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Friday, March 29, 2019

Young-onset Patients, Like This 34-Year-Old Mom, Focus of Parkinson’s Foundation and Awareness Month

MARCH 29, 2019   BY MARY CHAPMAN 






Christina Korines was 22 — a recent college graduate and a newly minted Spanish teacher — when she noticed a tremor in her right foot. That tremor soon progressed into a pronounced limp, and an arm that didn’t swing when she walked.
Something was terribly wrong, she just didn’t know what. Neither did her doctors.
”It was exhausting. It was like my leg wouldn’t listen to my body,” Korines told Parkinson’s News Today by phone from River Vale, New Jersey. “It was like something had sliced me right down the middle.”
Her heart told her it was multiple sclerosis, but that illness was ruled out. One specialist fingered essential tremor; another, generalized anxiety disorder. Still another misdiagnosed her with Huntington’s disease. Next, it was Wilson’s disease.
“My husband said ‘let’s keep looking,’” said the mother of two girls, ages 3 and 7. “So I kept fighting.”
She also kept teaching. But her handwriting had become so small, it was nearly illegible for her students. Her voice turned softer and quieter. She made excuses to avoid walking in her middle-school classroom, and even enlisted the help of an aide.
Still, not knowing what was happening was the most frustrating thing.
One doctor off-handedly broached Parkinson’s disease (PD), but dismissed the prospect because of her age, and she had no known family history of the disorder. But the seed had been planted.
One fateful day in late 2017, she went online and looked up Parkinson’s. Soon, she had an appointment with a movement specialist at NYU Langone Health. What came next was a minor miracle: after 10 years, five neurologists, four MRIs, and seemingly rivers of drawn blood, she finally had a diagnosis: young-onset Parkinson’s disease.

Young-onset PD, relatively rare

“I was totally shocked, but in the most weird way relieved,” said Korines, who immediately began treatment, and quickly noticed improvement. “I feel like that was the start of the rest of my life that day. I knew that I could take control as much as I could, and make a game plan.”
The average age for Parkinson’s onset is typically 60. Only around 4 percent of patientsare diagnosed before age 50; the disease is considered young-onset in people diagnosed before the age of 40. And while the youngest known Parkinson’s patient was diagnosed at 12, Korines has yet to meet a patient under age 72. In her online social media groups, she has come to know a few 40-year-olds.
Christina Korines, a young-onset PD patient, and her family. (Photo courtesy of Christina Korines)
After she was diagnosed and subsequently retired, her husband — a law enforcement sergeant and her high-school sweetheart — persuaded her to sell their house and move with the family to her parents’ home. He wanted to make sure she’d be looked after while he worked.
These days, Korines, 34, is mostly doing OK. While she had no athletic proclivity prior to PD, she’s now totally into non-contact boxing to help manage symptoms.
“When you hit those mitts, the wires aren’t crossed anymore,” she said. “When I walk out, you wouldn’t even know I was sick.”
She does have symptom flair-ups each month, although her tremors are controlled. She tries to lay down during “off periods,” when her medications are wearing off and it’s not yet time for a new dose. Korines also regularly deals with dystonia — repetitive muscle cramping — in one of her feet.
She has problems with comprehension when trying to multitask, she said. But it’s anxiety that really gets her down. Along with depression, the condition is caused in some patients by chemical changes in the brain.
“I’d take any amount more of the physical pain than a second of the anxiety, because of how crippling it is,” Korines said. “It’s ridiculous, it’s absurd, but it’s there.”

Foundation takes the lead

Korines has found fellowship in the Parkinson’s Foundation, which aims to make life better for people with PD by improving care and advancing research toward a cure. Her story, along with other patient narratives, is featured on the organization’s website.
”When you’re so young with Parkinson’s you feel a little lost, but they provided me with support, and just really embraced me,” she said.
John L. Lehr
John L. Lehr has been the nonprofit’s president and CEO for just over two years.  The organization is gearing up for April, Parkinson’s Awareness Month. Toolkits and PD community tips are ready, as are opportunities for patients to share, via videos and photos, inspirational tips and messages. Highlighting the importance of disease awareness, the theme for this year is #KeyToPD.
Some 1 million Americans are thought to have Parkinson’s; Lehr expects that number to reach up to 1.2 million within 10 years. About 10 million people have PD worldwide, he said in a phone interview.
The hiring of Lehr, who has more than two decades of nonprofit fundraising and management experience, followed the merger of two legacy organizations: the National Parkinson Foundation and the Parkinson’s Disease Foundation. On his watch, the newly formed, 100-employee Parkinson’s Foundation has enhanced programming and seen revenue rise by 40 percent.
”What’s so important is the reinvestment in mission programs,” Lehr said. “You always want to do right by the community. It’s a very idiosyncratic disease — no two people have the same course — so we want to make sure it’s not one-size-fits-all.”
About 60,000 new Parkinson’s cases appear annually, he said, much of that owing to better diagnostics. To help address this, the foundation will launch a “newly diagnosed” initiative during April focusing on its 45 Centers of Excellence around the world, including 31 U.S. centers. Beyond setting standards globally, the centers provide expert care to more than 145,000 people.
“It’s going to be a full-court press, including with social media,” he said. “We want engagement early and often.”

The importance of exercise

Lehr said patients with young-onset PD, like Korines, are looking at many years of coping because of the disease’s progressive nature. Those diagnosed in their 60s can live several decades and longer, he said, if they’re proactive.
Still, major science hurdles abound.
“The last 20 to 30 years, we’ve learned a lot,” he said. “But there’s no real therapy, let alone a cure. We don’t know what causes it — genetics, the environment, or some combination. Answers to those big questions will prevent, slow, or even halt the disease.”
One of the foundation’s biggest efforts is its Genetics Initiative, dedicated to using genes to uncover mechanisms responsible for hindering or stopping the disease’s progression. Announced last year, it’s the first national Parkinson’s study to offer free genetic testing plus counseling for Parkinson’s-related genes, including the GBA and LRRK2 mutations.
Its goal is to track the genetic makeup of 15,000 PD patients across 50 U.S. sites within a year, with the first patients expected to be enrolled at six sites in April.
The pilot is an expansion of the Foundation’s ongoing 10-year-old Parkinson’s Outcomes Project. With more than 12,000 participants in five countries, it’s the largest clinical study of PD to date, and acts to help patients better manage their disease and receive better care. It also tracks and reports on research findings, and expects that those enrolled might be more interested in participating in clinical trials.
Along with its array of patient and caregiver support and fundraising efforts, the Parkinson’s Foundation has been busy on other fronts, recently hosting its first medical marijuana and Parkinson’s conference, and creating its first patient-centered research agenda for women.
The most significant Parkinson’s development during his tenure so far, Lehr said, has not been drug or even diagnostic discovery, but rather the heightened awareness of exercise.
“There will always be advancements in therapeutics,” he said. “But the importance of staying active — be it walking, boxing, dancing — and how it functions as good as a drug, has been the biggest news.”
https://parkinsonsnewstoday.com/2019/03/29/young-onset-patients-like-this-34-year-old-mom-focus-of-parkinsons-foundation-and-awareness-month/

A Healthy New Identity Helps When Battling a Chronic Disease

 MARCH 29, 2019    BY DR. C 




Identity, the “I” in CHRONDI Creed, refers to the process of finding a health-fostering identity in the face of a chronic disease that has stolen things we loved to do and caused the death of self. When everything I loved to do was taken from me, all that was left was the time and energy I was putting into managing the disease.
Dealing with chronic disease consumes a large amount of time, and conversations about me were now connected to the disease, including my own self-talk. Without even knowing how, and thinking I should know better, the disease had filled that void created by the death of self. The disease had become my identity, and I hated it. I had to find a healthy new identity to help when battling a chronic disease.
Trying to “find yourself” is tied to one of those great philosophical questions: “What is the nature of human existence?” I have written about this philosophical quest and I thought I had a handle on things, a strong identity of scientist, teacher, and healer. But when the roles I used to make meaning of my existence were stripped from me, I discovered that my intellectual writings provided a thin tether out of the dark void created by the death of self. The actions in my life, the conversations, did not match my identity roles of scientist, teacher, and healer. I needed to reconstruct these identity roles — trying on new hats, looking for one that helps me build a new healthy identity. I needed this new healthy identity to succeed in my battle with a chronic disease.
Getting one’s actions in life, the roles we take on, to match the true self is not an easy thing to do in the face of chronic disease. It takes a commitment of personal resources, courage, and persistence to create new healthy roles to fill the void left after the death of self. It also helps to have support from peers, friends, and family.
But most importantly, you need a fire in the belly, a passion, a purpose that brings meaning from these action roles you will be creating. Then you need to do something every day that will move you one step closer to that purpose-driven life and a healthy identity matching the true self.
I started working on creating these new roles in 1999 when I left all that was my life (home, career) to pursue a PhD — the second-hardest challenge I have faced in my life. I also retrained myself to use the computer as a way of teaching and for a tool in aiding scientific inquiry. In 2006 I applied those skills to a science research project, which, after 13 years, has yielded new discoveries ready to share with the public.
I have also forced myself to become a writer in the humanities by writing as often as time allowed. I forced myself to become a computer-aided graphic artist and taught myself how to design a website. These skills — web design, writing, and graphic arts — helped me to re-establish the multimodal teacher role.
In 2018 I became a column writer for BioNews Services, giving me the opportunity to put the multimodal teacher into action more frequently, hopefully as a role model. Recreating the roles of scientist and teacher, after the death of self, is ongoing for me. Every day is a commitment to these re-created healthy roles as part of building a new identity. It is hard work, but worth it.
The one part of my identity that is still trapped in the void after the death of self is my role of healer. It is a role that is closest to my true nature, my soul. I have received written testimonials from dozens of people who stated that their lives were changed through encounters with this healer role. I miss that contribution to the well-being of individuals and to the collective well-being of society. I am going to try a different hat. It’s a hat with which holding the compassion space for others is expected, and in some ways embraced, so I can bring my experience in doing that and use it — hopefully.
I don’t know what will happen while wearing this new hat. I am just opening the door to new possibilities.
What new hats are you trying? Share your experiences in the comments so others may benefit.
***
Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.
https://parkinsonsnewstoday.com/2019/03/29/identity-chronic-disease-fighting-parkinsons/

ITI-214 Safe, Well-tolerated in Mild to Moderate Parkinson’s Patients, Phase 1/2 Trial Shows

MARCH 29, 2019 BY JOSE MARQUES LOPES, PHD



Treatment with the experimental oral therapy ITI-214 was safe and well-tolerated in patients with mild to moderate Parkinson’s disease, according to a Phase 1/2 clinical trial.
Trial findings also suggested that ITI-214 may ease motor symptoms in these patients.
ITI-214 is a selective blocker of an enzyme called phosphodiesterase 1 (PDE1), implicated in the breakdown of cAMP and cGMP. These two messenger molecules act within cells of the nervous system in response to diverse signals. Because altered PDE1 activity has been reported in both neurological and cardiovascular diseases, blockers such as ITI-214 are intended to restore its normal function.
Work in rodent models suggested that ITI-214, being developed by Intra-Cellular Therapies, may relieve motor and non-motor symptoms of Parkinson’s. In preclinical studies, the investigational therapy also reduced neuroinflammation through its effect on microglia — key immune cells in the central nervous system — and prevented neurodegeneration.
Data from four Phase 1 trials in healthy volunteers showed that treatment with ITI-214 was generally well-tolerated and safe.
Researchers are now presenting clinical data from the randomized, double-blind, placebo-controlled Phase 1/2 trial (NCT03387215) that primarily evaluated the safety and tolerability of increasing doses of ITI-214 in patients with mild to moderate Parkinson’s.
As secondary goals, the seven-day Intra-Cellular Therapies-sponsored study assessed the compound’s pharmacokinetics — its absorption, distribution, metabolism, and excretion in the body — as well as biomarkers of inflammation, and motor and non-motor effects through the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale.
The 40 participants (50 years and older) were maintained on stable Parkinson’s therapy. All five doses of ITI-214 — 1, 3, 10, 30, and 90 mg — were found safe and generally well-tolerated. In addition, the findings showed signals of less motor dysfunction and dyskinesia — involuntary, jerky movements — with some of the administered doses.
“Clinical data indicate that ITI-214 is safe and generally well tolerated across a range of doses in patients with mild to moderate [Parkinson’s],” the scientists wrote.
Noting that the signals of clinical improvement warrant further evaluation, the team added that “selective PDE1 inhibition may represent a novel approach for the treatment of motor and non-motor symptoms associated with [Parkinson’s].”
Of note, all seven of the study’s authors are employees of Intra-Cellular.
Besides Parkinson’s, ITI-214 is being evaluated in a Phase 1/2 trial (NCT03387215) in patients with heart failure, which is supported by results showing increased heart contraction strength in dogs and rabbits.
https://parkinsonsnewstoday.com/2019/03/29/iti-214-safe-well-tolerated-phase-1-2-trial-mild-moderate-parkinsons/

Mouse Studies Suggest Protective Effects of Caffeine in Parkinson’s Disease

MARCH 28, 2019  BY MARISA WEXLER 





Two new studies in mice suggest that caffeine might have protective effects in the brains of Parkinson’s disease patients.
Previous epidemiological studies have suggested that consuming caffeine might protect against the development of Parkinson’s. These more-recent studies set out to test this premise more directly in an animal model.
Both studies used mouse models of Parkinson’s that involved injecting mice with alpha-synuclein. This protein is a major component of Lewy bodies, irregular “clumps” in brain cells that are a hallmark of Parkinson’s pathology. Specifically, both research teams used a mutant form of the protein called A53T, which forms these clumps even more effectively than the wild-type protein.
In both studies, injection with A53T led to changes characteristic of Parkinson’s disease, such as impaired motor function and memory, as well as changes in brain physiology, like the development of the aforementioned Lewy bodies and loss of dendritic spines (parts of neurons involved in making connections in the brain).
However, when the mice were given caffeine in their drinking water, these effects were lessened. Both studies showed similarly beneficial results, though the exact parameters that were measured were different.
In the first study, researchers at Aarhus University, Denmark, report that mice given caffeine had less alpha-synuclein in their brains. Caffeine also caused a three–week delay in the onset of clasping, which is a behavior mice do with their hind limbs that is indicative of brain damage. Furthermore, caffeine-treated mice lived, on average, 40% longer than their counterparts who weren’t given caffeine.
In the second study, researchers at Wenzhou Medical University, China, reported that mice given caffeine had fewer memory problems and more dendritic spines than their untreated counterparts.
Both studies support the previous epidemiological evidence that caffeine can be protective for Parkinson’s disease, although there is the usual caveat that experiments in animal models are never a perfect replica of actual human disease.
It also is not clear why or how caffeine might have such protective effects, and further research will be needed to figure out just how caffeine might benefit Parkinson’s patients.
https://parkinsonsnewstoday.com/2019/03/28/mouse-studies-suggest-protective-effects-of-caffeine-in-parkinsons-disease/

Parkinson’s Patients with Diabetes at Higher Risk of Impulse Control Disorders, Other Issues, Study Suggests

MARCH 28, 2019 BY CATARINA SILVA 



Untreated Parkinson’s patients who also have type 2 diabetes mellitus may be at a higher risk of developing impulse control disorders, severe depression, apathy, and sleep problems, research suggests.
Higher doses of dopamine agonists — which act as a substitute for (or mimic) dopamine in the brain — and longer treatment periods have been seen to make Parkinson’s patients more prone to developing impulse control disorders, including gambling, compulsive shopping, over-eating, and compulsive sexual behaviors.
Evidence indicates that type 2 diabetes increases the risk of developing Parkinson’s disease. Interestingly, an association among type 2 diabetes, depression, and impulse control behaviors has also been suggested.
Researchers from the University of Pécs in Hungary sought to study the impact of pre-existing type 2 diabetes mellitus on Parkinson’s-related non-motor symptoms and on impulse control behaviors in people with Parkinson’s not yet taking prescribed antiparkinsonian medications.
The team performed detailed neurological and neuropsychological examinations on 299 newly diagnosed Parkinson’s patients who were not on any medication.
Of these Parkinson’s patients, 77 (25.8%) had pre-existing type 2 diabetes. Diabetic Parkinson’s patients were older, heavier (with a higher body mass index) and included more men. Importantly, and in comparison to non-diabetic Parkinson’s patients, diabetic patients had more severe depression, apathy, sleep problems and more severe non-motor symptoms, measured by the Non-Motor-Experiences of Daily Living part of the Movement Disorders Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Non-motor Symptoms Scale.
Scientists also reported that 40.3% of Parkinson’s patients with diabetes had impulse control behaviors, which was significantly different from the 22.3% observed in the non-diabetic sample.
Untreated Parkinson’s patients with diabetes were 3.58 times more likely to have impulse control disorders. Due to this, type 2 diabetes mellitus was considered to be an independent predicting factor for the development of these behavior disorders.
Preexisting diabetes may be a risk factor for more frequent impulse control disorders and more frequent and more severe depression, apathy and sleep problems in drug naïve PD patients. However, further prospective longitudinal studies are warranted to study its effects on the disease course,” the researchers concluded.
https://parkinsonsnewstoday.com/2019/03/28/parkinsons-patients-diabetes-higher-risk-certain-issues/

FoxFeed Blog: Research Roundup: New Alpha-Synuclein Therapy Begins Clinical Trial

Posted by  Krishna Knabe, March 29, 2019



The Parkinson's therapeutic pipeline continues to grow as another therapy targeting the protein alpha-synuclein begins human studies. Earlier this month, BioArctic announced that it, along with its partner AbbVie, has begun clinical trials joining seven other alpha-synuclein therapies already being tested by volunteers.
Alpha-synuclein is a priority target for The Michael J. Fox Foundation. There is strong evidence that toxic forms of this protein are involved in Parkinson's disease. We invested early to help treatments targeting alpha-synuclein get off the ground and continue to work with the research community to keep this important area advancing.
BioArctic and AbbVie are testing an antibody called ABBV-0805 at locations in the U.S. It works by binding to toxic clumps of alpha-synuclein and helping remove them. Pre-clinical studies showed that it did remove the majority of these clumps, which led to slower disease progression and reduced motor symptoms.
This new antibody joins seven other promising alpha-synuclein therapies that are already in clinical studies, the final phases of therapeutic development. These therapies, many of which have received support from MJFF, are pursuing different approaches to the target.
Other Antibodies
  • AstraZeneca and Takeda are partnering on a Phase I study of the alpha-synuclein antibody MEDI-1341 in control volunteers in Dallas, Texas. Learn more and get contact information for the trial team.
  • Biogen is testing an anti-alpha-synuclein antibody called BIIB054 in people with Parkinson's in a Phase II trial (called the SPARK study) at sites in Canada, France, Germany, Israel, Italy, Spain, the United Kingdom and the United States. Learn about its eligibility criteria on the study website. You can also connect with your local study site on Fox Trial Finder.
  • Prothena and its partner Roche are testing an anti-alpha-synuclein antibody (PRX002/RO7046015) in a Phase II trial called PASADENA at sites in Europe and the United States. This study finished enrollment late last year and results are expected in 2020.
Vaccine
  • AFFiRiS developed a vaccine called AFFITOPE® PD01A, which instructs our bodies to produce alpha-synuclein antibodies. (This is a similar approach to how the flu vaccine creates protection against influenza). The company is now planning a Phase II trial to investigate the vaccine's efficacy.
Other Therapeutic Approaches
  • Neuropore and its partner UCB developed NPT200-11/ UCB0599, which binds to alpha-synuclein and blocks its accumulation. UCB is planning a Phase Ib study in Europe.
  • Prana Biotechnology began a Phase I trial of its therapy PBT434 in healthy volunteers in Australia last year. This drug works by inhibiting the aggregation of alpha-synuclein and tau proteins through regulation of iron levels. Because it targets several proteins, the therapy is also being studied as a potential treatment for Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP).
  • Proclara is developing NPT088, which can bind to several proteins involved in brain diseases, including alpha-synuclein, amyloid-beta and tau. Proclara is conducting a Phase I trial in people with Alzheimer's. The company plans to test NPT088 in people with Parkinson's as soon as an imaging tool for alpha-synuclein is available.
These eight therapeutics are forging ahead and more are close to reaching clinical trials. Questions about participating in clinical research? View our Trial Participant Pack for videos and a guidebook to learn more about the process and importance of enrolling in studies.

https://www.michaeljfox.org/foundation/news-detail.php?research-roundup-new-alpha-synuclein-therapy-begins-clinical-trial

FoxFeed Blog Teaching Young Doctors about Parkinson's

by  Rachel Dolhun, MD        March 28, 2019





"As movement disorder specialists, one of the most important things we do -- other than care for patients -- is train young doctors," said Steven Frucht, MD, director of the Parkinson's and Movement Disorders Division at NYU Langone. "It has a ripple effect and enormous impact."

Dr. Frucht was co-director of the Fourth Annual MDS-PAS Movement Disorders School for Neurology Residents held in Dallas in early March. This two-day program teaches neurologists in training about Parkinson's and other movement disorders. It also encourages them to consider a career in movement disorders, which allows these physicians to see more people with Parkinson's, learn more about the disease and keep up with the latest research.
In this year's course, 88 attendees from across North and South America learned from 12 world-renowned experts and six patients as well as their fellow participants. Trainees come with a wide variety of experience in and exposure to movement disorders. The program offers opportunities to increase knowledge and skills, ask practical questions about diagnosis and treatment, and examine patients with Parkinson's, Huntington's, cervical dystonia and other diseases. It's also a chance to get advice on how best to pursue a career in the field.
The Michael J. Fox Foundation partners with the Edmond J. Safra Foundation to support this course each year. As part of our commitment to Parkinson's research and care, we are teaching young neurologists about not only the nuts and bolts of Parkinson's but also the incredible momentum in ongoing research. We are increasing the numbers who specialize in the field and can directly meet the needs of people with Parkinson's and their families. And among those who ultimately choose another area of neurology, the course provides important tools to recognize, diagnose and treat Parkinson's. General neurologists, for example, often are the first to make a diagnosis of Parkinson's. And in some areas where there is a shortage of specialists (such as the state of Wyoming, where there is no fellowship-trained movement disorder specialist), they may provide much Parkinson's care.
To address the specialist shortage, MJFF and the Edmond J. Safra Foundation are training more movement disorder specialists. (A movement disorder specialist is a neurologist who has one to two years of additional instruction and education, after neurology training, in diagnosing and treating Parkinson's and related diseases). Each year, The Edmond J. Safra Fellowship in Movement Disorders awards funding to five international medical centers to each train a new movement disorder clinician-researcher (a doctor who also leads research studies) over a two-year period. The program is on track to graduate 26 new movement disorder specialists around the world by the year 2022.
Enormous impact, indeed.
https://youtu.be/xFZJ9Znhrxc

The Fourth Annual MDS-PAS Movement Disorders School for Neurology Residents was made possible with support from the Edmond J. Safra Foundation and The Michael J. Fox Foundation. Acorda Therapeutics, Inc., Boston Scientific, Lundbeck, Medtronic, Sunovion and Sanofi Genzyme provide additional support. While these generous sponsors made the educational offerings possible, their support did not influence content, perspective or panelist selection.

https://www.michaeljfox.org/foundation/news-detail.php?teaching-young-doctors-about-parkinson