Protein problem points to Parkinson’s treatment

February 28, 2018

Canadian research unveils what goes wrong in the brain cells of sufferers. Paul Biegler reports.

The late Muhammad Ali was a high profile victim of Parkinson's disease.

Parkinson’s disease has notched up some high profile scalps over the years, including actor Michael J Fox, former crooner Linda Ronstadt and late great pugilist Muhammad Ali.

But the incurable brain disease, which leaves victims with the shakes, rigid limbs and actions slowed to a crawl, cuts a broad, if more muted, swathe through ordinary society. There are 110,000 Australians living with the disease and their average time from diagnosis to death is little more than 12 years.

New research, however, published in the journal Nature Communications and led by neurobiologist Scott Ryan from the University of Guelph in Ontario, Canada, shines light on what goes awry deep inside the brain cells of sufferers, and may open a door to new treatment.

Parkinson’s kills off brain cells that make dopamine, and it’s the lack of this neurotransmitter that unhinges motor control. Hence those miraculous images of the late neurologist Oliver Sacks “waking up” his frozen patients with the dopamine precursor levodopa, a drug that remains in use today but whose effects are often, sadly, short-lived.

Ryan’s team has shown, for the first time, how a protein called alpha-synuclein – alpha-syn for short – contributes to the death of dopamine-making brain cells. The researchers found that in normal cells a lipid called cardiolipin migrates to the outer wall of the mitochondrion, the cell’s powerhouse, where it folds alpha-syn, origami-like, into a non-toxic shape.

Using stem cells from people with Parkinson’s, the researchers then showed that genetic errors produce a mutant alpha-syn that effectively renders cardiolipin cack-handed. It simply can't wrest the mutant protein into the requisite folded pattern and ultimately, as a result, it wreaks mitochondrial havoc. The mitochondrion undergoes autophagy – literally, it eats itself – and the neuron housing it succumbs thereafter.

Dramatically, the team also showed that mutated alpha-syn is transmitted, virus-like, from neuron to neuron, a process that took just 30 days in mice, and left decimated mitochondria in its wake.

But the researchers also made a discovery that offers hope of a new target for treatment. They raised a type of monoclonal antibody – identical immune cells derived from a single ancestor – against alpha-syn that was able to halt its insidious spread outright.

“Alpha-syn immunotherapy is a promising avenue that warrants further exploration,” the authors write. “Therapeutic approaches that block alpha-syn transmission may have a role as an adjunctive therapy.” 

“Currently there are no treatments that stop nerve cells from dying," says Ryan. “We now have a better understanding of why nerve cells die in Parkinson's disease and how we might be able to intervene.”

https://cosmosmagazine.com/biology/protein-problem-points-to-parkinson-s-treatment

Scientists find reason behind nerve cell death in Parkinson’s disease

February 26, 2018

This is a crucial find considering that the discovery may represent a new target for development of therapies against Parkinson's disease.

Parkinson’s disease is one of the most complicated diseases that humans suffer from and while studies continue towards finding more definite causes and possible therapies, one study has brought us closer to understanding what causes nerve cell death in the disease.Parkinson’s disease is the most common degenerative movement disorder in Canada, affecting about 100,000 people. Published in the journal Nature Communications, the study used stem cells collected from people with the disease. The research team studied how nerve cells try to cope with misfolded alpha-synuclein.

Through the study, a University of Guelph researcher has possibly unlocked the potential for treatment to slow the progression of this fatal neurodegenerative disorder. Prof. Scott Ryan’s research has led to discovery that a molecule inside nerve cells called cardiolipin helps ensure that a protein called alpha-synuclein folds properly. Misfolding of this protein leads to protein deposits that are the hallmark of Parkinson’s disease.

These deposits are toxic to nerve cells that control voluntary movement. When too many of these deposits accumulate, nerve cells die. This is a crucial find considering that the discovery may represent a new target for development of therapies against Parkinson’s disease.

Normally, cardiolipin in mitochondria pulls synuclein out of toxic protein deposits and refolds it into a non-toxic shape. The U of G researchers found that, in people with Parkinson’s disease, this process is overwhelmed over time and mitochondria are ultimately destroyed, said Ryan.

He said understanding cardiolipin’s role in protein refolding may help in creating a drug or therapy to slow progression of the disease.

http://newspharmaceuticals.com/227/cancer-metastases-inhibited-using-novel-steps-in-new-research/

Idaho adventure park hosts special events for Parkinson's

February 26, 2018

Brad Perry visited Urban Air Adventure Park with family and realized it was the perfect place for people who suffer from Parkinson's to be active.

MERIDIAN - When you hear about indoor adventure parks with trampolines, obstacle courses and climbing walls you probably think of it as a place for a kid's birthday party.

But a local man who has Parkinson's saw it as a place to help others with the disease. 

About 60,000 Americans are diagnosed with Parkinson's Disease each year, according to the Parkinson's Foundation.

Brad Perry was diagnosed with Parkinson's three years ago at the age of 33. He's now the Idaho Liaison for the Northwest Parkinson's Foundation (NWPF). 

"I told my self right then and there that I'm not going to let this disease beat me," he said.  "I want to be active. I want to do anything I can. For the most part, I do it for my kids."

Parkinson's is a progressive and incurable neurological condition in which the brain stops producing dopamine, a chemical that regulates movement and moods. The lack of it can cause things like tremors, stiffness and balance issues.While there's no cure, things like exercise help manage it. 

"If you do exercise, even if it's just going out and having fun at a place like this, it triggers our brain to use our dopamine a little bit better," Perry said.

One day, Perry came to Urban Air Adventure Park with family and realized this was the perfect place to be active.  

"By the time I was done playing around I wasn't shaking, twitching and I was actually walking normal again," he said. "I was like 'Hey, if I could get some more people out here they would just absolutely love it.' it's a great alternative to normal exercising and plus you get to feel like being a kid again and who doesn't love that?"

So he put together an event and got the NWPF to team up with Urban Air to encourage people with Parkinson's in the Treasure Valley to come out for the day for exercise and to see they aren't alone.

"In life we all take for granted some of the things we have," said Suraj Jagannathan, owner of Urban Air. "But when there's awareness in what you have and what you can do, it makes you feel great and think about what more can you do  for other people." 

"There are others out there," Perry said. "Embrace it and you'll live a lot longer healthier life and a happier life." 

This is a free event for people with Parkinson's, their families and caretakers. 

Jagannathan said he wants to hold more of these events at his business in the future and will continue to work with the NWPF to do that. 

See video:

http://www.krem.com/news/meridian-adventure-park-hosts-special-events-for-parkinsons-patients/523396966

http://www.krem.com/news/meridian-adventure-park-hosts-special-events-for-parkinsons-patients/523396966

Klobuchar Meets Minnesotans With ALS, Parkinson’s Needing Speech Devices

February 25, 2018

Senator Amy Klobuchar

MINNEAPOLIS (WCCO) — Senator Amy Klobuchar met with Minnesotans on Sunday who will benefit from a billed passed in Washington earlier this month.

The bill helps get speech generating devices, or SGDs, in the hands of people who need them. SGDs assist people with conditions like ALS and Parkinson’s, to help them communicate.

Sen. Klobuchar met with doctors and patients at the University of Minnesota ALS Center.

“Speech generating devices aren’t a luxury for people affected with diseases like ALS and Parkinson’s. They are a life line. And the tools are crucial for helping people to lead independent lives,” Klobuchar said.

Senator Klobuchar first co-sponsored this bill back in 2015. It was set to expire in October, but was renewed when the federal budget bill passed.

Watch video:

http://cbsloc.al/2FwYSyf

http://minnesota.cbslocal.com/2018/02/25/amy-klobuchar-als-parkinsons-speech-devices/

7 Hand Exercises to Help People With Parkinson’s Disease

FEBRUARY 26, 2018  BY WENDY HENDERSON IN SOCIAL CLIPS.

https://youtu.be/Ez2GeaMa4c8

In this video from Invigorate Physical Therapy and Wellness, a physical therapist named Madi demonstrates some simple hand and wrist exercises that may be useful for people suffering from Parkinson’s disease.

The hand and wrist exercises are designed to help Parkinson’s disease patients with fine motor skills like handwriting and dressing, as well as improving flexibility and dexterity. Madi advises that people do the exercises once a day for a period of two weeks to see if they see any improvement in their hand and wrist strength and dexterity. She also recommends patients try to write before and after completing the exercises to see if they notice a difference.

To help warm your hands up for the day ahead, Madi suggests doing the exercises first thing in the morning, before breakfast.

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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.

https://parkinsonsnewstoday.com/2018/02/26/hand-exercises-help-people-parkinsons/

Patient-on-a-Chip Program Could Benefit Parkinson’s Patients by Pinpointing Effective Treatment

FEBRUARY 26, 2018  BY PATRICIA INACIO, PHD

A new personalized medical strategy that can replicate human biological systems in a small chip may help predict patients’ response to certain treatments based on their genetic makeup.

Called Patient-on-a-Chip, the joint initiative by Cedars-Sinai and Emulate combines Cedars scientists’ expertise in stem cell technology with Emulate’s Human Emulation System, which uses Organs-on-Chips technology to re-create true-to-life biology in a chip roughly the size of an AA battery.

To simulate the complex environment inside the human body, each chip has small channels lined with thousands of living human cells. The chip can receive air and fluids, such as blood, to create a microenvironment that mimics that of the human body.

Using stem cell expertise, researchers can take patients’ blood or skin cells and make any organ cell, such as those of a lung, liver or intestine. Most importantly, these cells retain the unique genetic makeup of the patient.

Several practical clinical applications of this technology can be used to benefit patients. By exposing patients’ cells in Organ-Chips to certain therapies, clinicians can gain more accurate information about how a patient would respond and could then tailor a treatment plan to that individual.

“The medical potential of a Patient-on-a-Chip is extraordinary,” Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, said in a press release. “As examples, scientists could use Organs-on-Chips to create a living model of a patient with Parkinson’s disease, amyotrophic lateral sclerosis or Crohn’s disease, a debilitating inflammatory bowel disorder linked to several gene mutations. By flowing drugs through Organ-Chips containing the patient’s own cells and tissue, we could predict which treatment is most beneficial for that patient.”

“By creating a personalized Patient-on-a-Chip, we can really begin to understand how diseases, medicines, chemicals and foods affect an individual’s health,” said Geraldine A. Hamilton, PhD, president and chief scientific officer of Emulate. “The goal of Emulate working with Cedars-Sinai is to advance and qualify the system for new clinical applications and ultimately democratize the technology so that it can have broad impact on patient healthcare.”

A study published last year in the journal Cellular and Molecular Gastroenterology and Hepatology used Emulate’s Organs-on-Chips technology to re-create human intestinal complexity in this small chip.

The study, “Intestine-Chip: A New Model to Understand the Role of the Intestinal Epithelium in IBD by Combining Microengineering Technology and IPSC-Derived Human Intestinal Organoids,” yielded promising data on how organs may respond to different treatments and how the chip could help avoid subjecting the patient to unnecessary and potentially ineffective treatments.

“This project is an important initiative of Cedars-Sinai Precision Health, whose goal is to drive the development of the newest technology and best research, coupled with the finest clinical practice, to rapidly enable a new era of personalized health,” said Shlomo Melmed, MB, ChB, executive vice president of academic affairs and dean of the medical faculty at Cedars-Sinai.

https://parkinsonsnewstoday.com/2018/02/26/cedars-sinai-and-emulate-inc-advance-precision-medicine-with-organs-on-chips-stem-cells/

Chan Zuckerberg Initiative Calls for Parkinson’s Research Proposals

 FEBRUARY 26, 2018 BY JOSE MARQUES LOPES, PHD

The Chan Zuckerberg Initiative is accepting funding applications from researchers who want to do basic science projects on neurodegeneration.

The goal is to increase scientists’ understanding of diseases such as Parkinson’s and Alzheimer’s and attract new talent and ideas.

Grant recipients will become part of the CZI Neurodegeneration Challenge Network, an interdisciplinary collaboration aimed at increasing understanding of the biology that underlies neurodegenerative disorders.

Scientists can apply for two types of funding. One is an CZI Ben Barres Early Career Acceleration Award for researchers who are in the early stages of their work. The other is a CZI Collaborative Science Award. It involves an interdisciplinary collaboration that includes a physician.

Facebook founder Mark Zuckerberg and his wife, Priscilla Chan, started the initiative in 2016. The overarching goal is to cure all diseases before the end of the century.

The program’s focus has been basic research, which can be difficult to obtain funds for because of the long road between laboratory experiments and approval of therapies that arise from them.

Another reason for the basic research focus is that federal spending for such projects has leveled out, according to data from 2015. Federal sources provide less than half of all funding for basic research, compared with 70 percent in the early 1970s.

Scientists have done a lot of research on neurodegenerative diseases in the past several decades. But they need to know a lot more about their underlying biology before they can develop cures.

In Parkinson’s disease, for example, they still do not know why cells that produce dopamine die in a brain region called substantia nigra — and how they die.

The development of treatments for neurodegenerative disorders has led to many complications and a lot of disappointment. In January, Pfizer said it would terminate its research into Parkinson’s and Alzheimer’s after years of unsuccessful results. And in February Merck announced the discontinuation of a Phase 3 clinical trial on an Alzheimer’s treatment, presumably due to lack of effectiveness.

The Neurodegeneration Challenge Network is bringing together outstanding scientists from different disciplines in hopes of shedding light on the basic mechanisms underlying neurodegeneration.

In calling for applications, the Chan Zuckerberg Initiative notes that treatment development efforts “have focused on a relatively narrow set of ideas.” It said it hopes for approaches that reflect a “greater appreciation that these diseases may share common genes, pathways and cellular mechanisms.”

In addition to projects investigating disease mechanisms, it would consider funding the development of animal models that can better mimic neurodegenerative diseases in humans, and projects dealing with non-nerve cells sources of neurodegenerative diseases, such as the immune system.

https://parkinsonsnewstoday.com/2018/02/26/chan-zuckerberg-initiative-parkinsons-research-proposals/

Hope Is Medicine

 FEBRUARY 26, 2018  By "Sherri Woodbridge"

In a conference I attended on Parkinson’s disease a few years back, one of the speakers stated, “Hope is medicine.” In many ways, that is so true. Fyodor Dostoevsky said, “To live without hope is to cease to live.” As a Parkinson’s patient, it may be hard to see, find, or feel hope.

Depression can be one of the first overlooked symptoms while Parkinson’s is making its mark in your life. By the time of diagnosis, you may feel like your whole world has caved in, and diagnosis is like a thousand-ton weight that has just landed on top of you as you lie there in a cave of grief.

One of the hardest things for us to talk about, much less deal with as a people in general, is depression. The difficulty of dealing with it only increases when you have a condition like PD, which can lend itself to making depression a star player. It can take a toll on the relationship between the patient and the caregiver, especially if patients neglect or forget to take “happy pills.” It is my firm belief that if we are not taking care of ourselves emotionally and mentally, it will be a struggle to care for ourselves physically. When our mind is not functioning well, we tend to look at our disease with a somewhat distorted vision, making it even harder than it already is to handle. Often, the distorted view only continues our mental downward spiral.

To those struggling to find anything good in this life with Parkinson’s disease: Are you struggling with an outlook of despair and hopelessness? If so, do you think you may be someone who could benefit from help through an antidepressant? This is nothing to be ashamed of, for having PD is real and so is the depression that clings to it. I have told my husband (my caregiver) that he has my permission to ask (when I feel like giving up in life) whether I’ve missed a dose of my meds. I can, within two missed doses, go from having a good day to wanting it all to end. It’s extremely hard, if not impossible, to care for yourself when your desire to keep going is all but gone. But when that desire to live your life to the fullest in spite of PD is there and healthy, this life can be a wonderful thing.

How can a life with Parkinson’s disease be a wonderful thing? As with any disease, it can make you think twice about your view of life. Your life, in particular. Where you may have once thought of yourself as insignificant, worthless, etc., you now (whether you realize it or not) have found that you are of value. Why else would you seek out a doctor’s care? A support group? Because you matter. You may not have worked through the whys or the hows but somewhere, consciously or not, you have realized that your life means something.

Because your life matters. Your quality of life should matter to the fullest extent of which you are capable.

For example, if you can offer some time to one less fortunate — like reading to a hospital patient or listening to a housebound vet tell of his adventures — do it. Doing activities like this can often remind us that things could be worse, and it always feels good to be able to help another.

If you can sing, sing. It’s good for the heart and especially for those with PD — good for the voice.

If you love to do artsy things, don’t stop because of PD. If you have to change to a different art form, change. Just don’t quit.

Walk, if you can. This is good for the muscles, good for your heart, good for the spirit. If only intentionally around the house, walk.

Talk to someone. When we feel like a burden, we can often shut down. This is when I find it hardest to open up, and when I find it most needful to do. Talk to someone. Let them remind you of the truth — you do matter. They’ll remind you that you are here for a reason and gently ask, “By the way, did you take your happy pill today?”

Living with Parkinson’s disease is hard. It’s a day-to-day battle of pain, a fight for control, and an acceptance for the unwanted. It’s learning how to live a new normal while everyone else continues with the familiar. It’s learning to realize you matter and that there’s a reason you were chosen to carry this load, to walk this path. So, while on this journey they call Parkinson’s disease, take care of you. Take good care of you. And don’t forget to take your meds.

“If you’re reading this…
Congratulations, you’re alive.
If that’s not something to smile about,
then I don’t know what is.”
–Chad Sugg, “Monsters Under Your Head“

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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/2018/02/26/parkinsons-disease-life-hope-medicine-weary-depression/

Discovery reveals way to stop inflammation in Alzheimer's, arthritis, more

February 26, 2018, University of Virginia Health System

Graduate student Michael Schappe (left) and Bimal Desai, PhD, have discovered a switch that could let doctors shut down inflammation. Credit: Josh Barney | University of Virginia Health System

A new discovery about the immune system may allow doctors to treat harmful inflammation that damages the brain in neurodegenerative diseases such as Alzheimer's. It might also let doctors save patients from the potentially deadly inflammation of sepsis, a full-body infection that kills a quarter-million Americans every year.

The finding "opens up a whole new research area to look at neuroinflammation in the context of Alzheimer's and Parkinson's," said lead researcher Bimal Desai, PhD, of the University of Virginia School of Medicine. "But the clinical impact will be in many, many different areas."

Neurological Treatments

Traditional treatments for neurological inflammation, such as in Alzheimer's and Parkinson's disease, are largely ineffective because biological drugs are blocked by what is known as the blood-brain barrier. That barrier protects the brain from dangers such as bacteria or toxins in the blood, but it also makes it very difficult to get drugs into the brain. "A lot of the drugs we use right now to treat inflammation, [known as] biologicals, don't work in the brain because they can't get through," explained Desai, of UVA's Department of Pharmacology and UVA's Carter Immunology Center.

His new finding, involving important immune cells known as macrophages (and microglia), could offer a way around that. He and his team have identified a specific electrical switch, known as an ion channel, within macrophages that controls the flow of calcium into the cells. Without calcium, the cells can't cause inflammation. By targeting this switch with tiny molecules, researchers could deny the macrophages calcium and prevent inflammation - even in the brain.

A Better Way to Battle Inflammation

That could let researchers develop a new and better way to stop inflammation. "Small molecules are perhaps more affordable as treatments and can hit things like this ion channel switch, TRPM7," said researcher Michael Schappe, a graduate student in Desai's lab. "We could use that to address inflammation in a bunch of contexts, but particularly in instances like neuroinflammation, where [current] treatments are particularly ineffective."

Desai noted that drug companies are already at work on drugs that could target this type of switch. And that could be good news for patients with many inflammatory diseases. "Right now, you have conditions like arthritis or IBD [inflammatory bowel disease], where inflammation plays a huge role. They do have very good drugs for them, but these drugs are extremely expensive and cannot be taken orally by the patients. They can cost as much as $20,000 a year," he said. "The reason for that is that they're biologicals. They're protein molecules that are very difficult to make and distribute. But having identified an ion channel as a target in this context allows you to use small molecules, which are ridiculously cheap compared to biologicals and can be taken orally by the patients."

The discovery of the new drug target, the researchers noted, was made possible by something very unusual about UVA.

More information: Michael S. Schappe et al, Chanzyme TRPM7 Mediates the Ca 2+ Influx Essential for Lipopolysaccharide-Induced Toll-Like Receptor 4 Endocytosis and Macrophage Activation, Immunity 2018). DOI: 10.1016/j.immuni.2017.11.026 

Journal reference: Immunity

Provided by: University of Virginia Health System

https://medicalxpress.com/news/2018-02-discovery-reveals-inflammation-alzheimer-arthritis.html

Study uncovers cause of cell death in Parkinson's disease

 February 26, 2018, University of Guelph

A University of Guelph researcher has discovered one of the factors behind nerve cell death in Parkinson's disease, unlocking the potential for treatment to slow the progression of this fatal neurodegenerative disorder.

Prof. Scott Ryan has found that cardiolipin, a molecule inside nerve cells, helps ensure that a protein called alpha-synuclein folds properly. Misfolding of this protein leads to protein deposits that are the hallmark of Parkinson's disease.

These deposits are toxic to nerve cells that control voluntary movement. When too many of these deposits accumulate, nerve cells die.

"Identifying the crucial role cardiolipin plays in keeping these proteins functional means cardiolipin may represent a new target for development of therapies against Parkinson's disease," said Ryan, a professor in U of G's Department of Molecular and Cellular Biology. "Currently there are no treatments that stop nerve cells from dying."

Parkinson's disease is the most common degenerative movement disorder in Canada, affecting about 100,000 people.

Published in the journal Nature Communications, the study used stem cells collected from people with the disease. Ryan's research team studied how nerve cells try to cope with misfolded alpha-synuclein.

"We thought if we can better understand how cells normally fold alpha-synuclein, we may be able to exploit that process to dissolve these aggregates and slow the spread of the disease," he said.

Funded by Parkinson Canada, the study revealed that, inside cells, alpha-synuclein binds to mitochondria, where cardiolipin resides. Cells use mitochondria to generate energy and drive metabolism.

Normally, cardiolipin in mitochondria pulls synuclein out of toxic protein deposits and refolds it into a non-toxic shape.

The U of G researchers found that, in people with Parkinson's disease, this process is overwhelmed over time and mitochondria are ultimately destroyed, said Ryan.

"As a result, the cells slowly die. Based on this finding, we now have a better understanding of why nerve cells die in Parkinson's disease and how we might be able to intervene."

He said understanding cardiolipin's role in protein refolding may help in creating a drug or therapy to slow progression of the disease.

"The hope is that we will be able to rescue locomotor deficits in an animal model. It's a big step towards treating the cause of this disease."

More information: Tammy Ryan et al, Cardiolipin exposure on the outer mitochondrial membrane modulates α-synuclein, Nature Communications (2018).  DOI: 10.1038/s41467-018-03241-9 

Journal reference: Nature Communication

Provided by: University of Guelph

https://medicalxpress.com/news/2018-02-uncovers-cell-death-parkinson-disease.html