Empathy Training
https://youtu.be/XDUxh7NM1bI
Thank you to the World Parkinson Coalition® for offering a Roundtable on empathy at the 4th World Parkinson Coalition 2016.
https://www.youtube.com/watch?v=XDUxh7NM1bI&feature=youtu.be
Saturday, October 7, 2017
New Insights on PINK1 Could Prevent Parkinson's Disease
by Rishika Gupta October 7, 2017
Source: Eurekalert
Highlights
- New insights on Structure of PINK1, a key brain protection gene could prevent Parkinson's disease
- PINK1 encodes an enzyme known as a kinase that plays a critical role in protecting brain cells against stress.
- In PINK1 mutations bearing patients, this protective effect is lost leading to the degeneration of cells.
New insights on PINK1, a key brain protection gene could prevent Parkinson's disease, found a new study published in eLife journal
The result of a decade of work, the research team said that solving the 3D structure and inner workings of the PINK1 enzyme represented a major breakthrough.
‘PINK1 encodes a special class of enzyme known as a kinase that plays a critical role in protecting brain cells against stress. ’
"Solving the structure and workings of PINK1 gives us crucial insights in to how it exerts a protective role in Parkinson's," said Dr Miratul Muqit, Wellcome Trust Senior Clinical Fellow and Consultant Neurologist at the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU) in the School of Life Sciences, who co-led the research team with Professor Daan van Aalten at the University.
"That knowledge can lead to the development of new drugs which could be designed to 'switch on' PINK1 to the benefit of patients with Parkinson's." Professor van Aalten, a Wellcome Trust Investigator in the Division of Gene Regulation and Expression in the School of Life Sciences, said, "There has been great interest in directly targeting PINK1 as a potential therapy, but without knowledge of the structure of the enzyme, this posed a major barrier.
Our work now provides a framework to undertake future studies directed at finding a new drug-like molecules that can target and activate PINK1."
Parkinson's is a progressive degenerative brain disorder which to date remains incurable. Previous advances in genetics identified mutations in the PINK1 gene in patients with early-onset forms of Parkinson's.
PINK1 encodes a special class of enzyme known as a kinase that plays a critical role in protecting brain cells against stress.
In patients harboring PINK1 mutations, this protective effect is lost leading to the degeneration of cells controlling movement that account for Parkinson's symptoms.
Previous work had indicated that the main role of the PINK1 enzyme is to sense damage to the energy centers of cells known as mitochondria and then switch on a protective pathway involving the targeting of two key proteins, ubiquitin, and Parkin, to reduce the damage. But how this occurred was unknown.
In the new research, published in the journal eLife, the team of Dundee scientists reveals that PINK1 has unique control elements not found in other enzymes of this class that explain how it targets ubiquitin and Parkin to exert its protective role in Parkinson's.
"This provides detailed insights into how mutations carried by hundreds of Parkinson's patients worldwide interrupt the function of the enzyme," said Professor van Aalten.
"This is a good example of collaborative research resulting from scientists with different expertise working together. It is only with the hard work of several Ph.D. students and postdocs that we have been able to make this transformative step in our understanding of how PINK1 works. As is often the case, has now solved this important problem, there are many new interesting questions on PINK1 that will direct our future research."
Dr. Muqit added, "Our research has been focused on defining the most fundamental aspects of the causes of Parkinson's which we think will uncover new ideas for better treating the disease in the future."
Michael Dunn, Head of Wellcome's Genetics and Molecular Sciences team, said, "The PINK1 protein has been the focus of research all over the world, so this finding from the Dundee team is a fantastic step forward for the community. If we understand the structure of this protein, which holds so many clues into what goes wrong in Parkinson's, it may help us develop novel drugs to protect against this devastating disease. Basic research is fundamental to understanding and treating many diseases and only by working in collaboration can we hope to make breakthroughs like this."
Dr. Nathan Richardson, MRC Head of Molecular and Cellular Medicine, said, "Discovering the fundamental structure of this protein is vital for understanding its cellular function and paves the way for the development of drugs to combat forms of early-onset Parkinson's disease. This advance will also help reveal the molecular basis of genetic mutations in Parkinson's disease, illustrating the merit of long-term support for underpinning biomedical research."
Professor David Dexter, Deputy Director of Research at Parkinson's UK, said, "The PINK1 gene was identified as a key player by Parkinson's UK-funded researchers back in 2004.
Drugs that can switch the PINK1/parkin pathway back on may be able to slow, stop or even reverse nerve cell death, not only in people who have these rare inherited forms of the condition, but also those with non-inherited Parkinson's.
"This research, for the first time, gives us a view of what the PINK1 protein looks like and how changes in the gene can prevent the PINK1 protein working properly. This knowledge is vital for developing drugs that can switch PINK1 back on, which has the potential to slow or even stop the progression of the condition, something current treatments are unable to do."
Source: Eurekalert
http://www.medindia.net/news/healthwatch/new-insights-on-pink1-could-prevent-parkinsons-disease-173583-1.htm
Living with Parkinson’s
October 7, 2017 Rachael Smith
Support, exercise key to battling progressive nervous system disorder
Frank Posey
Tillie Winfield puts socks and shoes on her husband George every morning. She handles most of the everyday household tasks, even those that involve tools like a screwdriver or a hammer.
“You don’t realize what you can’t do until you’re there,” she said. “He handles it better than I do; he’s never angry, he’s always very calm. It could make you angry at life, but he doesn’t show that at all. He’s better and more capable at doing everyday life than I am. He’s really a great guy.”
George Winfield, 79, was diagnosed with Parkinson’s disease in 2007 after he complained about being tired, not having enough energy and feeling pain in different areas of his body.
Parkinson’s is a chronic and progressive movement disorder that affects the nervous system. The symptoms continue and worsen over time. According to the Parkinson’s Disease Foundation, there are 1 million people in the United States living with it.
Symptoms vary greatly but predominantly include tremors, trouble with balance, stiff muscles and difficulty walking. It can eventually lead to dementia.
Though George Winfield didn’t have the telltale sign of tremors at the time of his diagnosis, he began having them five years ago. “He’s worse now,” Tillie Winfield, 78, said. “He has a hard time doing anything using his fingers. It’s very difficult.”
Tillie Winfield said the disease’s slow progression gradually has robbed her husband of his ability to complete everyday tasks. Some mornings, he needs help getting dressed.
“It’s not just about getting old,” she said. “The tremors get worse and that causes a lot of problems.”
George Winfield formerly worked as a manager of Sears department stores and the couple lived in Arkansas, Tennessee, Alabama and North Carolina before settling in Virginia.
“He was always so strong and very active as far as doing anything,” Tillie Winfield said. “He always did the heavy lifting and he can no longer do that.”
In September, the couple moved from a five-bedroom, three-bath home on 23 acres in Amherst County, where they lived since 1994, to a more manageable three-bedroom home in Madison Heights.
Tillie Winfield said the couple’s former home had a garden and several fields that George Winfield would mow himself.
She said they enjoyed having so much space to themselves.
“We had to get rid of a lot of stuff, that was the hardest part,” she said.
Some of those items included photos and other personal belongings that they gave to their four children.
“We were not able to take care of things anymore because of his disease,” she said. “It had gotten to the point that we were not able to do as much.”
Though the relationship has changed, she and her husband still love each other dearly.
“We have other things to deal with and we just deal with it. You don’t have a choice,” she said.
She said the disease taught her to learn how to deal with the cards life has handed her.
“You have no choice but to deal with whatever God gives you,” she said. “So that’s what we do. What else can we do?”
A local support group helps them deal with the challenges together.
**
The Lynchburg Parkinson’s Support Group meets every third Tuesday at 2 p.m. at The Summit in Wyndhurst. What began in 1986 with about 15 caregivers and patients has grown to a mailing list of 70.
The group offers a space for patients and caregivers to interact, talk about their situation and get updates on the latest Parkinson’s research. Speakers have included physicians, therapists, pharmacists, psychologists, religious leaders and other experts who can shed some light on ways to cope with Parkinson’s and its symptoms.
George Winfield’s doctor advised him to avoid the group when he was diagnosed.
“He thought that by going in the early stages that he would see people who were in the last stages and it would affect him,” Tillie Winfield said. That never happened and the couple continues to go, learn new things and make new friends.
“The support group is wonderful,” Tillie Winfield said. “We have learned how to deal with certain things. Difficulties are every day and the discussion groups help us find out how other people take care of certain things.”
For example, she said, the group helped her husband learn how to better cut his meat and hold his utensils. Something as simple as grasping a spoon has become increasingly difficult.
Wendy Posey, 63, leads the group. Her husband of 37 years, Frank, was diagnosed with Parkinson’s in 2002.
She was an office manager for a doctor in Pennsylvania when the doctor noticed changes in Frank Posey’s balance.
“The neurologist made it sound like it was no big deal,” she said. “It wasn’t until my friend told me I wasn’t taking it seriously. She bought me a book to read and said, ‘You need to be on top of this’ and I’m so grateful to her.’”
Frank Posey worked in computer sales management for 30 years. He retired four times from different computer sales jobs and once from teaching higher levels of math to a home school group in Lynchburg, where he taught for eight years.
He even served as a Boy Scout usher at Dwight Eisenhower’s inauguration.
Fifteen years after the neurologist visit Frank Posey displays some of the most common symptoms including tremors and trouble with speech and balance. Sometimes he freezes and can’t move, feeling paralyzed.
According to the National Parkinson Foundation, most patients’ symptoms take years to develop.
There is currently no cure, but there are many medications to help maintain quality of life. The average onset age for the disease is 60 years old; it strikes 50 percent more men than women.
“You’re not going to get better from it,” said Posey, who is upbeat, chatty and extremely positive despite the diagnosis. “Parkinson’s isn’t going to kill him, but one of the results from it will.”
After he suffered from a stroke in February last year, Wendy Posey gave her husband a choice.
“I’m not going to make you fight this disease if you don’t want to, but if you want to fight, buddy you’re going to work,” she told him.
And work he does at the Jamerson YMCA three days a week with a personal trainer. While Wendy Posey sits in the lobby reading a book, Frank Posey, 76, uses his walker and walking sticks to move between each station at the gym.
When he’s not training he’s riding a stationary bike or lifting weights.
“Before I got Parkinson’s, Wendy and I did a lot of hiking and biking and biking was the last thing to go,” he said. “I was looking for something else to do.”Speaking softly, as he now does because the disease has weakened his vocal chords, Frank said the good days outweigh the bad. His philosophy is simple: bullies can’t win and in his mind, Parkinson’s is a bully.
“You have two choices with Parkinson’s. You can let it win or you can fight it, and I’m gonna fight this,” he said.
***
Pat White is using the YMCA and the support group to fight the disease, too.
Her husband Jimmy White, now 84, led the Lynchburg Parkinson’s Support Group for a decade before passing the torch to Posey a few months ago.
Pat, 82, was diagnosed with Parkinson’s 50 years ago. The couple has been married for 63 years.
Pat White was only in her mid 30s when diagnosed. She was frustrated when her legs began trembling and she didn’t feel up to attending her kids’ after-school extracurricular activities, like baseball games.
“That was one thing that always bothered me,” she said. “I didn’t feel like going. My nerves were so bad and it was uncomfortable.”
She said that the symptoms come and go and are unpredictable.
At one point she was able to go shopping frequently, but now only goes from time to time.
“I go when I can but most of the time I stay home,” she said.
She said just to get dressed can be exhausting.
Sometimes she has plain trembling in her legs and other times, if she takes her medicine too early before she eats, she gets dyskinesia, which is caused by certain Parkinson’s medications that cause involuntary movements.
She remembers going shopping one day and trying to cross the street but her legs wouldn’t move. She said she was frozen until her husband helped her.
“It’s embarrassing and scary,” said Pat, who even after decades with the disease worries what people think when her legs tremble. She has broken both of her shoulders and two toes as well as cracked a rib during separate falls.
“Once you start falling there’s no stopping it, you just go down,” Jimmy White said. “You’re limited in so many things that you can’t do or are afraid to do.”
He said it’s important for caregivers to make time for themselves and to go out and run errands.
“Caregiving is a tough situation sometimes. It’s a tough road. I try not to leave her at home by herself. If I go somewhere I try to have someone available to sit with her.”
The White’s encourage anyone with the disease to try out the support group because of all the good it has done their family.
“Come and be active and try to maintain a positive attitude,” Jimmy White said. “It’s a degenerative disease and unfortunately you don’t get better as time goes on but you can put off the inevitable by remaining active. Exercise is the key to the whole thing.”
***
Exercise is medicine, according to YMCA Parkinson’s Wellness Recovery Moves fitness class instructor Terry Brame.
“Exercise is very, very important for Parkinson’s,” she said, explaining that exercise helps to slow the progression of the disease.
The eight-week class at the Jamerson YMCA meets on Tuesdays and Thursdays at 1:15 p.m. About 13 people attend on a regular basis, and most of them also attend the support group.
It focuses on posture, balance, twisting and large movements.
Brame, who has been working with Parkinson’s patients for two years and has a certification to teach the class as well as a personal training and senior fitness certification, has seen improvement from patients who have joined the class.
George Winfield completed a six-week workout course last week at Lynchburg College that specializes in exercise for those with Parkinson’s.
Tillie Winfield said the class made a big difference. Even though his back is still slouched over, her husband can hold his shoulders back better.
“Exercise is really the most important thing that any Parkinson’s patient can do,” she said.
Exercising has changed Clellan Berry’s outlook on the disease and slowed her symptoms.
Berry, 69, was diagnosed 10 years ago and fell into a depression.
“I thought I wouldn’t be good to anybody,” she said. “I couldn’t even carry a bowl of water to the dogs without it splashing everywhere.”
She works out at the BWX Technologies gym in Mt. Athos, where her son is an employee.
She does planks, kettle bell lifts and walks on the treadmill. She has been a participant of the Virginia 4-Mile Walk for five years now.
She describes herself as hard-headed and determined.
“You get it before it gets you. You get a hold on it and don’t give up,” she said. “It’s not a death sentence. You can deal with it and be strong.”
http://www.newsadvance.com/news/local/living-with-parkinson-s/article_6ee3b21d-540d-5196-86c5-3106bc0dbd78.html
Higgins: Nearly $400,000 federal grant for Parkinson's disease research at University at Buffalo
October 6, 2017
 |
| Congressman Brian Higgins |
Congressman Brian Higgins announced a federal grant totaling $398,750 for clinical research focused on Parkinson's disease at the State University of New York at Buffalo. The award is provided through the National Institutes of Health Institute of Neurological Disorders and Stroke.
"Parkinson's is a difficult, progressive condition with no cure," Higgins said. "This federal investment in research conducted right here in Western New York hopes to provide new clues into the disease and how we can better treat it."
Parkinson's disease is a motor system disorder resulting from the loss of dopamine-producing cells in the brain. The new award from NINDS will support Dr. Jian Feng's continued research into how mutations in the parkin gene affect dopamine neurons in the brain, leading to Parkinson's disease.
"During the past few years, we have made a lot of progress," said Feng, Ph.D., professor in the department of physiology and biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB. "We have found a way to make human neurons in a dish that are very similar to human dopamine neurons in patients' brains. This is critical since it is the only way we can study live neurons. Using stem cell technology, we are able to make these human neurons. This has allowed us to study them directly to find out why parkin mutations cause these neurons to become more fragile. If we can find a way to mimic the protective function of parkin, then we will be able to find a therapy for Parkinson's."
Feng's research has led UB to enter into discussions with several pharmaceutical companies and to file for patent protection.
According to the National Institutes of Health, about 50,000 people in the U.S. are diagnosed with Parkinson's disease annually, and about 500,000 people have the disease.
Higgins is co-chair and founding member of the bipartisan House of Representatives National Institutes of Health Caucus, and lead sponsor of the Accelerating Biomedical Research Act, which proposes incremental increases in funding to the NIH.
https://www.wnypapers.com/news/article/current/2017/10/06/130066/higgins-nearly-400000-federal-grant-for-parkinsons-disease-research-at-university-at-buffalo
FIGHTING BACK - Rock Steady Boxing lets people with Parkinson's battle the disease
October 7, 2017 By Andy Vineberg, staff writer
Boxing class is in session at the Katz Jewish Community Center in Cherry Hill, and instructor Stacey Macaluso is fired up.
"Hands up!" she barks as her eager-to-learn trainees shadowbox their reflections in the mirrored wall. "I see a lot of you with your hands down. You're gonna get your butts kicked if your hands are down! Aim for your face! Punch your face!"
The gloved participants, the oldest of who is 82, comply, throwing jabs, crosses, hooks and uppercuts at the air, pivoting their feet when Macaluso tells them to.
If you closed your eyes and just listened to her exhortations, you'd never know that these weren't "real" boxers, that they won't be punching anybody in this class or anywhere else.
They are, however, fighting back.
The class is Rock Steady Boxing, a national nonprofit organization founded in 2006 in Indianapolis that offers people with Parkinson's disease the chance to stand up to their symptoms through rigorous, noncontact fitness training that includes heavy bags, speed bags and other boxing-related exercises.
"My friends think, yeah, right, Dianne boxing," Dianne Fisher, of Mount Laurel, who was diagnosed seven years ago, said after the hour-long session. "Then I explain what it does for me. I feel really good now, I feel like I could do what I was typically doing before I was diagnosed. But it doesn't last for a long time. You've got to keep doing it, you've got to come back."
Fisher and Lori Katz, of Cherry Hill, have been participating in the program for four years in Philadelphia, and both are happy that it's now available in South Jersey. The JCC is currently offering four different eight-week classes of eight people each, although 29 of the 32 spots are filled.
"Rock Steady Boxing is what's called forced exercise, which means you're pushed to do almost more than you can do," said Katz, who was diagnosed in 2005. "The more forced exercises you do, the better the outcome of the Parkinson's, rather than sitting in one place not doing anything."
The program also is offered at Unbound Synergy in New Hope, with four different sessions during the week.
"They're real fighters," Anne Haneman, who co-coaches the program in New Hope with Joanne Haug, said of the participants. "We're in this together with them to help fight the disease process. Joanne and I are both physical therapists, we've been educated in all the physical therapy treatments for people with Parkinson's, and we feel this is by far the most beneficial."
Back in Cherry Hill, Maculuso would absolutely agree. Her fervent, nonstop energy is contagious as she rouses the participants through warm-ups, group exercises and individual drills, shouting over the uplifting rock 'n' roll music she has playing in the room.
"Do you want to talk to me or punch me?" she asks 82-year-old Norbie Fuchs, of Evesham, as he approaches her during a break. "I know, it's hard to decide."
Fuchs, who was diagnosed nine years ago, is one of the few people in this class with real boxing experience, having competed in the Police Athletic League in the Bronx in 1949. And while he doesn't see many similarities to those days ("the gloves are different, the tape is different, it's all different"), he absolutely loves this program, in large part because of Macaluso, who worked with him at the Rohrer Center in Voorhees.
"I really felt like I couldn't do anything until I got this maniac," he said. "She's a dynamite lady, a tough lady. That's what you need."
Macaluso and fellow JCC instructor Melanie Montana were trained in Indianapolis, where they received the required certification to run the program. Their trip was largely financed by Parkinson's patient Kevin Murray, whose wife, Susan, started the Livin' La Levodopa foundation in 2002 to raise money and awareness. Murray, 59, of Berlin, is also a participant in the program.
"Exercise is very important for people with Parkinson's," said Murray, who was 41 when he was diagnosed. "I tried different exercises — water aerobics, Zumba, all that stuff, but I found this is the exercise I enjoy. My balance is better, my range of motion. And it doesn't hurt to sweat a little and punch the bag."
Punching the bag is just one of the individual activities available to the participants, who are accompanied by spouses or other volunteers — their "corner men" (or women). Some stations are harder or more physically taxing than others, but nobody seems reluctant to move to the next one. At one of the stations, they get to don gloves and punch at Macaluso, wearing sparring mitts, who encourages them to come at her harder.
"You notice how everybody's smiling," Murray said during the session.
Before the program begins, participants go through an orientation and their skills are tested so they can be placed with people with similar levels of the disease, JCC assistant fitness director Jayne Miller-Morgan said. This particular class features veterans of the program but also a newcomer in Carmel Dorsey, of Moorestown.
"I'm really hoping to, not eliminate, but downplay my symptoms," she said. "I'm not a physical person by any stretch. It's a little bit harder for me because I was totally uncoordinated when I was well. To do this kind of stuff is a little bit on the other side of what I thought I'd do, but I'm willing to try anything. My kids think it's awesome."
Macaluso marvels at the way the participants have responded, and also at the physical improvements she's seen. Just two weeks ago, she said, Fuchs had a lot of trouble getting his feet over a heavy bag, one of the exercises during the individual activities. On this day, she noticed how high he was able to lift his legs.
"His wife was astounded he was able to do that," she said.
The session ended with a group huddle and a rallying cry led by Macaluso to "Show Parkinson's what we can do, we're going to kick the (heck) out of you. Who are we, we're Rock Steady!"
Macaluso was still buzzing as she talked about the program after the last of the participants had left the room. She was introduced to the Parkinson's community through dance therapy and has taught that for five years, but this takes the fight against the disease to another level.
"I love my dance for Parkinson's disease class, but that's a little bit more of a gentle format, so people come in with a little more gentle mind," she said. "When people come to this Rock Steady Boxing class, they're ready to fight back, ready to kick Parkinson's in the butt and stop the progression, reduce the symptoms and see the improvements that can be done by forced intense exercises.
"That's the whole idea, really — working with your students to push them a little further than they would go on their own. What they've found is that forced intense exercise really makes a difference."
http://www.theintell.com/life-style/local-feature/rock-steady-boxing-lets-people-with-parkinson-s-battle-the/article_52885841-467b-5b32-a20f-26015bf7a9b1.html
"Ali" author on painting a "real" picture of the legendary boxer
OCTOBER 7, 2017
Cassius Clay exploded onto the scene in 1960 as the audacious boxer known as the Louisville Lip. Clay would soon become Muhammad Ali and change the course of American history first as a heavyweight champion and in later years as a civil rights activist, anti-war crusader, and a beloved figure who valiantly fought Parkinson's disease. Jonathan Eig discusses his epic new biography, "Ali: A Life." Anthony Mason reports.
https://www.cbsnews.com/videos/ali-author-on-painting-a-real-picture-of-the-legendary-boxer/
Friday, October 6, 2017
Hospital Refuses Care to Man With Parkinson’s Who Broke His Hip, Until Someone Stepped In
NATIONAL KATIE SHORT OCT 6, 2017 | WASHINGTON, DC
Life Legal regularly receives calls from family members of patients who are mistreated or denied care in hospitals around the country. These are often extraordinarily difficult cases that require immediate, life-saving action.Over the weekend, one of my family members required Life Legal’s intervention.
On Saturday evening, I visited my sister’s father-in-law Leon in the hospital. He suffers from Parkinson’s disease and had broken his hip in a recent fall. I saw him in the hospital two days after his hip replacement surgery.
When I entered his room, I was appalled. This was not the same man I had seen at a family gathering just two weeks prior. His skin was yellow, he was gasping for air, and he was obviously in distress. I asked the family what was going on and they said the nurses told them his behavior was “normal.”
But I knew something was terribly wrong.
I went to the nurses station and got the brush off. “We’re watching him,” they said. But in the thirty minutes I had been there, no one looked in on him despite the family’s repeated pleas for help.
When I checked on Leon again, he looked even worse. His breathing was shallow and his eyes were rolling back in his head.
I decided it was time to pull out the attorney card. I asked for help again, saying the patient was my sister’s father-in-law and that I am an attorney with experience in cases like this.
Within minutes, a barrage of nurses and techs rushed into Leon’s room. He was immediately hooked up to an oxygen mask, received a chest X-ray, and was on his way to another floor where he would be carefully monitored. Shorty afterward, his cardiologist and neurologist arrived for a thorough evaluation. This, despite the fact that the family had been begging the nurses to call his doctors for two days.
Clearly this hospital offered excellent care. But the family was unable to access that care on behalf of their loved one, in part because he was confused and unable to speak for himself.
What should have been a fairly routine recovery nearly ended in tragedy.
Patients and their advocates should not have to threaten legal action to get adequate care in a medical facility that is fully equipped to provide such care.
Please join Life Legal as we go to bat for patients who do not receive the life-saving medical care they need. We rely completely on your help to save the lives of people like Leon and others who cannot advocate for themselves.
Please pray for Leon’s full recovery!
http://www.lifenews.com/2017/10/06/hospital-refuses-care-to-man-with-parkinsons-who-broke-his-hip-until-someone-stepped-in/
Researchers Studying Drug’s Potential to Prevent Alzheimer’s
NEUROSCIENCE NEWS OCTOBER 6, 2017
Summary: Researchers are testing whether low doses of Rapamycin, a drug most commonly used as an immunosuppressant following an organ transplant, can help to prevent Alzheimer’s disease.
Source: University of Kentucky.
Lin will be studying the drug in mice with the APOE4 gene, which is associated with an increased risk of AD. She will validate mMRI results with biological and behavioral tests to confirm mMRI’s accuracy. NeuroscienceNews.com image is in the public domain.
Researchers have known for decades that the hallmark plaques and tangles in the brain associated with Alzheimer’s develop long before people experience memory loss. Ai-Ling Lin, an assistant professor at Sanders-Brown, hopes to demonstrate that low doses of Rapamycin, a drug commonly used as an immunosuppressant for organ transplant recipients, can restore brain function before the disease changes in the brain affect a person’s memory.
“We know that Rapamycin signals blood vessels to dilate, which increases cerebral blood flow and helps regulate the physical and chemical processes that support effective cell function – also known as metabolic homeostasis,” Lin said. “We hope our research will demonstrate that Rapamycin prompts tangible benefit by preventing the cognitive decline associated with Alzheimer’s disease.”
Her study is unique in that it will also assess whether a relatively new imaging concept called multimodal MRI (mMRI) is effective in measuring the efficacy of other potential treatments. mMRI uses traditional MRI plus another form of imaging (CT scan or PET scan, for example) to provide complementary information.
“We have two eyes for a reason. You can function with just one, but eyesight is improved when both eyes work well,” Lin explained. “mMRI follows the same concept: multiple layers of data increase accuracy.”
“If I can demonstrate that mMRI is an effective surrogate for the types of testing we currently have at our disposal, we have a new avenue to explore potential treatments on a faster and more straightforward track.”
Lin will be studying the drug in mice with the APOE4 gene, which is associated with an increased risk of AD. She will validate mMRI results with biological and behavioral tests to confirm mMRI’s accuracy.
Her work will be funded by a five-year, $2.88 million grant from the National Institutes of Health.
It will be a while before Rapamycin as a therapeutic target for Alzheimer’s will be ready for human clinical trials, but the concept of mMRI as a surrogate for other testing methods has potential for speedy adoption, as the mMRI methods are readily available to be used in humans. “Being able to test a drug and also a means of assessing other drugs in the future is truly exciting,” Lin said.
Linda Van Eldik, director of the Sanders-Brown Center on Aging, says that this latest grant is another important step in Sanders-Brown’s race against Alzheimer’s.
Her work will be funded by a five-year, $2.88 million grant from the National Institutes of Health.
It will be a while before Rapamycin as a therapeutic target for Alzheimer’s will be ready for human clinical trials, but the concept of mMRI as a surrogate for other testing methods has potential for speedy adoption, as the mMRI methods are readily available to be used in humans. “Being able to test a drug and also a means of assessing other drugs in the future is truly exciting,” Lin said.
Linda Van Eldik, director of the Sanders-Brown Center on Aging, says that this latest grant is another important step in Sanders-Brown’s race against Alzheimer’s.
“As many as one in five people carry the Alzheimer’s gene APOE4, so the idea that a readily-available drug already demonstrated to be safe in humans might prevent what is arguably the most devastating and expensive disease in modern history is exciting,” said Van Eldik. “On top of that, Ai-Ling’s work might also speed the ability to test other treatments. It’s a win-win for science and for the people it serves.”
Source: Laura Dawahare – University of Kentucky
Image Source: NeuroscienceNews.com image is in the public domain.
Image Source: NeuroscienceNews.com image is in the public domain.
Video Source:NeuroscienceNews. Retrieved October 6, 2017 from http://neurosciencenews.com/alzheimers-prevention-drug-7676/[/cbtab]cbcut
http://neurosciencenews.com/alzheimers-prevention-drug-7676/
Personalizing Stem Cell Therapy for Parkinson’s Disease
October 6, 2017
Kwang-Soo Kim, PhD
In the United States alone, as many as one million people have Parkinson’s disease (PD), with approximately 60,000 cases being diagnosed each year, according to the Parkinson’s Disease Foundation. Kwang-Soo Kim, PhD, director of the Molecular Neurobiology Laboratory at McLean Hospital and professor of psychiatry at Harvard Medical School, is committed to finding a way to lower those numbers.
Kim’s team is at the forefront of investigating personalized, stem cell-based therapy for PD. He has developed a novel, highly efficient, and safe way to reprogram patients’ own cells to become functioning midbrain dopamine cells—the cells whose loss primarily causes the disease. These cells, which produce the neurotransmitter dopamine, occupy a specific area in the brain’s substantia nigra and project into the dorsal striatum, forming the so-called nigrastriatal pathway. This is the major neuronal pathway controlling human movement, with its disruption leading to the tremors, stiffness, gait changes, and difficulty initiating movements that characterize PD.
Kim’s method overcomes the limitations of other stem cell therapies for PD. It uses patients’ own cells, derived from their skin and transformed into induced pluripotent stem (iPS) cells—cells that behave like embryonic stem cells in that they can develop into practically any cell type. The strategy eliminates not just the possibility of immune rejection but also the ethical issues tied to embryonic stem cell research. It relies on non-viral, footprint-free methods to reprogram the skin cells (such as protein-based or plasmid-based methods) rather than the standard viral delivery system that carries the risk of disrupting patients’ chromosomal DNA and canceling out tumor suppressor genes or activating cancer-causing ones.
Finally, his method removes any remaining “undifferentiated” cells—those that have not yet become a specific cell type—before transplantation, thereby prohibiting tumor formation. Kim’s group added this important step when they discovered that several small molecules, including the natural compound quercetin, selectively kill undifferentiated stem cells. They do so by targeting the survivin gene (BIRC5), which is specifically abundant in undifferentiated cells.
“In terms of cell therapy, the most important criterion is safety,” said Kim. “We now have a very robust, optimized protocol for iPS cell-based autologous cell therapy. Many studies have shown that tumor formation after transplantation is directly proportional to the amount of remaining undifferentiated cells. Our method removes them completely. And by using a non-viral method to reprogram the iPS cells, we can maintain the cells’ genetic integrity.”
The Role of Dopamine in Parkinson’s Disease
Kim has been studying the molecular biology of dopamine neuronal systems for more than 25 years, 18 of them at McLean. His research at the hospital concentrates on the development and maintenance of the neurons themselves. “What makes a dopamine neuron become a dopamine neuron?” he said, describing it as the burning question he wanted to address. “What goes wrong with dopamine neurons in the case of disease?”
Turning to stem cell research to answer these questions was a natural progression. Stem cells are essentially a tabula rasa: they can give rise, through the process of differentiation, to any kind of specialized cell, for example, a heart, liver, or muscle cell, depending on how the stem cell’s genes interact with the physical and chemical conditions in its environment.
Kim set out to find what would turn stem cells into the specific dopamine cells degenerating in PD—midbrain dopamine (mDA) neurons in the substantia nigra. He initially used mouse embryonic stem cells to generate mDA neurons and transplanted them into the brains of mice or rats engineered to have traits of PD.
“We could see that this transplantation had the potential to rescue the motor function defect in the animals,” said Kim. “But at the same time, there were some very significant limitations in that some of the animals developed tumors, and differentiation to mDA cells was not very efficient.” In 2009, he shifted his attention to human iPS cells generated from human skin cells. Using a direct protein method to deliver the genes that would trigger the transformation eliminated the risk of disrupting the cells’ chromosomal DNA, but the process was slow, and the produced iPS cells varied in their ability to differentiate into mDA neurons.
Recently, Kim and his colleagues discovered a fundamental mechanism underlying the change in metabolic properties that accompanies the skin cells’ reprogramming. The finding enabled them to develop a novel reprogramming method, for which they are awaiting a patent.
“Based on our new method, we can make iPS cells with much greater efficiency, and they show much less variation,” Kim said. “They are almost standardized in their ability to differentiate into mDA neurons.”
Optimizing the Differentiation Protocol
Differentiating iPS cells into particular cell types is tricky, but Kim’s lab has gone a long way toward doing so, spending countless hours bent over petri dishes investigating which signals transform them into functional mDA neurons. One of these differentiation technologies was recently licensed to the stem cell company Cellular Dynamics, based in Madison, Wisconsin, and the protocol itself is patent pending.
“My lab is continuing to optimize the differentiation protocol, because if you think about brain development, there are maybe tens or even hundreds of different signals taking place in a temporal-specific manner, in a gradient-specific manner, in a combinatorial manner to drive specific neuronal lineages,” said Kim. “We now have an effective protocol that can make large proportions of mDA neurons.”
“My hope is that in the not too distant future we will be ready to run a human clinical trial.”– Kwang-Soo, Kim, PhD
The current challenge is to test the human mDA neurons in an animal model to determine the best stage at which to transplant them and how many to transplant to reverse Parkinson’s effects. For that, Kim and his colleagues are using the popular 6-OHDA lesion rat model. The researchers inject the chemical 6-OHDA, which kills dopamine neurons, into one side of the nigrastriatal pathway, causing a lesion and stopping dopamine function. Behaviorally, upon administration of apomorphine, the rat will rotate to the lesion side, as movements will now be driven by the intact side. They then inject the new mDA neurons into the lesion side, wait three to four months for the transplant to “take” and new neurons to grow, and make careful computer-generated measurements of the rat’s rotation recovery. Later they sacrifice the animals to analyze the extent of the neuronal growth in their brains and how that growth relates to the elimination of symptoms.
“With all this analysis, we can come up with the most accurate calculations for real transplant conditions,” said Kim. “My hope is that in the not too distant future we will be ready to run a human clinical trial.”
http://www.mcleanhospital.org/news/2017/10/06/personalizing-stem-cell-therapy-parkinsons-disease