carries significant implications for future research that could point the way toward dietary or drug interventions to improve brain function, the researchers said.
"Many of us have a container of yogurt in our refrigerator that we may eat for enjoyment, for calcium or because we think it might help our health in other ways," said Dr. Kirsten Tillisch, an associate professor of medicine in the digestive diseases division at UCLA’s David Geffen School of Medicine and lead author of the study. "Our findings indicate that some of the contents of yogurt may actually change the way our brain responds to the environment. When we consider the implications of this work, the old sayings ‘you are what you eat’ and ‘gut feelings’ take on new meaning."
Researchers have known that the brain sends signals to the gut, which is why stress and other emotions can contribute to gastrointestinal symptoms. This study shows what has been suspected but until now had been proved only in animal studies: that signals travel the opposite way as well.
"Time and time again, we hear from patients that they never felt depressed or anxious until they started experiencing problems with their gut," Tillisch said. "Our study shows that the gut–brain connection is a two-way street."
The small study involved 36 women between the ages of 18 and 55. Researchers divided the women into three groups: one group ate a specific yogurt containing a mix of several probiotics — bacteria thought to have a positive effect on the intestines — twice a day for four weeks; another group consumed a dairy product that looked and tasted like the yogurt but contained no probiotics; and a third group ate no product at all.
Functional magnetic resonance imaging (fMRI) scans conducted both before and after the four-week study period looked at the women’s brains in a state of rest and in response to an emotion-recognition task in which they viewed a series of pictures of people with angry or frightened faces and matched them to other faces showing the same emotions. This task, designed to measure the engagement of affective and cognitive brain regions in response to a visual stimulus, was chosen because previous research in animals had linked changes in gut flora to changes in affective behaviors.
The researchers found that, compared with the women who didn’t consume the probiotic yogurt, those who did showed a decrease in activity in both the insula — which processes and integrates internal body sensations, like those from the gut — and the somatosensory cortex during the emotional reactivity task.
Further, in response to the task, these women had a decrease in the engagement of a widespread network in the brain that includes emotion-, cognition- and sensory-related areas. The women in the other two groups showed a stable or increased activity in this network.
During the resting brain scan, the women consuming probiotics showed greater connectivity between a key brainstem region known as the periaqueductal grey and cognition-associated areas of the prefrontal cortex. The women who ate no product at all, on the other hand, showed greater connectivity of the periaqueductal grey to emotion- and sensation-related regions, while the group consuming the non-probiotic dairy product showed results in between.
The researchers were surprised to find that the brain effects could be seen in many areas, including those involved in sensory processing and not merely those associated with emotion, Tillisch said.
The knowledge that signals are sent from the intestine to the brain and that they can be modulated by a dietary change is likely to lead to an expansion of research aimed at finding new strategies to prevent or treat digestive, mental and neurological disorders, said Dr. Emeran Mayer, a professor of medicine (digestive diseases), physiology and psychiatry at the David Geffen School of Medicine at UCLA and the study’s senior author.
"There are studies showing that what we eat can alter the composition and products of the gut flora — in particular, that people with high-vegetable, fiber-based diets have a different composition of their microbiota, or gut environment, than people who eat the more typical Western diet that is high in fat and carbohydrates," Mayer said. "Now we know that this has an effect not only on the metabolism but also affects brain function."
The UCLA researchers are seeking to pinpoint particular chemicals produced by gut bacteria that may be triggering the signals to the brain. They also plan to study whether people with gastrointestinal symptoms such as bloating, abdominal pain and altered bowel movements have improvements in their digestive symptoms which correlate with changes in brain response.
Meanwhile, Mayer notes that other researchers are studying the potential benefits of certain probiotics in yogurts on mood symptoms such as anxiety. He said that other nutritional strategies may also be found to be beneficial.
By demonstrating the brain effects of probiotics, the study also raises the question of whether repeated courses of antibiotics can affect the brain, as some have speculated. Antibiotics are used extensively in neonatal intensive care units and in childhood respiratory tract infections, and such suppression of the normal microbiota may have long-term consequences on brain development.
Finally, as the complexity of the gut flora and its effect on the brain is better understood, researchers may find ways to manipulate the intestinal contents to treat chronic pain conditions or other brain related diseases, including, potentially, Parkinson’s disease, Alzheimer’s disease and autism.
Answers will be easier to come by in the near future as the declining cost of profiling a person’s microbiota renders such tests more routine, Mayer said.
(Source: newsroom.ucla.edu)
Pendulum Swings Back on 350-Year-Old Mathematical Mystery
A 350-year-old mathematical mystery could lead toward a better understanding of medical conditions like epilepsy or even the behavior of predator-prey systems in the wild, University of Pittsburgh researchers report.
The mystery dates back to 1665, when Dutch mathematician, astronomer, and physicist Christiaan Huygens, inventor of the pendulum clock, first observed that two pendulum clocks mounted together could swing in opposite directions. The cause was tiny vibrations in the beam caused by both clocks, affecting their motions.
The effect, now referred to by scientists as “indirect coupling,” was not mathematically analyzed until nearly 350 years later, and deriving a formula that explains it remains a challenge to mathematicians still. Now, Pitt professors apply this principle to measure the interaction of “units”—such as neurons, for example—that turn “off” and “on” repeatedly. Their findings are highlighted in the latest issue of Physical Review Letters.
“We have developed a mathematical approach to better understanding the ‘ingredients’ in a system that affect synchrony in a number of medical and ecological conditions,” said Jonathan E. Rubin, coauthor of the study and professor in Pitt’s Department of Mathematics within the Kenneth P. Dietrich School of Arts and Sciences. “Researchers can use our ideas to generate predictions that can be tested through experiments.”
More specifically, the researchers believe the formula could lead toward a better understanding of conditions like epilepsy, in which neurons become overly active and fail to turn off, ultimately leading to seizures. Likewise, it could have applications in other areas of biology, such as understanding how bacteria use external cues to synchronize growth.
Together with G. Bard Ermentrout, University Professor of Computational Biology and professor in Pitt’s Department of Mathematics, and Jonathan J. Rubin, an undergraduate mathematics major, Jonathan E. Rubin examined these forms of indirect communication that are not typically included in most mathematical studies owing to their complicated elements. In addition to studying neurons, the Pitt researchers applied their methods to a model of artificial gene networks in bacteria, which are used by experimentalists to better understand how genes function.
“In the model we studied, the genes turn off and on rhythmically. While on, they lead to production of proteins and a substance called an autoinducer, which promotes the genes turning on,” said Jonathan E. Rubin. “Past research claimed that this rhythm would occur simultaneously in all the cells. But we show that, depending on the speed of communication, the cells will either go together or become completely out of synch with each another.”
To apply their formula to an epilepsy model, the team assumed that neurons oscillate, or turn off and on in a regular fashion. Ermentrout compares this to Southeast Asian fireflies that flash rhythmically, encouraging synchronization.
“For neurons, we have shown that the slow nature of these interactions encouraged ‘asynchrony,’ or firing at different parts of the cycle,” Ermentrout said. “In these seizure-like states, the slow dynamics that couple the neurons together are such that they encourage the neurons to fire all out of phase with each other.”
The Pitt researchers believe this approach may extend beyond medical applications into ecology—for example, a situation in which two independent animal groups in a common environment communicate indirectly. Jonathan E. Rubin illustrates the idea by using a predator-prey system, such as rabbits and foxes.
“With an increase in rabbits will come an increase in foxes, as they’ll have plenty of prey,” said Jonathan E. Rubin. “More rabbits will get eaten, but eventually the foxes won’t have enough to eat and will die off, allowing the rabbit numbers to surge again. Voila, it’s an oscillation. So, if we have a fox-rabbit oscillation and a wolf-sheep oscillation in the same field, the two oscillations could affect each other indirectly because now rabbits and sheep are both competing for the same grass to eat.”
(Source: news.pitt.edu)
Loyola surgeon using electrical stimulation to speed recovery in Bell’s palsy patients
A Loyola University Medical Center surgeon is using electrical stimulation as part of an advanced surgical technique to treat Bell’s palsy. Bell’s palsy is a condition that causes paralysis on one side of a patient’s face.
During surgery, Dr. John Leonetti stimulates the patient’s damaged facial nerve with an electric current, helping to jump-start the nerve in an effort to restore improved facial movement more quickly.
Leonetti said some patients who have received electrical stimulation have seen muscle movement return to their face after one or two months — rather than the four-to-six months it typically takes for movement to return following surgery.
A virus triggered Bell’s palsy in Audrey Rex, 15, of Lemont, Ill. Her right eye could not close and her smile was lopsided, making her feel self-conscious. She had to drink from a straw, and eating was frustrating - she would accidently bite her bottom lip when it got stuck on her teeth.
She was treated with steroids, but after six weeks, there were no improvements. So Audrey’s mother did further research and made an appointment with Leonetti, and he recommended surgery with electrical stimulation, followed by physical therapy. Today, Audrey’s appearance has returned to normal, and she has regained nearly all of the facial muscle movements she had lost.
“I feel very blessed that we were referred to Dr. Leonetti,” said Deborah Rex, Audrey’s mother.
Bell’s palsy is classified as an idiopathic disorder, meaning its cause is not definitely known. However, most physicians believe Bell’s palsy is caused by a viral-induced swelling of the facial nerve within its bony covering. Symptoms include paralysis on one side of the face; inability to close one eye; drooling; dryness of the eye; impaired taste; and a complete inability to express emotion on one side of the face.
Bell’s palsy occurs when the nerve that controls muscles on one side of the face becomes swollen, inflamed or compressed. The nerve runs through a narrow, bony canal called the Fallopian canal. Following a viral infection, the nerve swells inside the canal, restricting the flow of blood and oxygen to nerve cells.
Most cases can be successfully treated with oral steroids, and 85 percent of patients experience good recovery within a month. But if symptoms persist for longer than a month, the patient may need surgery, Leonetti said. If surgery is delayed for longer than three months, the nerve damage from Bell’s palsy can be permanent. Thus, the optimal window for surgery is between one and three months after onset of symptoms.
The surgery is called microscopic decompression of the facial nerve. The surgeon removes the bony covering of the facial nerve, then slits open the outer covering of the nerve. This gives the nerve room to swell. In addition to this standard procedure, Leonetti uses an electric stimulator to send a current through the nerve. This jump starts the nerve to speed its recovery.
Decompression of the facial nerve is an established technique for treating Bell’s palsy, and electric stimulation is an established technique used in other surgeries involving the nerve. “We are combining two standard treatments to create an exceptional treatment,” Leonetti said.
Following surgery, Audrey worked with Loyola physical therapist Lisa Burkman, who used a mirror and biofeedback to teach Audrey individualized exercises of her mouth, eye, forehead, cheek and chin. Leonetti said Audrey’s case illustrates that the road back from Bell’s palsy is a multidisciplinary effort that involves the surgeon, physical therapist and patient.
A path to lower-risk painkillers: Newly-discovered drug target paves way for alternatives to morphine
New findings provide vital step towards exploring pain medications that may lower risks of prescription drug abuse and side effects of painkillers
For patients managing cancer and other chronic health issues, painkillers such as morphine and Vicodin are often essential for pain relief. The body’s natural tendency to develop tolerance to these medications, however, often requires patients to take higher doses – increasing risks of harmful side effects and dependency.
Now, new research from the University of Michigan Health System and a major pharmaceutical company has identified a novel approach to moderate and severe pain therapy that paves the way for lower dosage painkillers. The findings appear in Proceedings of the National Academy of Sciences of the United States of America.
Drugs such as hydrocodone (the main ingredient of Vicodin) and oxycodone (Oxycontin) are often the best options for the treatment of moderate to severe pain for patients facing medical conditions ranging from a wisdom tooth extraction to cancer. The drugs bind to specific molecules (opioid receptors) on nerve cells in the brain and spinal cord to prevent the feeling of pain.
“We have for the first time discovered compounds that bind to an alternative site on the nerve opioid receptors and that have significant potential to enhance the drug’s positive impact without increasing negative side effects,” says co-author John Traynor, Ph.D., professor of pharmacology at the U-M Medical School.
“We are still in the very early stages of this research with a long way to go, but we believe identifying these compounds is a key step in revolutionizing the treatment of pain. This opens the door to developing pain relief medications that require lower doses to be effective, helping address the serious issues of tolerance and dependence that we see with conventional pain therapy.”
Conventional drug treatments for pain work by targeting the so-called orthosteric site of the opioid receptor that provides pain relief. Targeting this site, however, is a double-edged sword because it is also responsible for all of the drug’s unwanted side effects, such as constipation and respiratory depression. Tolerance also limits chronic use of the drugs because higher doses are required to maintain the same effect.
Using cell systems and mouse brain membranes, researchers have identified compounds that bind to a physically distinct and previously unknown “allosteric” site on the opioid receptor- a site that fine-tunes the activity of the receptor. Not only do these compounds act at a location that hasn’t been studied as a drug target before but they bind to the receptor in a new way to enhance the actions of morphine – which means lower doses can have the same impact.
“The newly-discovered compounds bind to the same receptor as morphine but appear to act at a separate novel site on the receptor and therefore can produce different effects. What’s particularly exciting is that these compounds could potentially work with the body’s own natural painkillers to manage pain,” Traynor says.
“We know that conventional strong pain medications ultimately increase the risk of withdrawal symptoms and addiction, which is an especially serious issue with the current prescription drug abuse epidemic in our country. The implications of this work, if it translates to animal studies and then to humans, are highly significant to this area of study.”
(Source: uofmhealth.org)
Unusual Antibodies in Cows Suggest New Ways to Make Therapies for People
Humans have been raising cows for their meat, hides and milk for millennia. Now it appears that the cow immune system also has something to offer. A new study led by scientists from The Scripps Research Institute (TSRI) focusing on an extraordinary family of cow antibodies points to new ways to make human medicines.
“These antibodies’ structure and their mechanism for creating diversity haven’t been seen before in other animals’ antibodies,” said Vaughn V. Smider, assistant professor of cell and molecular biology at TSRI and principal investigator for the study, which appears as the cover story in the June 6, 2013 issue of the journal Cell.
Big Multiple Sclerosis Breakthrough
Phase 1 trial safely resets patients’ immune systems, reduces attack on myelin protein
A phase 1 clinical trial for the first treatment to reset the immune system of multiple sclerosis (MS) patients showed the therapy was safe and dramatically reduced patients’ immune systems’ reactivity to myelin by 50 to 75 percent, according to new Northwestern Medicine research.
In MS, the immune system attacks and destroys myelin, the insulating layer that forms around nerves in the spinal cord, brain and optic nerve. When the insulation is destroyed, electrical signals can’t be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness.
“The therapy stops autoimmune responses that are already activated and prevents the activation of new autoimmune cells,” said Stephen Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. “Our approach leaves the function of the normal immune system intact. That’s the holy grail.”
Miller is the co-senior author of a paper on the study, which was published June 5 in the journal Science Translational Medicine. The study is a collaboration between Northwestern’s Feinberg School, University Hospital Zurich in Switzerland and University Medical Center Hamburg-Eppendorf in Germany.
The human trial is the translation of more than 30 years of preclinical research in Miller’s lab.
In the trial, the MS patients’ own specially processed white blood cells were used to stealthily deliver billions of myelin antigens into their bodies so their immune systems would recognize them as harmless and develop tolerance to them.
Current therapies for MS suppress the entire immune system, making patients more susceptible to everyday infections and higher rates of cancer.
While the trial’s nine patients — who were treated in Hamburg, Germany — were too few to statistically determine the treatment’s ability to prevent the progression of MS, the study did show patients who received the highest dose of white blood cells had the greatest reduction in myelin reactivity.
The primary aim of the study was to demonstrate the treatment’s safety and tolerability. It showed the intravenous injection of up to 3 billion white blood cells with myelin antigens caused no adverse affects in MS patients. Most importantly, it did not reactivate the patients’ disease and did not affect their healthy immunity to real pathogens.
As part of the study, researchers tested patients’ immunity to tetanus because all had received tetanus shots in their lifetime. One month after the treatment, their immune responses to tetanus remained strong, showing the treatment’s immune effect was specific only to myelin.
The human safety study sets the stage for a phase 2 trial to see if the new treatment can prevent the progression of MS in humans. Scientists are currently trying to raise $1.5 million to launch the trial, which has already been approved in Switzerland. Miller’s preclinical research demonstrated the treatment stopped the progression of relapsing-remitting MS in mice.
“In the phase 2 trial we want to treat patients as early as possible in the disease before they have paralysis due to myelin damage.” Miller said. “Once the myelin is destroyed, it’s hard to repair that.”
In the trial, patients’ white blood cells were filtered out, specially processed and coupled with myelin antigens by a complex GMP manufacturing process developed by the study co-senior authors, Roland Martin, Mireia Sospedra, and Andreas Lutterotti and their team at the University Medical Center Hamburg-Eppendorf. Then billions of these dead cells secretly carrying the myelin antigens were injected intravenously into the patients. The cells entered the spleen, which filters the blood and helps the body dispose of aging and dying blood cells. During this process, the immune cells start to recognize myelin as a harmless and immune tolerance quickly develops. This was confirmed in the patients by immune assays developed and carried out by the research team in Hamburg.
This therapy, with further testing, may be useful for treating not only MS but also a host of other autoimmune and allergic diseases simply by switching the antigens attached to the cells. Previously published preclinical research by Miller showed the therapy’s effectiveness for type 1 diabetes and airway allergy (asthma) and peanut allergy.
The MS human trial relates directly to Miller’s recently published research in mice in which he used nanoparticles — rather than a patient’s white blood cells — to deliver the myelin antigen. Using a patient’s white blood cells is a costly and labor-intensive procedure. Miller’s study showed the nanoparticles, which are potentially cheaper and more accessible to a general population, could be as effective as the white blood cells as delivery vehicles. This nanoparticle technology has been licensed to Cour Pharmaceutical Development Company and is in preclinical development.
Miller’s research represents several pillars of Northwestern’s Strategic Plan by discovering new ways to treat disease in the biomedical sciences and translating those discoveries into ideas and products that make the world a better place for everyone.
(Source: northwestern.edu)
Rapid, Irregular Heartbeat May Be Linked to Problems with Memory and Thinking
People who develop a type of irregular heartbeat common in old age called atrial fibrillation may also be more likely to develop problems with memory and thinking, according to new research published in the June 5, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Problems with memory and thinking are common for people as they get older. Our study shows that on average, problems with memory and thinking may start earlier or get worse more quickly in people who have atrial fibrillation,” said study author Evan L. Thacker, PhD, of the University of Alabama at Birmingham. “This means that heart health is an important factor related to brain health.”
The study involved people age 65 and older from four communities in the United States who were enrolled in the Cardiovascular Health Study. Participants did not have a history of atrial fibrillation or stroke at the start of the study. They were followed for an average of seven years, and received a 100-point memory and thinking test every year. People who had a stroke were not included in this analysis after the stroke. Of the 5,150 participants, 552, or about 11 percent, developed atrial fibrillation during the study.
The study found that people with atrial fibrillation were more likely to experience lower memory and thinking scores at earlier ages than people with no history of atrial fibrillation. For example, from age 80 to age 85 the average score on the 100-point test went down by about 6 points for people without atrial fibrillation, but it went down by about 10 points for people with atrial fibrillation.
For participants ages 75 and older, the average rate of decline was about three to four points faster per five years of aging with atrial fibrillation compared to those without the condition.
“This suggests that on average, people with atrial fibrillation may be more likely to develop cognitive impairment or dementia at earlier ages than people with no history of atrial fibrillation,” Thacker said.
Thacker noted that scores below 78 points on the 100-point test are suggestive of dementia. People without atrial fibrillation in the study were predicted on average to score below 78 points at age 87, while people with atrial fibrillation were predicted to score below 78 points at age 85, two years earlier.
“If there is indeed a link between atrial fibrillation and memory and thinking decline, the next steps are to learn why that decline happens and how we can prevent that decline,” said Thacker.
New technique for deep brain stimulation surgery proves accurate and safe
Surgery has been used for Parkinson’s disease and familial tremors, and also shows promise for other disorders
The surgeon who more than two decades ago pioneered deep brain stimulation surgery in the United States to treat people with Parkinson’s disease and other movement disorders has now developed a new way to perform the surgery — which allows for more accurate placement of the brain electrodes and likely is safer for patients.
The success and safety of the new surgical technique could have broad implications for deep brain stimulation, or DBS, surgery into the future, as it may increasingly be used to help with a wide range of medical issues beyond Parkinson’s disease and familial tremors.
The new surgery also offers another distinct advantage: patients are asleep during the surgery, rather than being awake under local anesthesia to help surgeons determine placement of the electrodes as happens with the traditional DBS surgery.
A study detailing the new surgical technique is being published in the June 2013 edition of the Journal of Neurosurgery, and has been published online at the journal’s website.
"I think this will be how DBS surgery will be done in most cases going forward," said Kim Burchiel, M.D., F.A.C.S., chair of neurological surgery at Oregon Health & Science University and the lead author of the Journal of Neurosurgery article. “This surgery allows for extremely accurate placement of the electrodes and it’s safer. Plus patients don’t need to be awake during this surgery — which will mean many more patients who can be helped by this surgery will now be willing to consider it.”
DBS surgery was first developed in France in 1987. Burchiel was the first surgeon in North America to perform the surgery, as part of a Food and Drug Administration-approved clinical trial in 1991.
The FDA approved the surgery for “essential tremor” in 1997 and for tremors associated with Parkinson’s disease in 2002. The surgery has been performed tens of thousands of times over the last decade or so in the United States, most often for familial tremor and Parkinson’s disease. Burchiel and his team at OHSU have performed the surgery more than 750 times.
The surgery involves implanting very thin wire electrodes in the brain, connected to something like a pacemaker implanted in the chest. The system then stimulates the brain to often significantly reduce the tremors.
For most of the last two decades, the DBS patient was required to be awake during surgery, to allow surgeons to determine through monitoring the patient’s symptoms and getting other conscious patient feedback whether the electrodes were placed in the right spots in the brain.
But the traditional form of the surgery had drawbacks. Many patients who might have benefitted weren’t willing to undergo the sometimes 4 to 6 hour surgery while awake. There also is a small chance of hemorrhaging in the brain as the surgeon places or moves the electrodes to the right spot in the brain.
The new technique uses advances in brain imaging in recent years to place the electrodes more safely, and more accurately, than in traditional DBS surgery. The surgical team uses CT scanning during the surgery itself, along with an MRI of the patient’s brain before the surgery, to precisely place the electrodes in the brain, while better ensuring no hemorrhaging or complications from the insertion of the electrode.
The Journal of Neurosurgery article reported on 60 patients who had the surgery at OHSU over an 18-month period beginning in early 2011.
"What our results say is that it’s safe, that we had no hemorrhaging or complications at all — and the accuracy of the electrode placement is the best ever reported," Burchiel said.
Burchiel and his team have done another 140 or so surgeries with the new procedure since enrollment in the study ended. OHSU was the first center to pioneer the new DBS procedure, but other surgical teams across the U.S. are learning the technique at OHSU, and bringing it back to their own centers.
The positive results with the new DBS technique could have ramifications as medical researchers nationwide continue to explore possible new uses for DBS surgery. DBS surgery has shown promising results in clinical trials with some Alzheimer’s patients, with some forms of depression and even with obesity.
If the early promising results for these conditions are confirmed, the number of people who might be candidates for DBS surgery could expand greatly, Burchiel said.
The length of the new surgery for the 60 patients involved in the study was slightly longer than traditional DBS surgery. But as Burchiel and his team have developed the new surgical technique, the new DBS surgeries are usually much shorter, often taking half the time of the more traditional approach. Given that, and that the electrodes are placed more accurately and the surgery is cheaper to perform, the new DBS surgery likely will be the technique most surgeons will use in coming years, Burchiel said.
DBS surgery often helps significantly reduce tremors in patients with familial tremor and tremors and other symptoms in Parkinson’s disease. A parallel study is ongoing at OHSU to assess how symptoms of the patients have improved since their DBS surgery using this new method.
(Image: Dr Frank Gaillard)