Function of gene mutations linked to neurological diseases identified

August 10, 2018, Yale University

VPS13 family members mediate lipid transfer between organelles at membrane contact sites. Bottom left: fluorescence image shows the localization of VPS13C (magenta) at contacts between the ER (green) and a lysosome (blue). Bottom right: fluorescence image showing the localization of VPS13A (magenta) at contacts between the ER (green) and a mitochondrion (blue). Credit: Yale University

Several gene mutations have been linked to Parkinson's disease, but exactly how and where some of them cause their damage has been unclear. A new Yale study, published in the Journal of Cell Biology, shows that one of the genes whose mutations are responsible for a familial form of Parkinson's encodes a protein that controls the transfer of lipids between membranes of cell organelles.

The labs of Yale's Pietro De Camilli and Karin Reinisch investigated the role of VPS13 proteins whose dysfunction play a role in a variety of neurological disorders, including Parkinson's. They found that VPS13 proteins can extract lipids from cellular membranes, harbor them in a waterproof cavity, and transfer them to adjacent membranes. VPS13 family members are localized at sites within the cell where organelles are in close proximity to each other—so-called contact sites—and function as tethers between them making lipid transfer more efficient.

VPS13 family members operate at different sites within the cell and are associated with different neurological disorders. VPS13C, the protein associated with Parkinson's disease, acts at contacts between the endoplasmic reticulum (the organelle where most lipids are synthesized) and endosomes/lysosomes (the organelles where most cell components are degraded). Another, VPS13A, is associated with a Huntington's-like syndrome (Chorea-Acanthocytosis) and acts at contacts between the endoplasmic reticulum and mitochondria, the energy centers of the cell.

As other Parkinson's disease genes also encode proteins of the endo-lysosomal system, the new insight may help identify shared cellular mechanisms in Parkinson's disease resulting from mutations in different genes and thus help design new therapies for this condition, the authors say. Nikit Kumar and Marianna Leonzino of Yale are first authors of the study.

More information: Nikit Kumar et al. VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites, The Journal of Cell Biology(2018). DOI: 10.1083/jcb.201807019

Journal reference: Journal of Cell Biology

Provided by: Yale University

https://medicalxpress.com/news/2018-08-function-gene-mutations-linked-neurological.html

Detailed atlas of the nervous system

August 10, 2018, Karolinska Institutet

Researchers at Karolinska Institutet have created a systematic and detailed map of the cell types of the mouse nervous system. The map, which can provide new clues about the origin of neurological diseases, is presented in the journal Cell. The researchers will now use the same methods to map out the human brain on a detailed level.

The nervous system consists of hundreds, perhaps thousands, of different neurons, but also immune cells, supporting glia cells and cells that constitute vessels and membranes. Our knowledge of these cell types mainly stems from microscopy, which provides information about the shape of cells and can detect certain proteins, and from electrophysiology, where cells are distinguished based on their electrical properties. However, these methods are limited, and there is currently no systematic atlas of the various cell types that make up the mammalian nervous system.

In recent years, Sten Linnarson's research group, and others, have developed methods to map cell types of the brain more systematically in much greater detail than ever before, by measuring gene activity in individual cells.

"You can compare it to the difference between a medieval map and a satellite image: thousands of details that were previously invisible become visible with the use of these new techniques, and the entire map becomes more reliable, explains Sten Linnarson, professor at the Department of Medical Biochemistry and Biophysics at Karolinska Institute.

Largest study of the architecture of the mammalian nervous system to date

His research group now publishes the largest study of the architecture and composition of the mammalian nervous system to date, using the mouse as a model system. The researchers identified 265 different types of cells, and found that neurons had the greatest diversity with over 200 different types. 

"What surprised us most was that we discovered several different types of astrocytes that were specialised in different parts of the brain. This suggests that astrocytes have specific functions in different parts of the brain, and that they play more of a key role in the functions of the brain than previously understood," says Sten Linnarson.

The knowledge of the cell types of the brain can be used to understand the origin of different diseases. Roughly one third of all neurological diseases arise during embryonic development. In the past fifteen years a large number of genetic studies have identified the genes that contribute to diseases such as schizophrenia, multiple sclerosis, autism, Alzheimer's and Parkinson's disease. However, diseases originate from a specific type of cells, in a specific location and at a specific time depending on where and when the relevant genes are active.

Atlas of the nervous system gives clues as to how the disease occurs

With the help of our new atlas of the nervous system, researchers are now able to place disease-causing genes in specific cell types, which provides us with clues as to how the disease occurs. In the long run this might contribute to the development of new drugs or other therapies, says Sten Linnarson.

The mapping of the mouse nervous system is an important first step in a larger project where researchers are now mapping the human brain by using the same methods.

More information: Amit Zeisel et al. Molecular architecture of the mouse nervous system, Cell (2018). DOI: 10.1101/294918

Journal reference: Cell

Provided by: Karolinska Institutet

https://medicalxpress.com/news/2018-08-atlas-nervous.html

With a detailed cell atlas of the mouse brain, scientists gain a new view into the brain's diversity

August 10, 2018 by Tom Ulrich, Broad Institute of MIT and Harvard

Microscope images of brain cells collected for Drop-Seq analysis: neurons. Credit: Arpiar Saunders

Researchers have generated a cellular atlas of the mouse brain, based on the gene expression profiles of nearly 700,000 individual cells covering nine major brain regions.

The new atlas, reported in Cell, provides a window into the brain's remarkable diversity of cells, a starting point for studying how genes and genetic variants contribute to neurological and psychiatric disorders, and insights into how different kinds of neurons achieve their highly specialized functions. All data from the study are publicly available in an interactive analysis portal called DropViz.

"Genetic studies of psychiatric and neurological disorders are now implicating many specific genes, but we need to be able to make the scientific connections from genes to cell populations and circuits," said study senior author and Broad institute member Steven McCarroll, the director of genetics at the Stanley Center for Psychiatric Research and the Dorothy and Milton Flier Professor of Biomedical Science and Genetics at Harvard Medical School. 

"Historically, months of experiments were often required to figure out which cell populations express even one of these genes. By creating a data resource like this—in which scientists can simply look these things up online—we hope to enable a stronger understanding of how brain illness arises in specific cell populations."

Microscope images of brain cells collected for Drop-Seq analysis: astrocytes. Credit: Arpiar Saunders

Genetic studies are identifying growing numbers of genes and genetic variants associated with psychiatric or neurological disorders. However, understanding which variants matter in which cell types, and how they relate to healthy and disease states, remain among the greatest challenges in neuroscience and neuropsychiatric research.

And while scientists have a general idea of the different types of cells that make up some brain regions, the detailed identities, molecular repertoires, and functional roles of cells at a brain-wide level have yet to be fully cataloged, further complicating efforts to link variant to cell to function.

"We haven't had a global framework for understanding, at the molecular, single-cell level, the cells that make up the core components of the brain," said Arpiar Saunders, a postdoctoral researcher in the McCarroll laboratory and co-first author of the study with Stanley Center associate member and Massachusetts General Hospital psychiatrist Evan Macosko. "We wanted to produce an unbiased characterization of the brain's diversity within key regions."

Microscope images of brain cells collected for Drop-Seq analysis: oligo- and polydendrocytes. Credit: Arpiar Saunders

The research team generated the atlas by analyzing gene expression in 690,000 individual cells isolated from nine brain regions, including the frontal and posterior cortex, hippocampus, cerebellum, thalamus, striatum, and substantia nigra. All told, the nine regions account for between 60 and 70 percent of the volume of the mouse brain.

To analyze so many cells, the team used Drop-Seq, a high-throughput, microfluidics-based, single-cell RNA-sequencing method developed by Macosko and collaborators in 2015 when he was a postdoctoral fellow in McCarroll's laboratory.

First, however, the team had to collect individual cells from the adult mouse brain in a way that reflects the cellular diversity of native, intact tissue. This is no small feat, given that adult brain cells weave together in a dense, complicated fashion as they age, making them difficult to tease apart. The team therefore adapted existing "patch-clamp" physiology protocols originally designed for making electrical recordings from single neurons.

"It's very hard to keep cells healthy as you dissociate them, especially in adult models," Saunders explained. "We replicated certain aspects of the brain's environment, but also left out key ingredients to help the cells avoid self-induced shock. We also optimized our protocol for each brain region individually."

Microscope images of brain cells collected for Drop-Seq analysis: neurons (pink), astrocytes (green), oligo- and polydendrocytes (blue). Credit: Arpiar Saunders

The team also developed a new computational framework for analyzing their data based on independent component analysis (ICA), enabling them to easily detect and compare many types of biological signals, as well as technical artifacts, which could be filtered from the data.

"You can think about transcription like a mixture of conversations in a crowded room," Macosko said. "ICA is very good for finding signals, or individual conversations, if you will, within a sea of noise."

By analyzing the gene expression patterns in their data, the researchers distinguished 565 different cell populations, including a wide variety of neurons and non-neuronal cell types, including glial, immune, and blood vessel cell types.

Among them were new cell types never before detected. For instance, the data revealed the existence of a rare subtype of neurons, which the team dubbed "eccentric" spiny projection neurons (or eSPNs), in a brain region called the striatum. This neuronal crossroads is involved in motor control and habit formation, and is affected by neurodegenerative disorders such as Huntington and Parkinson diseases.

"eSPNs are, molecularly speaking, very different than the major SPN populations, which have been studied for decades," Saunders noted, adding that eSPNs make up only about 4 percent of the SPNs in the striatum. "Because eSPNs express many of the same canonical molecular markers as other SPN populations, they were genetically camouflaged within these larger striatal SPN populations."

"This is where unbiased, high-throughput approaches like Drop-Seq are important, because you would otherwise never see this cell population," Macosko added. "We had to sample thousands of cells in order to detect and describe them."

The data also let the researchers look for both common and rare transcriptional programs within and between cell types and brain regions. For example, the team discovered a previously-uncharacterized genetic program they called the neurofilament program, which appears to support the formation and function of neurons' axons (their long output arms) and presynaptic terminals (the axon tips, which release neurotransmitters to pass signals on to other neurons).

Taken together, the data provide a complete transcriptional repertoire for each of the nine regions studied, a lookup table for examining where in the brain individual genes are relevant, and a baseline for studying psychiatric and neurological disorder-associated genes in mouse-based model systems.

To give their findings as broad utility as possible, the team has made all of their data publicly available in a searchable, interactive, web-based portal called DropViz.

"We spent a great deal of time stringently curating our findings so that DropViz users can easily find information that is relevant to the biology they want to study," Saunders said. "It was exhausting, an almost single-cell-brain-Crossfit kind of effort, but we think it helped strengthen our confidence in the nuances of the data. There are thousands of interesting leads for the functional neuroscience community to pursue."

More information: Arpiar Saunders et al. Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain, Cell (2018). DOI: 10.1016/j.cell.2018.07.028

Journal reference: Cell 

Provided by: Broad Institute of MIT and Harvard 

https://medicalxpress.com/news/2018-08-cell-atlas-mouse-brain-scientists.html

By Parkinson’s Disease Support Group

August 9, 2018

POCATELLO — The Parkinson’s Disease Support Group will meet Monday at 11 a.m. at Monte Vista Hills Healthcare Center, 1071 Renee Ave in Pocatello.

At our support group meeting this month, we will have information on upcoming events and activities, including programs of interest to those with Parkinson’s or that have an interest in Parkinson’s. We will also have presentations from Davis Phinney Foundation’s Every Victory Counts. We invite you to come prepared to share ideas for future programs, success stories, information, etc.

Anyone with an interest in Parkinson’s support group activities are invited, including caregivers and providers. For additional information, contact Spencer at 208-604-3393 or stuckisk@gmail.com or Kim at 208-233-1411, ext. 224.

https://idahostatejournal.com/community/parkinson-s-disease-support-group-to-meet-monday/article_0fab32c7-b030-5e36-9cf3-a9f98253ac3e.html

Alzheimer’s: Link Between Dementia and Eye Diseases Discovered

NEUROSCIENCE NEWS     AUGUST 8, 2018
Source: University of Washington Health Sciences.

A new study reveals a considerable link between three common eye diseases and an increased risk of developing Alzheimer’s disease. Researchers believe their findings could help physicians better detect those at risk of developing dementia.

Lee said anything happening in the eye may relate to what’s happening in the brain, an extension of the central nervous system. NeuroscienceNews.com image is in the public domain.

Alzheimer’s disease is difficult to diagnose as well as treat, but researchers now have a promising new screening tool using the window to the brain: the eye.

A study of 3,877 randomly selected patients found a significant link between three degenerative eye diseases – age-related macular degeneration, diabetic retinopathy and glaucoma – and Alzheimer’ disease.

The results offer physicians a new way to detect those at higher risk of this disorder, which causes memory loss and other symptoms of cognitive decline. .

The researchers, from the University of Washington School of Medicine, the Kaiser Permanente Washington Health Institute and the UW School of Nursing, reported their findings Aug. 8 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

“We don’t mean people with these eye conditions will get Alzheimer’s disease,” said lead researcher Dr. Cecilia Lee, assistant professor of ophthalmology at the UW School of Medicine. “The main message from this study is that ophthalmologists should be more aware of the risks of developing dementia for people with these eye conditions and primary care doctors seeing patients with these eye conditions might be more careful on checking on possible dementia or memory loss.”

The participants in the study were age 65 and older and did not have Alzheimer’s disease at the time of enrollment. They were part of the Adult Changes in Thought database started in 1994 by Dr. Eric Larson, who is at Kaiser Permanente Washington Health Research Institute.

Over the five-year study, 792 cases of Alzheimer’s disease were diagnosed by a committee of dementia experts. Patients with age-related macular degeneration, diabetic retinopathy, or glaucoma were at 40 % to 50% greater risk of developing Alzheimer’s disease compared to similar people without these eye conditions. Cataract diagnosis was not an Alzheimer’s disease risk factor.

“What we found was not subtle,” said Dr. Paul Crane, professor of medicine, Division of General Internal Medicine, at the UW School of Medicine. “This study solidifies that there are mechanistic things we can learn from the brain by looking at the eye.”

More than 46 million older adults are affected by dementia worldwide and 131.5 million cases are expected by 2050, the researchers said. Alzheimer’ disease is the most common dementia,and discovering risk factors may lead to early detection and preventive measures, they said in their paper.

Lee said anything happening in the eye may relate to what’s happening in the brain, an extension of the central nervous system. The possible connections need more study. She said a better understanding of neurodegeneration in the eye and the brain could bring more success in diagnosing Alzheimer’s early and developing better treatments.

The researchers said several factors suggest the effects they uncovered were specific to ophthalmic conditions and not merely age-related phenomenon.

Larson said for years Alzheimer’s researchers were focused on amyloid buildup in brain tissue, but that hasn’t brought much benefit to patients.

“This paper is pointing to a new area of opportunity,” he said.

About this neuroscience research article

Funding: The study was funded by National Institutes of Health, NIH/National Institute of Aging, NIH/National Eye Institute, Research to Prevent Blindness, UpToDate.

Source: Bobbi Nodell – University of Washington Health Sciences

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: Open access research for “Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease” by Cecilia S. Lee, Eric B. Larson, Laura E. Gibbons, Aaron Y. Lee, Susan M. McCurry, James D. Bowen, Wayne C. McCormick, and Paul K. Crane in Alzheimer’s & Dementia. Published August 8 2018.

doi:10.1016/j.jalz.2018.06.2856

---

Abstract

Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease

Introduction

Identifying ophthalmic diseases associated with increased risk of Alzheimer’s disease (AD) may enable better screening and understanding of those at risk of AD.

Methods

Diagnoses of glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) were based on International Classification of Diseases, 9th revision, codes for 3877 participants from the Adult Changes in Thought study. The adjusted hazard ratio for developing probable or possible AD for recent (within 5 years) and established (>5 years) diagnoses were assessed.

Results

Over 31,142 person-years of follow-up, 792 AD cases occurred. The recent and established hazard ratio were 1.46 (P = .01) and 0.87 (P = .19) for glaucoma, 1.20 (P = .12) and 1.50 (P < .001) for AMD, and 1.50 (P = .045) and 1.50 (P = .03) for DR.

Discussion

Increased AD risk was found for recent glaucoma diagnoses, established AMD diagnoses, and both recent and established DR. People with certain ophthalmic conditions may have increased AD risk.

https://neurosciencenews.com/alzheimers-eye-disease-9672/

GARCINOL - A FUTURE MAO INHIBITOR FOR PARKINSON'S DISEASE

8th August 2018

MAO inhibitors are often prescribed for Parkinson's Disease. MAO inhibitors help to maintain dopamine levels by inhibiting the enzyme Monoamine Oxidase (MAO). It is primarily low dopamine levels that cause Parkinson's Disease. The main MAO inhibitors in use are selegiline, rasagiline and safinamide. 

For more information go to selegilinehttps://www.rxlist.com/eldepryl-drug.htm, rasagiline 

https://www.rxlist.com/azilect-drug.htmand safinamide 

https://www.rxlist.com/xadago-drug.htm Researchers have assessed Garcinol, which originates from plant species. 

For more information go to : garcinolhttps://www.drugs.com/npp/garcinol.html

The present study identified Garcinol as a potential candidate in the treatment of Parkinson's Disease by virtue of its exorbitant MAO-B inhibitory potential. The inhibitory potential is comparable to the known MAO-B inhibitors, which was evaluated using molecular docking technique.

Additionally, Garcinol was found to have potential as a COMT inhibitor, which the existing MAO inhibitors don't have. COMT inhibitors are another type of Parkinson's Disease drug. It was also found to have known antioxidant and anti-inflammatory potential.

Reference : Medical Hypotheses [2018] 117 : 54-58 (M.K.Mazumder, R.Paul, B.C.Phukan, A.Dutta, J.Chakrabarty, P.Bhattacharya, A.Borah)

Complete abstract : http://www.ncbi.nlm.nih.gov/pubmed/30077198

http://www.viartis.net/parkinsons.disease/news/180808.pdf mail@viartis.net

Parkinson’s disease - the 99p snack you should eat everyday to boost brain health

By Matt Atherton  August 9, 2018

PARKINSON’S disease symptoms develop gradually over a period of time, and it’s caused by nerve damage in the brain. Adding this snack to your diet every day could improve brain health, and reduce signs of the neurodegenerative condition.

Parkinson's disease: Reduce signs and symptoms of brain condition by adding walnuts to your diet (Image: GETTY Images)

Parkinson’s disease is a condition where the brain becomes progressively more damaged over time.

It’s caused by a loss of nerve cells in part of the brain. The nerve cells are responsible for producing dopamine, a chemical that sends messages between the brain and nervous system.

Making some small diet changes could help to reduce symptoms of Parkinson’s disease.

Snacking on walnuts could boost patients’ brain health, according to charity the Parkinson’s Foundation.

Parkinson’s disease: Reduce symptoms with walnuts in your diet 

Walnuts help to promote brain health, which is crucial for Parkinson’s disease patients, as the condition is caused by a gradual decline in brain function.

Just a small portion of walnuts could reverse the brain’s ageing process, while improving memory and learning.

The nuts’ antioxidant properties are believed to be behind their benefits for Parkinson’s patients, added Parkinson’s Life.

The antioxidants work by combatting damage to brain cells, which can be caused by harmful free radicals, it said.

The Parkinson’s Foundation said: “The right foods will also optimise your medications, keep your bones strong, fight constipation and weight loss and maintain general health and fitness.

“While there is no prescription for a Parkinson’s disease-specific diet, to maintain overall good health most people living with Parkinson’s disease should eat a variety of whole grains, vegetables, fruits, milk and dairy products, and protein-rich foods such as meat and beans.

https://youtu.be/3n8UjH9h_8I

Tremor - One of the most noticeable signs of Parkinson's is a tremor that often starts in the hands or fingers when they are relaxed

“Snack on small quantities of walnuts, cashews and other nuts to promote brain health.”

Parkinson’s Life added: “Even a small portion of walnuts in our daily diet can reverse the brain’s ageing process and improve learning, memory and motor coordination.

“Researchers attribute the benefits to their anti-oxidant properties, which may combat damage caused to brain cells by free radicals.”

Parkinson’s disease patients should also be sure to drink enough water - about six glasses a day - and to eat fibre-rich foods, the charity said.

Brown rice and whole grains are excellent sources of fibre. Eating more fruit and beans could also help to relieve digestive difficulties and constipation, it added.

Parkinson's disease: Walnuts could be beneficial for the brains of patients

Signs of the condition are mild in its earlier stages, but develop gradually over a period of time.

The most common Parkinson’s disease symptoms include tremors, slow movement, and stiff muscles.

The brain condition could also lead to nerve pain, balance problems, and a loss of sense of smell.

Supportive therapies, medication or surgery may be suggested to Parkinson’s disease patients.

Speak to a GP if you’re worried about the signs of Parkinson’s disease.

https://www.express.co.uk/life-style/health/1001390/parkinsons-disease-symptoms-diet-walnuts-brain

Michael J. Fox on Parkinson’s, Overcoming Fear and the Race for a Cure

Malina Saval   August 9, 2018

It’s a cool june afternoon in New York and Michael J. Fox is sitting in his Upper East Side office, his dog, Gus, a lumbering rescue mutt — Great Dane, hound, Chow, some Lab — napping underfoot. The pale gray walls are decorated with rustic signs from some of Fox’s favorite vacation spots — Vermont, Martha’s Vineyard — and a photo of Fox and Boston Bruins hockey great Bobby Orr is propped up on a bookshelf, along with Fox’s Emmys and Golden Globes and his Grammy award for spoken word album, an adaptation of his 2009 memoir “Always Looking Up: The Adventures of an Incurable Optimist.”

Fox, who is being honored by Variety as philanthropist of the year for his work on Parkinson’s disease research, is deeply optimistic at 57. A military brat raised on various bases across Canada, Fox was a plucky, free-spirited kid, prone to recklessness and adventure. At school and at home, he was willful and precocious, never doubting that someday he would make a name for himself.

“I was built to overcome,” says Fox, a nod to both his short stature and emotional tenacity. “I was built to survive.”

By his mid-20s, the gifted comic actor was a bonafide star, capturing America’s attention as brash Reaganite Alex P. Keaton on “Family Ties” before securing worldwide fame as time-traveling teen Marty McFly in the “Back to the Future” trilogy. By 1985, Fox was everywhere, a Hollywood heartthrob featured on the covers of magazines ranging from Tiger Beat to GQ. Fox’s celebrity became so explosive that he and wife, actress Tracy Pollan, whom Fox met while shooting “Family Ties,” married under the whir of paparazzi helicopters overhead. There were sports cars and boozy soirees and a slate of big-screen projects in which Fox would take a dramatic turn, from “Bright Lights, Big City” to Brian De Palma’s “Casualties of War.”

“It was all a big party,” says Fox. “It was all about me and what I would do and what I was going to do and what I had done and what I could remember doing last night.”

That changed one Tuesday morning in November 1990. Fox was in Gainesville, Fla., filming “Doc Hollywood” when he awoke in his hotel room to a raging hangover and a relentlessly twitchy pinky finger that presaged a life-changing medical diagnosis: “The doctor told me, ‘you have Parkinson’s disease.’”

Parkinson’s, a progressive nervous system disorder that affects movement and is characterized by tremors, muscle rigidity and changes in speech, as well as a host of other debilitating symptoms, is typically diagnosed in patients around the age of 60. Of the roughly 6 million people worldwide (1 million in the U.S.) fewer than 10% are diagnosed with young-onset Parkinson’s at age 50 or younger. Linda Rondstadt, Alan Alda and Leonard Maltin were all diagnosed well past their 50th birthday; Fox was diagnosed at the age of 29.

“I got this diagnosis, and it freaked me out, and I ran from it,” says Fox. “I drank to obliterate it, to make it go away.” Then he reached a point where he decided to try and deal with the disease, asking himself, “why don’t I just try to understand what it’s telling me, what it means?’ I said, ‘I need to learn more about this.’ And after it was alarming and freakish and scary and nightmarish, Parkinson’s was settling. I was able to accept the fact of it, accept the truth of it. But acceptance doesn’t mean resignation; it means accepting and then moving on.”

In 1998, during his run on the hit ABC sitcom “Spin City,” Fox revealed his diagnosis publicly. Overnight, he became the face of a disease that had thus far been lost in the shadows, considered by society to be a “shaky old person’s disease.” Fox testified before Congress, urging the government to allocate more funding for Parkinson’s research. He reached out to the Parkinson’s community and the Parkinson’s foundations already in existence and saw what they were accomplishing, and also what was missing.

Fox went from believing his life was over to thinking “not only can I live with this, but I need to commit to this community and take advantage of the attention that I get. Whether it’s bidden or unbidden, it’s there and it’s powerful.”

In 2000, Fox left “Spin City,” for which he won his fourth lead actor Emmy, and dove full time into his newfound role as activist. Later that year, he established the Michael J. Fox Foundation for Parkinson’s Research. To date, MJFF, with foundational partnerships in Europe, Asia and North America, has funded more than $800 million in research grants and projects worldwide, more than any other Parkinson’s foundation of its kind.

Michael J. Fox became a star on “Family Ties,” left, and exited “Spin City,” above right, to work on his Parkinson’s foundation.

“I wanted to identify the research and have the money go out right away,” says Fox of MJFF’s driving philosophy. “I wanted to inspire scientists to do the work now. We’re not here to sit on the money, we’re here to put it out. And it’s just fantastic because it’s grown from just that instinct to immeasurable heights and dynamically new possibilities.”

With a staff comprising pioneering neuroscientists, research scientists, public policy experts and geneticists, MJFF has launched and sustained myriad breakthrough initiatives that have radically changed the face of Parkinson’s disease research, propelling the medical and scientific communities closer to a cure. The foundation provides webinars and seminars for patients and their caregivers.

From Fox Insight, an online clinical study designed to amplify patient voice in Parkinson’s research, to Team Fox, a grassroots community fundraising program that spawns such nationwide events as Fox Trot 5K walk/runs and Pancakes for Parkinson’s breakfasts, MJFF is 100% patient-focused, empowering individuals to play an active role in combating the disease.

“[Michael] has led by example to be engaged and not just to say ‘I have Parkinson’s,’ but this is what we can do as a community,” says Deborah W. Brooks, MJFF co-founder & executive vice chairman. “And it’s really him as a peer speaking to other peers, whether it’s a Parkinson’s patient or their families or our organization as a whole. 

Our whole organization is part of that voice, which is, that this is not something that happens to you and then you sit by idly and hope good things fall from the sky, but that there are a variety of ways in which patients and families can step into this and be active. He has become such a role model and our organization has really become a platform for many, many patients and families to not be passive observers.”

That people are even talking about Parkinson’s on such a global scale is revolutionary, and an advancement for which Fox and the foundation deserve credit. Wherever Fox goes in the world, whether it’s Greece on vacation, or Sweden, where the Karolinska Institute awarded him an honorary doctorate in medicine, he’s bringing knowledge of the disease to people in those countries.

More than that, he’s bringing them hope.

It’s important to Fox that he communicates information about the disease without people feeling uncomfortable. “I want to say to them, ‘I know what you’re thinking. It’s OK,’” he says. “We’re always afraid of stuff we don’t understand. People would look me in the eye and say, ‘how are you?’ and expect to see fear in my eyes and they just see their own fear reflected back at them. It didn’t make me angry, it made me feel kind of responsible. I want to relieve people of that burden so we can get to the conversation. We give these people as much as we can. We’re sharing this. This [foundation] is an act of fellowship.”

What makes Parkinson’s tricky to treat, and somewhat complicated to approach, is that no two patients with the disease suffer alike. It manifests itself in a variety of nefarious ways. Where depression and anxiety might strike one person, another might develop digestive function problems, cognitive issues or insomnia. While there are genetic links — there are clusters, for example, within the Ashkenazi Jewish community — the cause of the disease is unknown. As people continue to live longer, scientists predict the global prevalence of Parkinson’s to double by 2040, making the foundation’s work ever more urgent.

“Everyone’s got their own disease, everyone’s got their own Parkinson’s. It’s to the point where we suspect it’s a number of different diseases,” says Fox, who takes L-Dopa, a dopamine-replacement medication, to help control his tremors and shakes. Sometimes it works well, other times it wears off too quickly. “Sometimes, I have too much dopamine,” says Fox. “I miss the mark. I miss my timing.” Like most drugs, L-Dopa carries with it adverse side effects, another motivating factor in MJFF’s search for cutting-edge treatments.

“One thing we’re super excited about is that in the last 10 years we’ve seen a lot of new drugs being tested in the clinic and a lot of new drugs on the market,” says Brian Fiske, MJFF senior vice president, research programs. “A lot of them are a twist on what we have, optimizing delivery of the dopamine medication. And there are new drugs on the market that aren’t classically thought of as Parkinson’s medications. They are treatments directly targeted toward lesser-known symptoms and side effects of the disease. With all this R&D activity, there is tremendous cause for hope and optimism about what’s to come in our ability to improve treatment options for people with Parkinson’s in the near future.”

One of MJFF’s latest and most breakthrough programs is its Parkinson’s Progression Markers Initiative, a landmark clinical study to identity biomarkers of Parkinson’s disease. Biomarkers are disease indicators that are critical missing links in the search for better Parkinson’s disease treatments.

“After it was alarming and freakish and scary and nightmarish, Parkinson’s was settling.”

Michael J. Fox

“We are getting closer to being able to recognize the disease before symptoms are evident and treat it early,” says Fox. “And I love this idea that you could still have Parkinson’s, but it never gets to the point where it’s obvious, where it’s symptomatic, where we try to figure out how to fix this wreck, how to prevent the wreck before it happens. 

People will say to me, ‘are you going to find a cure in time for you?’ I say, ‘I honestly don’t think about it.’ It’s essential that we find a breakthrough, period. I’m just put in a position where I can help motivate people in the scientific community and the patient community to solve this problem before future generations wake up at 57 and find they are in this situation.”

And while Fox’s situation is not without its challenges, there is also great beauty, as evidenced not only by the success of the foundation, but his three best-selling books and kudos-filled career as an actor. Since his diagnosis, Fox has won a guest actor Emmy for his recurring role as a wheelchair-bound drug addict on FX’s “Rescue Me”; played a manipulative attorney with dyskinesia (a Parkinson’s-like movement disorder) on the hit CBS drama “The Good Wife,” earning yet another Emmy nom; and played a news anchor with Parkinson’s disease on NBC’s “The Michael J. Fox Show.” Most recently, Fox completed a five-episode arc as Ethan West, a conniving, shark-like power attorney, on ABC’s “Designated Survivor.”

“I love to show that people with disabilities, that people with Parkinson’s can be assholes, too,” says Fox. “And that’s important. I feel for the disabled community and I feel part of that community. We are fully rounded people, we just have this issue that we deal with.”

Fox’s life, he maintains, is punctuated by joy. “I’m a lucky man,” he says, and that’s not despite his illness, but, at least in part, “because of it.” The foundation, and its mission to help millions of people, has infused his life with meaning.

Each year, Fox plays guitar at MJFF’s fundraising gala, strumming Chuck Berry’s “Johnny B. Good” (a reference to his role in “Back to the Future”) with the likes of Chris Martin and Brad Paisley. He plays golf and is working on a fourth book. “I literally wear out the rug,” he jokes of his writing process, which includes pacing the floor and dictating to a writer’s assistant. More than anything, he says, it’s his family — Pollan and their four children — on whom he relies for strength and inspiration.

“If I were to use one word to describe my kids it’s kind. They are really kind people,” says Fox, tearing up. “They take it in, it’s just natural. It just is what it is. I don’t know how we got so lucky that they turned out that way but they apply that to everything they do. They didn’t get anxiety from [my Parkinson’s]. They got peace from it. And it’s kept them honest. They pour orange juice for me. It’s great. You understand there’s bigger stuff going on than just yourself. Compassion is really important, and empathy and understanding and openness. You boil it down to what’s important now, what’s important in that moment.”

As the Michael J. Fox Foundation strives tirelessly to find a cure for Parkinson’s, Fox’s advice for others living with the disease is “to accept it, to own it.”

“There’s no good answer for how to deal with Parkinson’s,” he says. 

“There’s no flat thing. You experience it and you push through it and you try to make as many friends as you can along the way. You can’t depend on other people’s kindness, but in recognizing it’s in there you can elicit it. So why have a glib outlook?” he queries. “If you obsess on the worst-case scenario and it happens, then it’s like it’s happened twice. So stay as positive as you can, because it might make the difference.”

https://variety.com/2018/tv/features/michael-j-fox-parkinsons-overcoming-fear-and-race-for-cure-1202898240/