Effect of L-Dihydoxyphenylserine on Locomotion, Postural Stability, and Fall Risk Reduction in Parkinson Disease

June 27, 2016

Summary

This research study is being done to determine whether treatment with L- Dihydroxyphenylserine (L-DOPS) versus placebo (an inactive substance that looks like study drug) in addition to other Parkinson Disease (PD) drugs will improve balance, walking, and reduce risk of falls and/or severity of falls in PD subjects. The study is also being done to determine the effectiveness, safety, and tolerability of L-DOPS, and whether it will decrease Freezing of Gait (FOG), improve apathy (generalized disinterest) or show a relationship between apathy and slowed movement and fall risk.

Description

Among the top three priorities presented to the National Institute of Neurological Disorders and Stroke (NINDS) Council 22 as final recommendations of critical needs for advancing Parkinson Disease (PD) research in 2014 is to develop effective treatments for dopa-resistant features of PD. These features include symptoms such as gait and balance problems, and freezing of gait leading to falls. In order for these goals to be realized, dysfunctional motor patterns in patients with gait and balance problems need to be accurately defined and assessed using body-fixed sensors and other newer computation technology to enhance sensitivity and specificity of measurement to facilitate long-term follow-up. The proposed research will meet the challenge of determining appropriate intervention (L-DOPS) for dopa-resistant features of PD in improving gait and posture using innovative quantitative analyses derived from body-worn sensors. Injuries associated with fall incidences continue to pose a significant burden to persons with Parkinson's disease (PD) both in terms of human suffering and economic losses. Annual fall incidence rates range from 50-70% of patients with PD. Recurrent falls especially, are a major cause of disability in PD. 

The resulting loss of independence and treatment costs add substantially to the healthcare expenditures in PD which was estimated to be $27 billion annually2. This number may rise substantially in the coming decades as the entire US population ages. Any intervention that is cost effective at reducing fall risk could have important benefits for patients and families, and for the entire healthcare system. In this study, we will determine whether treatment with L- Dihydroxyphenylserine (L-DOPS, Northera) in addition to dopaminergic drugs will improve postural stability and activity of daily living, and reduce fall risk and/or severity of falls in PD patients.Falls, early in PD (within 5 years of diagnosis) probably arise from slowed locomotion. Slowed locomotion is corrected by dopaminergic drugs, hence falls early in PD are decreased by such drugs. Later in PD (5 or years after diagnosis) falls, recurrent falls, occur despite such drugs. There is evidence that falls late in PD occur because of impaired postural stability which does not respond to dopaminergic drugs or may be made worse by such drugs. 

A single fall, although serious, may be only partly related or even unrelated to PD. "Serious fall" is defined as: all four limbs hit the ground, the skull hits the ground, or there is soft tissue or bone injury. However, some people with PD fall repeatedly. In such patients the role of impaired postural stability was stressed. Although the mechanisms underlying impaired postural stability are not well-known in patients with PD, attention is focused on the noradrenergic system. L-DOPS, a drug that enhances norepinephrine levels in the peripheral and central nervous systems, has been shown to moderate orthostatic hypotension, and often improve some PD symptoms. 

There is evidence that mechanisms related to norepinephrine centers in the basal forebrain and the locus ceruleus play a role in maintaining postural stability in activities of daily living. They may play a role in preventing or ameliorating falls and freezing of gait. FOG is a major problem in patients with PD who fall. There is evidence that L-DOPS, by improving FOG, decreases risk of falls. Additionally, evidence indicates that L-DOPS decreases falls independent of improving FOG. 

Apathy, a major and disabling non-motor symptom of PD, may be related to decreased central norepinephrine levels. Apathy may be associated with slowed movements and slowed movements may contribute to falls. There is evidence that L-DOPS, by increasing central norepinephrine, may improve apathy and this may result in a decreased risk of falls.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Conditions

Parkinson Disease

Intervention

L-DOPS, Placebo

Location

Barrow Neurological Institute/St. Joseph's Hospital and Medical Center

Phoenix

Arizona

United States

85013

Status

Recruiting

http://www.bioportfolio.com/resources/trial/160761/Effect-of-L-Dihydoxyphenylserine-on-Locomotion-Postural-Stability-and-Fall-Risk-Reduction.html

Donated Blood Won't Transmit Alzheimer's, Parkinson's Disease

June 27, 2016

Swedish study of nearly 1.5 million patients finds no increased risk when blood came from affected people

People who've received a blood transfusion can breathe a bit easier: A new study finds no evidence that degenerative brain disorders can be transmitted via donated blood.

"This study provides reassurance to individuals who have received blood transfusions from patients with Alzheimer's or Parkinson's disease," said Dr. Irving Gomolin, a geriatrician who reviewed the Swedish study findings.

"It demonstrates that the transmission of these diseases via blood either is not biologically possible or, at worst, must be exceedingly rare," said Gomolin. He is chief of geriatric medicine at Winthrop-University Hospital in Mineola, N.Y.

In the study, a team led by Dr. Gustaf Edgren, of the Karolinska Institute in Stockholm, tracked data on more than 40,000 patients in Denmark and Sweden. All of the patients had received blood transfusions between 1968 and 2012 from people who were later diagnosed with any form of dementia or Parkinson's disease.

These patients were compared with over 1.4 million patients who did not receive blood from donors later diagnosed with these illnesses.

Patients in both groups had exactly the same chance of developing a neurodegenerative disorder, which clearly shows that these diseases cannot be transmitted through blood transfusion, the researchers said.

The study, "eliminates significant anxiety that a patient may have after receiving a transfusion," said another neurologist, Dr. Paul Wright.

"If indeed someone develops Alzheimer's disease or Parkinson's disease and they had received a transfusion at some point, then based on this study, we can reassure them that it was not from the transfusion," said Wright, chair of neurology at Long Island Jewish Medical Center in New Hyde Park, NY.

Gomolin believes the news is good for blood donors, too.

"Patients with Alzheimer's or Parkinson's disease need not be disqualified as potential blood donors (all other considerations having been addressed)," he noted.

The study was published online June 27 in the journal Annals of Internal Medicine.

More information

The U.S. National Heart, Lung, and Blood Institute has more on blood transfusion.

SOURCES: Paul Wright, MD, chair of neurology, North Shore University Hospital, Manhasset, NY and Long Island Jewish Medical Center, New Hyde Park, NY; Irving Gomolin, M.D., chief, geriatric medicine, Winthrop-University Hospital, Mineola, N.Y.; June 27, 2016, Annals of Internal Medicine, online--Robert Preidt

https://consumer.healthday.com/circulatory-system-information-7/blood-disorder-news-68/donated-blood-won-t-transmit-alzheimer-s-parkinson-s-disease-study-712166.html

Blocking key enzyme halts Parkinson's disease symptoms in mice

June 27, 2016

Researchers at Johns Hopkins say they have gleaned two important new clues in the fight against Parkinson's disease: that blocking an enzyme called c-Abl prevents the disease in specially bred mice, and that a chemical tag on a second protein may signal the disorder's presence and progression. Their work, described online June 27 in The Journal of Clinical Investigation, suggests both a promising target for drug research and a tool that could speed Parkinson's disease research more broadly, they say.

"There were indications that c-Abl activity leads to Parkinson's disease, and our experiments show there is indeed a connection," says Ted Dawson, M.D., Ph.D., professor of neurology and director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. "There is already a Food and Drug Administration-approved c-Abl inhibiting drug in use for leukemia," he adds, "so we're interested in whether it could be used safely against Parkinson's disease or as a starting point to develop other treatments."

Autopsies have revealed that c-Abl is especially active in the brains of people with Parkinson's disease, a progressive disorder of the nervous system that affects movement. Additionally, studies in mice bred to be prone to the disease found drugs that block c-Abl may prevent or slow it. But, says Han Seok Ko, Ph.D., assistant professor of neurology at Johns Hopkins, "the drugs used in those studies could also have been blocking similar proteins, so it wasn't clear that blocking c-Abl was what benefited the animals by either preventing symptoms or influencing disease progression."

The researchers' new experiments started with mice genetically engineered to develop the disease and "knocked out" the gene for c-Abl, a move that reduced their disease symptoms. Conversely, genetically dialing up the amount of c-Abl the mice produced worsened symptoms and hastened the disease's progression. Increasing c-Abl production also caused normal mice to develop Parkinson's disease, the researchers say.

To learn more about how that happened, the team took a look at how c-Abl interacts with another protein, α-synuclein. It's long been known that clumps of α-synuclein in the brain are a hallmark of Parkinson's. The Johns Hopkins researchers found that c-Abl adds a molecule called a phosphate group to a specific place on α-synuclein, and that increasing levels of c-Abl drove more α-synuclein clumping along with worsening symptoms, says Dawson.

"We plan to look into whether α-synuclein with a phosphate group on the spot c-Abl targets could serve as a measure of Parkinson's disease severity," he says. No such objective, biochemical measurement exists now, he notes, which hampers studies of potential therapies for the disease.

Dawson and Ko caution that the use of the anti-leukemia drug nilotinib is not yet indicated for Parkinson's disease patients and that further studies are needed before their results can be applied to clinical care.

About 60,000 Americans are diagnosed with Parkinson's disease each year, and up to 10 million people worldwide are living with the disease, according to the Parkinson's Disease Foundation. 

People with the disease commonly experience tremors; slow, stiff movement; mood disorders; sleep disorders; and other symptoms. Certain gene variants and environmental exposures have been linked to Parkinson's disease, though its causes are still under investigation.

More information: Saurav Brahmachari et al, Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration, Journal of Clinical Investigation (2016). DOI: 10.1172/JCI85456

Journal reference: Journal of Clinical Investigation  

Provided by: Johns Hopkins University School of Medicine

http://medicalxpress.com/news/2016-06-protein-alpha-synuclein-aggregation-parkinson-disease.html?

The National Parkinson Foundation's Moving Day® Walks Fund Parkinson's Programs in Six Cities

National Parkinson Foundation

June 27, 2016

Community Grants Awarded in Atlanta, Boston, Chicago, Los Angeles, Miami, and North Carolina Triangle

MIAMI,  

The National Parkinson Foundation (NPF) is proud to announce that the 2015 fall walk season of Moving Day®, A Walk for Parkinson's, has funded nearly $300,000 in mission services to make life better for people living with Parkinson's and their caregivers in six communities. 

"Moving Day® directly supports local and national services that make life better for people living with Parkinson's and their families," said Paul Blom, NPF's Interim CEO. "At NPF, we are happy to fund our local Parkinson's partners who host programs that help people live well with Parkinson's."

Through monies raised by Moving Day®, a grassroots and fundraising awareness walk, NPF invests in local Parkinson's programs for health, wellness and education programs. Moving Day® also supports NPF's national efforts by investing in the NPF Center of Excellence network that delivers expert care to more than 50,000 Parkinson's patients worldwide; by funding cutting-edge research like the Parkinson's Outcomes Project, aimed at better treatment and care; by providing free patient resources for patients and their families, such as a toll-free Helpline (1-800-4PD-INFO) and the life-saving Aware in Care hospital kit. 

"The NPF Moving Day® grant allows us to establish more exercise classes, add new locations, develop new programs including meditation and theater, and provide more scholarships for free Support and Training to Overcome Parkinson's Disease (StoPD) services to low-income families in the Los Angeles area," said Roberta Marongiu and Alex Montaldo, from StoPD, Inc., a Moving Day® grant recipient. "The Parkinson's community has a voice, and we'll keep working hard to make sure it's heard."

The 2016 community grant offerings focus on: 

• Addressing unmet needs in the Parkinson's community: services for underserved populations, support for clinical trial recruitment for under-represented populations and other unmet needs such as financial barriers to care; 
• Expanding a successful program into a new geography; 
• Developing a new program for people with Parkinson's. 

Community grants from funds raised in the fall walk season are funding local services in each of the following cities:

Atlanta

• PD Gladiators group exercise classes for people with Parkinson's and caregivers at YMCA of Metro Atlanta 
• DREAM's Parkinson's research and education program at Emory University Center for Health in Aging 

Boston

• Rock Steady Boxing at Beth Israel Deaconess Medical Center 
• Women's Parkinson Support Group at Jewish Family and Children's Service 
• Fitness outreach and education program at Boston Jewish Community Center

Chicago

• Educational and Support Outreach Program for Neuropsychiatric Issues in Parkinson's Diseases at Rush UniversityMedical Center 
• Dance program at Hubbard Street Dance Chicago 
• Exercise classes at InspirFit, LLC.

Los Angeles

• Early Speech Therapy Intervention and Improved Survival and Quality of Life at Veteran's Southwest Parkinson's Disease and Research Education and Clinical Center 
• Boxing classes at StoPD, Inc. 
• Exercise programs for body and voice at Re+active Physical Therapy and Wellness 
• 5K training team at University of Southern California

Miami

• LSVT-based physical and speech therapies for Parkinson's and community access by The Neuroscience Centers of Florida Foundation, Inc. 
• Yoga for Parkinson's at Aum Home Shala 
• Rock Steady Boxing at Michael Ann Russell Jewish Community Center 
• Memorial Healthcare System Dance Classes at Memorial Foundation's Fitness Centers 
• Ageless Grace neuroplasticity-based classes by Good Vibes Consultants. 
• Exercise programs at David Posnack Jewish Community Center 
• Virtual Art therapy provided by Art Therapy Consulting and Services 

North Carolina Triangle

• Expansion of ParkNC: Multidisciplinary Parkinson's Care at University of North Carolina at Chapel Hill and state-wide 
• LSVT Big physical therapy program and LSVT Loud speech therapy program at Nash Day Hospital 
• UNC Rex Outpatient Rehab of Wakefield at Rex Healthcare Foundation 
• Music therapy at Atlantic Music Therapy, LLC

Moving Day®, a grassroots fundraising and awareness walk, has raised $11 million since it began in 2011 and is now taking place in 20 cities across the United States. For more information on 2016 Moving Day® walks, visit www.npfmovingday.org. 

About the National Parkinson Foundation (NPF)

Founded in 1957, the National Parkinson Foundation's mission is to make life better for people with Parkinson's disease through expert care and research. NPF has funded more than $189 million in care, research and support services. For more information about NPF, visit www.parkinson.org, or call the NPF Helpline at 1-800-4PD-INFO (473-4636).

About Parkinson's Disease (PD)

Affecting an estimated one million Americans and four to six million worldwide, PD is the second most common neurodegenerative disease after Alzheimer's and is the 14th leading cause of death in the United States. It is associated with a progressive loss of motor control (e.g., shaking or tremor at rest and lack of facial expression) as well as non-motor symptoms (e.g., depression and anxiety). There is no cure for PD and 60,000 new cases are diagnosed each year in the United States alone.

NPF Media Contact:
Leilani Pearl
lpearl@parkinson.org 
305-537-9907

http://www.prnewswire.com/news-releases/the-national-parkinson-foundations-moving-day-walks-fund-parkinsons-programs-in-six-cities-300290585.html

Rolling Momentum

By Jack Cooksey
June 27, 2007
 Adaptive-use trails at Pocahontas State Park open gateways to new experiences for cyclists with disabilities

Even without seeing Billy Moffett, you can sense the emotion swelling in his chest. Over the phone, he tells the story about a sunny Sunday in early April when he went to Pocahontas State Park in Chesterfield County to ride the forested, off-road bike trails with his family. 

He utters one phrase that throws him off as he talks about his father, Bill, pedaling away from him onto a 4-mile segment of trail known as Blueberry Hill. “What happened next ...” Billy Moffett says, and then stops. Overwhelmed by his recollection, he pauses to take deep, hitching breaths.

The 37-year-old then recounts what did occur when his father, a man disabled by Stage 4 Parkinson’s disease, embarked onto a winding trail downhill through the woods. “What happened next was kind of a big moment,” Billy says. He describes his 64-year-old father cranking away with abandon on his three-wheeled mountain bike, also called a “trike.” Bill Moffett's trike allows him to ride in a recumbent position, pedaling with his feet forward.

“He was absolutely on fire. The first mile of that trail is a downhill roller-coaster ride. ... The whole way down that hill, my dad is screaming at the top of his lungs,” Billy recalls. “But it's not the scream of fear. It’s the scream of someone sitting 10 years in a chair.”

Again, he halts — the memory steals his breath. 

That Sunday was an outing Billy Moffett shared with his wife, Erin, and their son, William, who is 4, along with the elder Moffett and his wife, Wanda. Young William is the fifth in a line of William Thomas Moffetts. It was several days before Billy's birthday, and the next day in an effusive Facebook post, he said the experience had delivered him an early, unbeatable gift: the chance to live out his father’s dream to share a mountain-bike ride with his son, a competitive cyclist whom he cheered on for more than 20 years.

Because Bill Moffett's speech is limited by his Parkinson's disease, he asked that his son share their experiences on his behalf.

EXPANDING ACCESS

It was not until 2015 that the Pocahontas mountain biking trail network could accommodate the wider bikes ridden by adaptive cyclists.

The park now has two segments designed for beginner-level mountain bikers, including trike riders. The Gateway 1 and Gateway 2 segments are each about a half-mile long. One is flatter, with smooth, banked turns, gently undulating features, and obstacles that allow newer riders to build skill. The other is also smooth, hard-packed clay and incorporates more elevation change and slightly bigger features.

“It kind of gets people an opportunity to experience what they call a machine-built flow trail,” says Joshua Ellington, the park manager at Pocahontas. Trails like these use sculpted berms to create banking turns for the rider. 

Although the Blueberry Hill segment was not designed specifically for adaptive cyclists, its wider path can work for trikes, too. Its elevation changes and challenging switchbacks make the trail “more intense” than the others, Ellington says.

One of Billy Moffett's longtime cycling friends, Wayne Goodman, largely receives credit for launching the initiative to create such a trail in the region. Goodman is a former president of the region's chief trail-riding group, RVA MORE (Mid-Atlantic Off-Road Enthusiasts). Moffett says that Goodman "built most of the James River [Parks] trail system with his own tools."

In 2010, Goodman had a low-speed bike accident in Forest Hill Park and sustained a spinal cord injury. With recreational therapy services provided at McGuire Veterans Affairs Medical Center, Goodman, a Marine Corps veteran, was eventually back riding, trading two wheels for three. 

Two years later, Goodman enjoined an effort with current RVA MORE president Greg Rollins to create a major “legacy” project that would coincide with the then-approaching 2015 UCI Road World Championships. The legacy project in mind was to establish the Richmond region as a Regional Ride Center, a sort of trail-riding mecca as designated by the International Mountain Biking Association.

To do this, RVA MORE and its partners planned to expand the region’s off-road trail systems to 70-plus miles combined. The effort involved the mountain bike association, the state Department of Conservation and Recreation, the city of Richmond, the Paralyzed Veterans of America's Mid-Atlantic chapter and the Friends of Pocahontas State Park. Together with RVA MORE, the groups coordinated fundraising — toward a reported total of more than $325,000 — and volunteer trail work to expand the state park's already extensive trail network.

Today, the Richmond Regional Ride Center at Pocahontas is drawing more out-of-town mountain bikers to the park, Ellington says, but adaptive cyclists have yet to swarm to the trail system's unique features.“The number of first-time users coming there is actually huge,” Ellington says, noting the  popularity of beginner trails among families with young children, while only a smaller subset of adaptive cyclists seem to be frequent riders in the park. 

“By far, [it is] the most rewarding when we see those hand-cycles over there,” he adds.

OVERCOMING BARRIERS 

Preston Curry, a Paralyzed Veterans of America member who lives in Chesterfield County, stays active through adaptive sports including tennis, lacrosse, rowing, archery and fishing. Curry and many other sports enthusiasts with disabilities find a common resource in the local Richmond-based nonprofit Sportable, which empowers those with mobility challenges to stay active. It’s a quality of life factor that is psychological as much as it is physical, Curry notes.  

The former Army soldier began hand-cycling in 2010. He has competed in various races and began off-road hand-cycling a year ago. "The all terrain part of hand-cycling is new to me," he says. “I'm definitely a rookie, and I'm still learning. I didn't know jack about it until they built a trail.”

Off-road adaptive bikes cost $2,000 to $10,000, according to Moffett. An off-road hand-cycle, for example, is a much different machine from the one that Curry might ride on an open paved path. Many hand-cycles and recumbent bikes allow the rider to sit back, feet first, and crank with their hands or feet.  

Late last year, another mountain biker donated an off-road hand-cycle to Curry, and it requires him to adapt to a new riding position with his head first and legs tucked back. His first time riding at Pocahontas State Park, he says, proved a steep learning curve when he blew out two of his three tires on his ride. 

It illustrates a component of adaptive cycling that is more common to riders like Curry and Bill Moffett: That the barriers to simply getting on the bike and riding in a safe environment are more challenging than for two-wheeled cyclists. 

Curry prefers road cycling on a dedicated path, like the Virginia Capital Trail. Contending with road traffic is not an option because his cycle’s low profile makes it much less visible to motorists than a two-wheeled bike. But the trip from his Chesterfield home to a trailhead in the city requires a serious time investment. He is able to ride closed circuits in a park near his house. 

In the future, he hopes that he can coordinate trail riding with other adaptive-use cyclists through McGuire. Because of the special equipment — he’s still eager to build his skill with it — and the newness of the trails in Pocahontas, he expects it will take time. “So many people are not aware of all-terrain hand-cycling or riding. It might be big in other places, but not here.”

Bill Moffett, like Goodman, is a Marine Corps veteran, and after he had an initial cycling experience on a borrowed incumbent bike, Veterans Affairs staffers helped him gain a grant to get his own trike. His first rides on the Gateway and Blueberry trails in Pocahontas were preceded by “training” rides with his son in city parks so that Bill could build stamina and strength after so many sedentary years. With his new bike, Bill also got busy riding around his neighborhood. “He was just super-stoked about it. He had been just sitting in a chair watching movies for years,” his son says.

Billy Moffett shares his father's sentiment about how necessary and vital it felt to be moving, to ride through the trees that first time on the trail, and to have the wind blowing through his hair.  “It just opened up his world, man... His dream was fulfilled.” 

http://richmondmagazine.com/life-style/rolling-momentum/

Amy Donaldson: Runner with Parkinson's helped me redefine failure and success in 3 brutal miles

By Amy Donaldson, Deseret News

June 26 2016 
PROVO — As I entered the aid station at mile 30, I told the volunteers I was dropping out of the Squaw Peak 50-miler.

The words did not provide the relief I’d convinced myself they would as I grappled with whether I could make the 2:30 p.m. cutoff at mile 33.

By the time they spilled out of my mouth, I had convinced myself I couldn’t make the cutoff. I based this decision on the fact that it had taken me over an hour to run the last three miles.

The brutality of those three miles leading to the aid station where I made my declaration wasn’t the terrain. It was in my mind. So I kept telling myself that if I could just get to the aid station and make the decision official, I’d feel relieved.

I did not.

In fact, when the aid station volunteer heard me she told me I had 50 minutes to get to the cutoff. She said it twice. I vacillated, trying to hide my humiliation and disappointment while desperate for the comfort of a conclusion.

That’s when I saw Celeste Collman.

She was scooping beans into her mouth from a can using a chip as a spoon. Then she poured cold water on her neck and got up to continue the race.

As soon as I recognized her, I told the volunteers I was continuing on to try to make the cutoff. And then I hurried to Celeste's side and asked if I could run with her.

She welcomed me, and we set out into the unforgiving heat and an unrelenting climb. “You probably don’t remember me, but we’ve met,” I said. And then I told her how we’d met two years earlier when my friends and I were training for our first 50-mile race on Antelope Island.

“You gave us some great advice,” I said, as I tried to keep up with her. “Really helpful.”

Almost immediately, I felt overheated.

I had begun to experience symptoms of heat exhaustion during the three miles before I joined Celeste. Recently, I’d been struggling with hydration and electrolytes when running anything over 10 miles. I was frustrated that I couldn’t seem to solve the puzzle my body had decided to throw at me the past few months.

I drank generously and distracted myself by engaging in a conversation with my new friend.

Celeste was all business. And she was all in.

When I said “if we make the cutoff,” she quickly corrected me.

“When,” she said. "Don't talk like that."

And then she laid out the plan. We’d run 50 steps and then walk and then run 50 more. We did this for more than a mile. We talked when we could. We ran in silence when we couldn’t.

She told me that in the year between when I met her and our chance reunion, she’d lost her mom and had been diagnosed with Parkinson's. This was a woman who took up running after beating thyroid cancer in 1995.

“They gave me less than a year to live,” she said. “I was one of those, and this is no kidding. They said it was medullary, the worst kind.” She lived in Florida at the time, and her brother convinced her she’d get better treatment in Utah so she came home.

“I always say when I came from Florida to Utah, God changed the slides in my suitcase,” she said smiling. “Because when I got here they said it was papillary. …Three pathologists made a mistake? I don’t know how they did it. That’s why I say, maybe someone up there changed things.”

She took up running after that — partly to regain her health and partly because her youngest brother ran ultras.

“If my brother could do it, I could do it,” she said laughing.

The 62-year-old Ogden woman, recognizable because she dresses head-to-toe in pink, has run so many ultras, she’s lost count. She has two 100-mile finishes (The Bear 100) and dozens of others, including more than 10 Squaw Peak 50 finishes. So there was no way Celeste was quitting today. And if I could hang onto her, I thought, I can borrow her determination until I recover my own.

I thought the monotony of counting would drive me crazy, but it calmed me. It helped to have a focus and a reward, and it didn’t matter that it was small.

At one point, I was about a quarter mile ahead of her. Then she caught me on a steep incline. As she passed me, we exchanged more chatter. In any other setting it would have been meaningless. On this day, it felt like shelter in a relentless storm.

As the gap between us grew, I looked at my watch. We wouldn’t make it. It wasn’t humanly possible. I was overcome with disappointment. I thought meeting her had been an omen of good fortune. I really thought that if I could stay with her, I’d make it.

She faded from view, continuing her plan, while I abandoned it for self pity. Then I heard her yell back to me, “Don’t you quit, girl!”

And I couldn’t contain a giggle.

How did she know I was contemplating sitting in the shade for just a few minutes? So I sped up. I pushed as hard as I could to catch her. I wanted to at least arrive at the aid station with her.

She politely asked if they’d make an exception, as we were just 12 minutes past the cutoff time. They declined, and she accepted offers of cold drinks and salty foods as she sank into a chair next to me.

She said she was taking care of her terminally ill mother when she began experiencing symptoms of Parkinson's.

“I couldn’t put my hair in a ponytail,” she said, stuttering, another symptom of Parkinson's. “I couldn’t tie my shoes, couldn’t zip up my clothes. I didn’t know. My mom died, and I wasn’t paying attention to myself.”

She admitted it was devastating to hear a doctor tell her she had Parkinson's. But then, she’s been dealt disappointment before.

“I figure, everybody’s got something,” she said with a shrug. “I did pretty good after they gave me dopamine. But it’s getting tougher. Sometimes you have to change the medication.”

The medicine can cause fatigue and other side effects. But she said she’s had some great races in the wake of that diagnosis. When I asked her if signing up for ultras is an act of defiance, she doesn’t hesitate.

“Yeah it is,” she said. “It’s just fun.”

Her disappointment mitigated my own. She’d never failed to finish Squaw Peak. I’d never failed to finish any race I’d started. But I was new to ultra running, and more than once I’d been warned that failure was a necessary part of the growth process.

I’d also let the fact that I’d never failed to finish become a sort of pen. The truth is that I’d stayed safely inside my comfort zone, only attempting races I knew I could finish. So what had I really achieved?

And as I sat with Celeste, sipping cold sodas in someone else’s lawn chairs, I realized how lucky I was that I ran into her that day. I wish we’d made the cutoff, but not because I wanted a medal or the easy confidence that comes with finishing something so challenging.

I wish I’d had the benefit of 17 more miles of wisdom from a woman whose fearlessness and determination make even her failures enviable. She isn't philosophical about it — at all. As we rode to the finish line, she started talking about the ultra she was running in two weeks.

“It’s cheaper than Prozac,” she said with a shrug. “And I’ve got a lot of nice friends from it.”

http://health.einnews.com/article/332888052/bpcEiCPECrNWroWq

Neuron cell death may be caused by overactive immune system: Opening new path of discovery in Parkinson's disease

June 27, 2016

A cell missing the PINK1 protein. NeuroscienceNews.com image is credited to the University of Montreal.

A team of scientists led by Dr. Michel Desjardins from the University of Montreal and Dr. Heidi McBride from the Montreal Neurological Institute and Hospital (MNI) at McGill University have discovered that two genes associated with Parkinson's disease (PD) are key regulators of the immune system, providing direct evidence linking Parkinson's to autoimmune disease.Using both cellular and mouse models, the team has shown that proteins produced by the two genes, known as PINK1 and Parkin, are required to prevent cells from being detected and attacked by the immune system.

When PINK1 and Parkin are dysfunctional, as is the case in a subset of Parkinson's patients, cells display small parts of proteins at their surface, known as antigens, derived from mitochondria. The presence of these antigens at the cell surface causes the activation of immune cells called lymphocyte T cells. These T cells, which can enter the brain, have the ability to destroy any cell displaying the mitochondrial antigens on their surface.

Parkinson's is caused by the death of dopamine-producing neurons in the brain. An overactive immune system due to dysfunctional PINK1 and Parkin genes could explain why dopaminergic neurons die in Parkinson's patients. This indicates that Parkinson's may be one of many autoimmune diseases, including multiple sclerosis, Type 1 diabetes, rheumatoid arthritis, and lupus. An autoimmune disease is one in which the body's own immune system attacks healthy cells.

Researchers suspected that mitochondria, organelles within cells that are responsible for the production of energy and other metabolites, play a role in Parkinson's. It was widely believed that mitochondria become damaged in Parkinson's patients, creating a toxic build-up of broken mitochondria that eventually leads to neuron cell death. However, it has been difficult to provide evidence that this is effectively happening in animal models.

The new findings of the Desjardins/McBride teams linking PD to autoimmune mechanisms, published in the prestigious journal Cell on June 23, have been validated in a mouse model of Parkinson's disease where PINK1 or Parkin are absent.

"Clinicians have shown that the immune system is activated in the brain of PD patients," says Dr. Diana Matheoud, a postdoctoral fellow from the University of Montreal and the article's first author. "Our study explains how an attack by the immune system may be responsible for the destruction of dopaminergic neurons during the disease. We are currently testing whether autoimmune mechanisms lead to the loss of dopaminergic neurons in mice, and developing systems to extend our study to human neurons."

"Antigen presentation was not believed to play a direct role in Parkinson's disease," says McBride. "While most laboratories are following the trail of the 'toxic mitochondria' model, our path led us to observe Parkinson's disease from a different point of view. Our approach, centered on the immune system, led us down a different road where we were able to observe that autoimmunity is likely to play an important role in the progression of the disease."

Now that a link has been established between two key genes involved in the pathology of Parkinson's disease and autoimmune mechanisms, the next step is to develop drugs that can limit the presentation of mitochondrial antigens. Remarkably, the mechanism by which mitochondrial antigens are presented involves a process of vesicle formation, originally described by the McBride group, offering molecular targets for the development of new drugs in an effort to block this process.

The researchers' findings may also lead to better treatments for other diseases. "We think that our study is paradigm shifting because we have identified a new biological pathway linking mitochondria to immune mechanisms in Parkinson's disease. This opens the possibility to use therapies based on modulation of the immune system, something already done for the treatment of other diseases," says Desjardins. "Interestingly, the role played by PINK1 and Parkin in limiting the presentation of mitochondrial antigens may not only regulate a process that impact Parkinson's disease, but may also affect other autoimmune diseases like diabetes and lupus, and primary biliary cirrhosis, where a link to mitochondrial antigen presentation has been observed."

"This paper suggests an entirely novel mechanism by which these recessive, inherited mutations may lead to neurodegeneration," says Jon Stoessl, Professor and Head of Neurology at the University of British Columbia & Vancouver Coastal Health, and former Director of the Pacific Parkinson's Research Centre. "There has been much interest in the potential role of inflammation in PD. Previous studies on Parkin and PINK1 have focused on disruption of mitochondrial housekeeping functions. While the current findings may clearly be related, they suggest an entirely novel approach to the development of targeted therapies. It should be remembered that these are rare causes of Parkinson's disease and the relevance to dominantly inherited and sporadic forms of disease remains to be determined."

http://medicalxpress.com/news/2016-06-neuron-cell-death-overactive-immune.html