Three Huge Changes for People with Parkinson's

Friday March 13, 2015

In 2002, when I was officially diagnosed with PD, my younger sister was on the case. Without telling me, she went to the office of a large Parkinson’s organization and sat down with an expert in the disease to find out what it would mean. She called me afterward, with encouraging news. The expert told her, “Your brother will never know the major symptoms of Parkinson’s Disease.” and went on to proclaim that there would certainly be a cure within ten years.

(I’ll wait for a minute until you gain control of your hysterical laughter and come back from your subsequent trip to the bathroom.)

(Are you back now? OK.) 

We all know how that turned out. I would be slightly miffed at the recklessness of this prophet of PD, but to be fair, this was not the only time I heard that 10-year prediction. And to be even fairer, while we have no ”cure” in hand, we have experienced a near revolution in the way we look at, and are starting to treat, Parkinson’s. 

There are three components to this change, all of which have the promise to contribute greatly to the care and everyday quality of life experienced by those of us with PD.

First, there is now possibility of Deep Brain Stimulation surgery. While the number of people that qualify for the surgery at any one moment is low, over time the number of people who undergo the operation will be quite significant. DBS is not a cure, and can introduce undesirable side effects of its own. And it is of course, brain surgery, with all the attendant risks. It only helps with the motor symptoms of Parkinson’s. But it can affect those symptoms powerfully, restoring much of a patient’s quality of life for an indefinite but clearly long period.

The second huge development is the elevation of attention paid to non-motor symptoms of PD. These are symptoms that are not movement problems. When I was diagnosed, depression, dementia, hallucination, apathy, loss of sense of smell and more, were seen as secondary to the motor problems. But many find these non-motor symptoms more onerous than motor problems. With the elevation of these concerns to front-burner status, doctors and patients are more likely to be aware of these issues and more motivated to address them. 

The greater attention we now pay to these symptoms creates opportunity to see PD more clearly. Parkinson’s Disease is much more than a failure of a small part of the brain. It doesn’t even become a brain disease until it has been at work in your gut and elsewhere for years. A true cure will require looking beyond the dopamine pathways of the deep brain. 

The final exciting development of the past decade is the discovery of the mighty role exercise can play in moderating the symptoms, and likely the course of the illness. When I was diagnosed, there was precious little to be found anywhere about the power of exercise to offer relief from PD. Now we know it can help maintain and improve balance, moderate many motor and non-motor symptoms, and likely slow disease progression, which nothing else we’ve tried seems to do.
  
Ten years is an eon to a sick person. It is just a blink of an eye to Parkinson’s Disease. I wish our progress were faster. I need it to be faster, as do millions around the world. But it is amazing what can happen in the blink of an eye.

Peter Dunlap-Shohl
NWPF Blogger

https://nwpf.org/stay-informed/blog/2015/03/three-huge-changes-for-people-with-parkinsons/

Adjusting Deep Brain Stimulation Can Ease Swallowing and Freezing of Gait in Parkinson’s

Science News

- Feb 13 2015

In people who have had deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD), lowering the stimulation settings may improve swallowing difficulties and freezing episodes when walking.  The results of the new study appear in the January 27 edition of Neurology.

DBS involves surgically implanting electrical stimulators into the brain. It is a standard therapy for people with PD who have developed fluctuations in the effectiveness of levodopa (given as Sinemet®) and disabling dyskinesias (involuntary movements), and are otherwise healthy.  Yet, even with DBS and medications, some PD symptoms remain difficult to treat.

For the new study, researchers led by Tao Xie, M.D., Ph.D., at the University of Chicago, tested the effects of decreasing the stimulation settings in seven people with advanced PD who had undergone DBS. All had DBS devices implanted on both sides of the brain in an area called the subthalamic nucleus (STN).  In addition, study participants all had “freezing” episodes that did not respond to medication or to DBS at the typical setting, 130 Hz.  Participants’ average age was 64 years, they had lived with PD on average for 13 years, and six of them were men. At the beginning of the study, while participants took their usual PD medication, the researchers tested a range of PD symptoms at three DBS settings:  1) 130 Hz; 2) 60 Hz; or 3) off.  For the next eight weeks, participants kept their DBS stimulators at the setting at which they experienced the least “freezing.”  Then all tests were repeated. 

Results

• Freezing of gait was significantly improved with DBS at 60 Hz.
• On questionnaires, study participants reported an 80 percent improvement in their ability to swallow with DBS at 60 Hz compared to 130 Hz.
• As viewed on a swallowing test (modified barium swallow study), DBS at 60 Hz reduced the frequency of aspiration (breathing in liquid when swallowing) by 57 percent compared to DBS at 130 Hz.
• For one participant, resting hand tremor worsened with DBS at 60 Hz; this participant returned to 130 Hz DBS after three weeks.
• These improvements lasted as long as DBS was set at 60 Hz.

What Does It Mean?

This study identifies a potentially simple way to reduce life-threatening risks of PD in a subset of people with advanced PD who have undergone DBS.  Making swallowing easier for people with PD is important because breathing food or liquid into the airways can lead to pneumonia. Lessening “freezing” episodes is also critical, because freezing can increase a person’s risk of falls.   

There are many parameters that can be adjusted when programming a person’s DBS stimulator, such as voltage intensity and stimulation frequency.  Standard practice has been to use a high frequency stimulation, such as 130 Hz, when adjusting DBS settings because this is the frequency studies have shown best controls movement symptoms including tremor, stiffness and slowness.

Although the study was carried out in a randomized, double-blind manner – the most rigorous type of clinical study, the number of participants was small and the duration of the study was only several weeks, therefore one should be cautious in interpreting these results.  For instance, more research is needed to determine whether lowering DBS helps swallowing in people who do not experience “freezing” and whether the benefit can last over a long term. Also, the authors note that people who have DBS to manage their tremors may not be able to reduce their stimulation level without the tremor worsening.  Nevertheless, by exploring a greater range of DBS stimulation parameters, these investigators may be able to help pave the way to a reduction in the number of complications that people experience with advanced PD and DBS.  Lastly, the study highlights an active area of basic research on novel brain circuits. Intervening on these circuits may help  treat symptoms that have been beyond the reach of current therapeutic modalities.

Reference: Xie, T., Vigil, J., MacCracken, E., Gasparaitis, A., Young, J., Kang, W., Bernard, J, Warnke, P., Kang, U.J. (2014). Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD. Neurology. doi:10.1212/WNL.0000000000001184

http://www.pdf.org/en/science_news/release/pr_1423853249

EARLY WARNING SIGNS OF PARKINSON'S DISEASE

12th March 2015 - New research

Researchers assessed the association between the first presentation of prediagnostic features and a subsequent diagnosis of Parkinson's Disease. Those symptoms considered were motor features (tremor, rigidity, balance impairments, neck pain or stiffness, and shoulder pain or stiffness), autonomic features (constipation, hypotension, erectile dysfunction, urinary dysfunction, and dizziness), neuropsychiatric disturbances (memory problems, late-onset anxiety or depression, cognitive decline, and apathy), and additional features (fatigue, insomnia, anosmia, hypersalivation and rapid-eye-movement sleep behaviour disorder).

Apathy, REM sleep disorder, anosmia, hypersalivation, and cognitive decline were excluded because they were infrequently reported. At 10 years before the diagnosis of Parkinson's disease, the prevalence of tremor was an average of 7 times more likely, and constipation was twice as likely in those people who went on to develop Parkinson's disease than in those people who did not have Parkinson 's Disease.

At 5 years before diagnosis, people who went on to develop Parkinson's Disease had a far higher prevalence of tremor (from 7 to 24 times more likely), and also had a higher likelihood (in order or likelihood) of : hypotension, constipation, balance impairments, dizziness, urinary dysfunction, depression, fatigue, anxiety and erectile dysfunction.

At 2 years before Parkinson's disease diagnosis, the prevalence of all studied prediagnostic features except neck pain or stiffness was higher in people who went on to develop Parkinson's Disease.

Reference : Lancet Neurology [2015] 14 (1) : 57-64 (A.Schrag, L.Horsfall, K.Walters, A. Noyce, I.Petersen) 

Complete abstract : http://www.ncbi.nlm.nih.gov/pubmed/25435387
http://www.viartis.net/parkinsons.disease/news/150312.pdf mail@viartis.net
©2015 Viartis 

People with “Invisible" Diseases Struggle for Resources, Understanding

FoxFeed Blog

Posted by  Nancy Ryerson, March 12, 2015

For many, Parkinson’s disease symptoms change throughout the day. You may be symptomatic in the morning, but feel — and appear — well in the afternoon. While showing symptoms can lead to negative stigma, sometimes appearing symptom-free causes its own problems.

NPR recently covered the challenges faced by people with "invisible" diseases, such as Crohn’s disease and fibromyalgia. Because they generally don’t require wheelchairs or other visual signs, people with such diseases often struggle to access needed services, and may even be denied workplace accommodations. The story explained:           

When a disability isn't immediately obvious, others — at work, school or even at home — sometimes doubt it exists and accuse those who suffer from invisible conditions of simply angling for special treatment.

While many people with Parkinson's don't consider it a disability, there are instances where accessibility becomes important. Alice Belous blogged on asking her neurologist about getting a handicapped parking permit, to which he replied that she should not because there are “people in wheelchairs who ‘really’” needed it more. Her physical therapist eventually helped convince her to apply. Since getting the permit, strangers have given her dirty looks and asked if she really needs the handicapped space when they see her in parking lots.

Groups like the Invisible Disabilities Association are working to raise awareness that not all diseases and challenges are readily visible.

"Hopefully folks will realize that there are handicaps that cannot always be easily seen or recognized,” writes Alice. “I’m just doing the best I can. Let’s just extend some grace to one another — and ourselves.”

Alice Belous is the mother of two adult children, and a poodle. She worked over fourteen years as a school librarian. Now she sells library books and ebooks for the largest book wholesaler in the U.S. and blogs at Bibmomma.

The diagnosis of Parkinson’s disease was determined before she was 50 yrs. old and as an Early Onset patient she tries to continue to be active. Alice loves to knit, nuno-felt and create items from felted wool in her spare time.

A year ago I gave in and applied for a handicap parking permit.  I feel funny using it because I want to “force” myself to walk without rigidity, but that doesn’t happen. I want to “force” myself to walk without stumbling, but that doesn’t happen either.  Like most people with Parkinson’s Disease I have good days and bad days. So far, my driving has not been affected.  I am able to respond quickly and I really don’t drive places other than the ‘hood. Everything like the bank, grocery, drug store and doctors are within a 2-5 mile radius of our home.

But I still feel strange parking in the handicap places.  So, on good days, I don’t. I park in normal spaces and walk, swinging my arms and carefully placing my feet one in front of the other. I haven’t fallen in public in a good long time.

Today we went to eat lunch and then to a “big box store”. I parked in the handicapped place next to the restaurant and when we finished we walked to the store. It was good exercise, but I was jiggling and tremoring my way through the parking lot.  Perhaps I feel guilty about having this handicap designation because my neurologist was hesitant to give it to me. He said that there were people in wheelchairs who “really” needed it more than me. But then my physical therapist intervened and told him that when I travel, or when I’m having a bad day, I really do need it – and he relented.

I hate having to rationalize Parkinson’s disease and my needs to people….most especially my doctor. And I hate being stared at in a parking lot having someone wonder, “is she really handicapped?” It makes this disease much harder to live with, much harder to deal with on a daily basis, and much harder to overcome.

Hopefully folks will realize that there are handicaps that cannot always be easily seen or recognized. I’m just doing the best I can. Let’s just extend some grace to one another – and ourselves.

Dark neural patches

(IMAGE) OKINAWA INSTITUTE OF SCIENCE AND TECHNOLOGY(OIST) GRADUATE UNIVERSITY

11-MAR-2015

The virus stains in red the connections leaving the neostriatum wherever it is expressed, but not everywhere as was expected. In the engineered mouse strain the neurons were already fluorescent and the red mixed with the green to form an orangish-yellow hue in the locality of the neostriatum. Within this orangish-yellow zone, are green 'islands' which the virus spared. These are the 'patch' cell groupings. In regular mice, these areas would be a distribution of dark patches.

Researchers at the Okinawa Institute of Science and Technology Graduate University's Brain Mechanisms for Behaviour Unit have found a surprise upon mapping the precise connectivity inside a brain structure called the neostriatum. The cell groups here do not seem to be talking to each other, and are less interdependent in their functioning than previously suspected. Their findings were published in Brain Structure and Function.

The neostriatum is part of a larger system in the brain that plans and executes voluntary movements. It consists of 'patch' and 'matrix' type neurons that are grouped separately. But these groupings still interweave in a three dimensional labyrinth. The lack of cross-talk between them revealed by this study has implications for studying diseases like Parkinson's, which afflicts the nervous system.

In a human Parkinson's patient, the neostriatum is depleted of the messenger chemical dopamine, which helps regulate and strengthen motor responses in the brain. These patients have extraordinary difficulty starting mundane activities like standing or walking. Yet they do rise to the occasion during emergencies, and sometimes even find stairs easier. This is a neuro-scientific puzzle.

The OIST researchers who published the findings study Parkinson's in mice. They initially infected all the outputs leaving the neostriatum, with a virus that makes the cells sensitive to light. They expected all the connections to fire and the cells to light up in the neostriatum upon stimulating the brain slices. But to their surprise, some parts didn't.

At this point, the experienced eye of the OIST unit's head Prof. Gordon Arbuthnott recognized the distribution of these dark patches as the 'patch' cell compartments he had helped map years earlier. The virus had spared them. This fortuitous finding now allowed the researchers to stimulate the 'patch' and 'matrix' compartments separately. They could find no active connections between the two areas.

To find a behavioral link in mice, OIST researchers first trained hungry mice to reach for food pellets, then used the virus to temporarily deactivate all matrix compartments in a sub-part of the neostriatum that had been previously associated with forepaw use.

With only 'patch' cells at their disposal the mice failed to grasp the pellets, but kept reaching for them. Consistent failure did not discourage them, as it would healthy mice.

While the overall finding confirms older anatomical speculations about the 'patch' and 'matrix' groupings being independent, Prof. Arbuthnott is not entirely convinced.

The result opens new avenues for studying the neostriatum. While most research over the past decade has focused on mapping connections leaving it, the OIST result is a gentle nudge in the right direction - inward, not outward.

"The simplest level of explanation I can think of is that one part makes the value judgment based on previous experience, and the other controls the movement. But is it really true that one part is doing one kind of calculation without consulting the other part? That's the big question for me," he said.

###

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

http://health.einnews.com/article/254272666/ad2BC4gVezhHGNyn

U of R helps develop Parkinson's app

Updated: Tuesday, March 10 2015, 10:48 PM EDT Rochester, N.Y. - 

A new app that helps Parkinson's Disease patients has been developed with help from researchers at the University of Rochester. The app, called mPower, is only hours old and already has thousands of downloads. It's part of a large research project being conducted at the university. For the first time, the app allows Parkinson's patients to share their symptoms with researchers while also getting to see real-time results themselves. The app is designed to measure dexterity, balance and gait, voice and memory multiple times a day. We can bring about greater collaboration with greater accuracy, but compress the time frame so in that sense it's a very powerful tool," said patient Gary Hilburger. "I really look forward to being able to participate in this study and help out in whatever way I can." "We hope to also understand how the disease changes over the course of time to get better sense of the disease itself and to identify factors, whether disease, diet, exercise or other factors that patients tell us is making their symptoms better or worse," said Dr. Ray Dorsey, M.D., MBA and Professor of Neurology. The app will allow researchers to gain greater insight into the disease. Right now, it is only available for download in the Apple App Store.

Read More at: http://13wham.com//news/features/top-stories/stories/u-r-helps-develop-parkinsons-app-20824.shtml

Exploring Sexual Dysfunction in Parkinson's

FoxFeed Blog

Posted by  Rachel Dolhun, MD, March 11, 2015

There’s no shame in sexual dysfunction

As with any subject that makes us the least bit embarrassed, sexual dysfunction is often swept under the rug. It is seldom mentioned outside the bedroom and rarely, if ever, brought up to (or by) one’s neurologist.  Still, sexual disturbances are a common part of getting older and occur frequently among people with Parkinson’s disease (PD). A candid essay by longtime Foundation friend Marc Jaffe opens the door to conversations surrounding this complex topic.

In Sunday’s Modern Love column in The New York Times, Marc writes about “Finding Equilibrium in Seesawing Libidos.” As a man in a 15-year marriage, he was frustratingly aware of how mismatched the two genders’ sex drives can be and how this dichotomy only seems to grow with time. So, when his wife Karen was diagnosed with Parkinson’s and prescribed medication with a side effect of hypersexuality, you’d imagine it was “problem solved” (with regard to the sexual divide, at least). And it was — temporarily — until the pendulum swung in the opposite direction and Karen’s insatiable appetite drove Marc to stop-gap measures like taking prescription drugs simply to keep up.

Eventually, Karen was able to find another outlet and she now channels the majority of her energy into fundraising and advocating for Parkinson’s research. [In fact, she’s a member of our Patient Council.] Doing so has allowed her and Marc to settle back into a comfortable partnership — one that still has unequal, but no longer incompatible, sexual desires.

The hypersexuality Karen experienced in response to the prescribed dopamine agonist is just one possible form of the sexual disturbances that can be seen in Parkinson’s disease. 

Sexual dysfunction is common in Parkinson’s

Parkinson’s contributes to sexual dysfunction through physical, psychological and pharmacological effects.

• Fatigue, bradykinesia and rigidity can make sexual activity more challenging. Tremor and dyskinesia can cause discomfort, especially as these symptoms naturally increase with excitement.
• Depression, often associated with PD, can lessen sex drive. Body image issues, shifting roles and changes in appearance secondary to Parkinson’s are additional mental factors.
• Parkinson’s medications and antidepressants can influence libido. Dopamine agonists are notorious for causing hypersexuality.

Sexual matters are infrequently addressed and are therefore inadequately treated. As a result, symptoms unnecessarily interfere with a healthy sexual relationship and impair quality of life.

Multiple treatment options are available 

If your doctor does not routinely inquire about sexual problems, you may have to raise the subject yourself. A myriad of options exists to manage sexual dysfunction, but none of them can be offered if your doctor is unaware of your concerns. Your neurologist will work with you to develop an individualized treatment plan but there are some general guidelines to follow:

• Schedule sexual activity for times when medication is typically working optimally.
• Experiment with other types of foreplay and sexual positions to find what works. Look for ways to express affection in manners aside from sexual intercourse.
• Ask your doctor about prescription medications to manage specific problems like erectile dysfunction or vaginal dryness. Request referral to a urologist or gynecologist if your neurologist is not comfortable managing these symptoms.
• Don’t be embarrassed to discuss hypersexuality with your physician. This may signal the need to decrease the dosage of or discontinue dopamine agonists.
• Maintain an honest and ongoing dialogue with your partner. Together you can scheme up ways around Parkinson’s. If this proves too difficult, consider enlisting the help of a therapist or counselor who can mediate your discussions.

Marc says, “It is understood that when one spouse gets Parkinson’s, the other spouse will be affected by it.” While this is certainly true, the magnitude of Parkinson’s effect on both people can be dampened. As with every aspect of a relationship, open communication is crucial to handling changes in sexual desire or function resulting from Parkinson’s and its treatment. Through trial and error in managing challenging circumstances as they arise, you and your significant other will adapt and find a balance that suits you both.

* NOTE: The medical information contained in this article is for general information purposes only. The Michael J. Fox Foundation has a policy of refraining from advocating, endorsing or promoting any drug therapy, course of treatment, or specific company or institution. It is crucial that care and treatment decisions related to Parkinson’s disease and any other medical condition be made in consultation with a physician or other qualified medical professional.

Mad Cow Research Hints At Ways To Halt Alzheimer's, Parkinson's

Prion protein can be infectious, spreading from cell to cell in the brain. Here four nerve cells in a mouse illustrate how infectious prion protein moves within cells along neurites — wire-like connections the nerve cells use for communicating with adjacent cells.

Alzheimer's, Parkinson's and amyotrophic lateral sclerosis ravage the brain in very different ways. But they have at least one thing in common, says Corinne Lasmezas, a neuroscientist and professor at Scripps Research Institute, in Jupiter, Fla. Each spreads from brain cell to brain cell like an infection.

"So if we could block this [process], that might prevent the diseases," Lasmezas says.

It's an idea that's being embraced by a growing number of researchers these days, including Nobel laureate Dr. Stanley Prusiner, who first recognized in the 1980s the infectious nature of brain proteins that came to be called prions. But the idea that mad cow prions could cause disease in people has its origins in an epidemic of mad cow disease that occurred in Europe and the U.K. some 15 years ago.

Back then, Lasmezas was a young researcher in France studying how mad cow, formally known as bovine spongiform encephalopathy, was transmitted. "At that time, nobody knew if this new disease in cows was actually transmissible to humans," she says.

In 1996, Lasmezas published a study strongly suggesting that it was. "So that was my first great research discovery," she says.

In 2005, Lasmezas came to Scripps Florida, where she continued to study the toxic particles responsible for mad cow and its human equivalent.

"These aggregated proteins are not only transmissible from cell to cell in prion diseases, they are also transmissible cell to cell in Alzheimer's disease, in Parkinson's disease, in ALS."

- Corinne Lasmezas, neuroscientist, Scripps Florida

Prions, it turns out, become toxic to brain cells when folded into an abnormal shape. "This misfolded protein basically kills the neurons," Lasmezas says.

Neurons, like other cells, depend on proteins to carry out essential tasks, like defending against germs and regulating metabolism. But to function correctly, a protein must be folded into exactly the right shape. If it folds into the wrong shape, it can kill a cell.

As scientists learned more about prion diseases like mad cow, they began to realize that misfolded proteins had a role in several human brain diseases. "Little by little," Lasmezas says, "it became clear that there are a lot of common features between prion diseases and the other diseases like Alzheimer's, Parkinson's, amyotrophic lateral sclerosis."

Cows in England suspected of having mad cow disease in 1996. The illness was traced to particular proteins that gummed up brain tissue because they didn't fold properly.

In Alzheimer's, proteins called beta-amyloid and tau misfold and form clumps. That leads to the distinctive plaques and tangles that build up in a patient's brain. In Parkinson's and ALS, different proteins misfold and aggregate.

In prion diseases like mad cow, the misfolded proteins spread by somehow causing normal, adjacent proteins to change shape. So a few years ago, researchers looked to see whether the abnormal proteins spread from neuron to neuron the same way in other brain diseases.

The evidence was clear, Lasmezas says. "These aggregated proteins are not only transmissible from cell to cell in prion diseases, they are also transmissible cell to cell in Alzheimer's disease, in Parkinson's disease, in ALS."

"What we found is ... if you replenish NAD in these neurons, it completely protects them against the injury caused by misfolded prion proteins."

When these misfolded proteins reach a critical mass, they appear to start a chain reaction that eventually destroys the brain. So Lasmezas and many other researchers are looking for ways to slow or halt that chain reaction.

One approach is to find drugs that can neutralize misfolded proteins before they spread. Another is to protect brain cells from the damage usually caused by a misfolded protein. Lasmezas and her colleague Minghai Zhou are part of a team that describe a way to do this in the current issue of the journal Brain.

The experiment involved a prion protein that kills neurons by depleting their supply of a molecule called NAD.

"What we found is that if you replenish NAD in these neurons, it completely protects them against the injury caused by misfolded prion protein," Lasmezas says.

That suggests the right drugs could protect brain cells from the misfolded proteins involved in Alzheimer's and Parkinson's and ALS, Lasmezas says.

But protecting cells is an approach designed to slow down brain diseases, not stop them. To stop the problem, she says, researchers will have to figure out precisely how normal proteins become corrupted. "We need to understand how they change their shape. What makes them misfold? What happens to them?"

The research on misfolded proteins is changing how scientists view diseases like Alzheimer's and Parkinson's, says Margaret Sutherland, a program director at the National Institute of Neurological Disorders and Stroke, which funds Lasmezas' research. "It's opened up a different mechanism for understanding the pathology behind neurodegenerative diseases," she says.

But there's still no way of knowing, she adds, whether this new understanding will lead to new treatments for these diseases.

http://www.npr.org/blogs/health/2015/03/09/390980364/mad-cow-research-hints-at-ways-to-halt-alzheimers-parkinsons

New findings on 'key players' in brain inflammation

Last updated: Wednesday 11 March 2015 at 12am PST

Inflammatory processes occur in the brain in conjunction with stroke and neurological diseases such as Alzheimer's and Parkinson's disease. Researchers from Lund University and Karolinska Institutet in Sweden, in close cooperation with a group led by Professor José L. Venero at the University of Seville, have presented new findings about some of the 'key players' in inflammation. In the long term, these findings could lead to new treatments.

One of these key players is a receptor called TLR4. The receptor plays such an important role in the body's innate immune system that the researchers who discovered it were awarded the 2011 Nobel Prize in Physiology or Medicine. The other key player is a protein called galectin-3, which is absent in healthy brains but present in a brain suffering ongoing inflammation.

"We have demonstrated that galectin-3 is secreted by microglial cells, a type of immune cell in the brain. The protein binds to the TLR4 receptor and amplifies the reactions that lead to inflammation. More galectin-3 is produced and binds to the immune cells, and the immune response is further intensified in a self-sustaining process", explained Tomas Deierborg, associate professor at Lund University.

The researchers have demonstrated the importance of the link between the two 'key players' using various different methods and in laboratory tests, animal experiments and human trials. They have shown that mice genetically modified to be incapable of synthesising galectin-3 show a lower inflammatory response and less brain damage after a heart attack. Mice with a model of Parkinson's disease also suffer less brain damage if they do not have the gene for galectin-3.

The researchers have also observed the interaction between galectin-3 and TLR4 in the brains of people who died of a stroke.

"We believe that this link could be part of the explanation for the residual disability that stroke patients often experience. High levels of galectin-3 remain in the brains of these patients long after the stroke, which may explain why the inflammatory response continues to cause damage and does not subside", said Miguel Angel Burguillos, currently working at Queen Mary University of London.

Galectin-3 is already a target for pharmaceutical companies trying to develop agents that hinder the harmful effects of the protein in neuroinflammatory diseases. The new findings on the effects and role of the protein in a diseased or damaged brain should provide important input to this work.

"Previously, it was acknowledged that galectin-3 contributed to the inflammatory response but the mechanism wasn't clear. The protein is not present in a healthy brain, only in one that is suffering an inflammatory response. Now that we understand the mechanism, this will make it easier to develop more effective treatments", said Dr Deierborg.

Adapted by MNT from original media release

http://www.medicalnewstoday.com/releases/290561.php?tw