Tag Archives: Central Nervous System (CNS)

The 23andMe Parkinson’s Research Study

“Somewhere, something incredible is waiting to be known.” Carl Sagan

“A dream doesn’t become reality through magic; it takes sweat, determination and hard work.” Colin Powell

Introduction/Background: Parkinson’s disease is a neurodegenerative disorder that affects movement. It evolves slowly, usually starting as either stiffness in a hand or a small tremor. Over time, Parkinson’s progresses; typically characterized by motor symptoms such as slowness of movement (bradykinesia) with rigidity, resting tremor (Parkinsonian tremor), balance and walking problems, and difficulty swallowing and talking. Parkinson’s has several non-motor symptoms including anxiety, depression, insomnia  and psychosis (just to mention a few). ~60,000 new cases of Parkinson’s disease are diagnosed each year in the United States, adding to the greater than one million people who currently have Parkinson’s.  It has been estimated that 7-10 million people worldwide are living with Parkinson’s.

“Enclose your heart in times of need with the steel of your determination and your strength. In doing this, all things will be bearable.” Lora Leigh

Genetic Testing and Introduction/Background to 23andMe:
What is the “Central Dogma of Life”? (click here) The process of how the information and instructions found in DNA to become a functional protein is termed the ‘Central Dogma’.  The concept of the central dogma was first proposed in 1958 by Francis Crick, one of the discoverers of the structure of DNA. The central dogma states that the pattern of information that occurs most frequently in our cells is as follows: (i) use existing DNA to make new DNA  (replication); (ii) next, from DNA to make new RNA (transcription); and (iii) finally, using RNA to synthesize new protein (translation). The drawing below depicts the central dogma (the drawing is from this video, click here).

23andMe: What does the name 23andMe represent? Our genetic material  (genes) are housed in chromosomes and they are composed of DNA. We have 23 pairs of chromosomes in each cell capable of producing new proteins; thus, the name of the company makes sense.  23andMe provides DNA testing services.  The information derived from studying your DNA and genetic make-up can provide information about your ancestry, your genetic predisposition to many different diseases, drug responses and inherited conditions.

“When burned on a CD, the human genome is smaller than Microsoft Office.” Steve Jurvetson

There’s an old saying that goes “Mother is always right.”:  My mother said for her entire life that we were English, Scottish (or Irish), French and German in our ancestral ‘gene pool’.  Several years ago, my extended family and I took to spitting into the 23andMe test-tubes.  We mailed them back to the company to establish our genetic history and screen our family gene pool for several diseases and their inherited susceptibility. Guess what?  Mom was absolutely right about our family ancestry.  Interestingly, there was no evidence of early onset Parkinson’s in my extended family; thus, my disorder is the sporadic/idiopathic type of Parkinson’s.

“A mother’s love for her child is like nothing else in the world. It knows no law, no pity, it dares all things and crushes down remorselessly all that stands in its path.” Agatha Christie

The 23andMe Parkinson’s research study: A few years ago, 23andMe decided to better understand the genetics of Parkinson’s disease; thus, the Parkinson’s research initiative.  Their goal is as follows: to understand the genetic associations found between Parkinson’s patients’ DNA and our disease; to take this new knowledge and search for a cure; and ultimately, they strive to enhance and speed-up how Parkinson’s disease is studied to better understand the genetics of the disease (click here to read further details) It’s easy to get involved in the 23andMe Parkinson’s research study, here are the eligibility requirements: (1) You have been diagnosed with Parkinson’s disease by a qualified physician; (2) You are willing to submit a saliva sample for DNA testing and complete online surveys related to your condition; (3) You have access to the internet; and (4) You are at least 18 years old.  The flow-chart below shows all one has to do to join this community of people-with-Parkinson’s helping out to search for a cure.
23andMe has an impressive group of  primary research partners and several other organizations as supporting partners, see below. To date, more than 10,000 people have agreed to be in 23andMe’s Parkinson’s Research Community, which makes it the world’s largest collective of genotyped Parkinson’s patients. Furthermore, many thousands of people without Parkinson’s have also consented to participate in these research studies. “Research is to see what everybody else has seen, and to think what nobody else has thought.” Albert Szent-Gyorgyi

It’s a personal decision and choice, but it’s also advancing our knowledge of Parkinson’s:  If you have concerns, look over the 3 websites cited below.  The question is should you volunteer your DNA for the study?  Should you consent to have your DNA further sequenced?  And the nice thing about being involved is you don’t have to leave your home to participate; it’s an in-house study in that they mail you the tube/device, you spit into it, and mail it back to 23andMe.  Simple. Valuable. Straightforward. Elegant.  Contributing. Joining the Parkinson’s team.

7 Things You Should Know About The Future Of Your Genetic Data (click here)
23andMe DNA Test Review: It’s Right For Me But Is It Right for You? (click here)
DNATestingChoice.com (click here for a review of 23andMe)

Ponder it, think about it some more, possibly fill out the questionnaire, upload the information, you are now part of the Parkinson’s 23andMe team. Why should you participate? You will be providing your own small piece to the Parkinson’s genetic puzzle; help complete the assembly of the landscape to this amazing puzzle.

You will matter whether you participate or not; you will always matter.  However, congratulate yourself if you decide to join the team; the 23andMe Parkinson’s research study.  You can be part of the unraveling and the delineation of the genetic anomalies that cause Parkinson’s.

“It is ironic that in the same year we celebrate the 50th anniversary of the discovery of DNA, some would have us ban certain forms of DNA medical research. Restricting medical research has very real human consequences, measured in loss of life and tremendous suffering for patients and their families.” Michael J. Fox

Cover photo credit: http://www.hdwallpapersact.com/wp-content/uploads/2013/04/ summer-sunset-on-beach-hd.jpg




Parkinson’s and the Positivity of Michael J. Fox

For everything this disease has taken, something with greater value has been given–sometimes just a marker that points me in a new direction that I might not otherwise have traveled. So, sure, it may be one step forward and two steps back, but after a time with Parkinson’s, I’ve learned that what is important is making that one step count; always looking up.” Michael J. Fox

Life-lesson plans and a living-syllabus: As a long-time educator, I feel that my daily lesson plans are partly derived from my life-experiences and that my syllabus is the sum of my life’s journey.  One view of how we live our syllabus is to see your glass either as half-full or as half-empty.  Someone with a neurodegenerative disorder like Parkinson’s might see life through a half-empty glass; however, anchoring life on a positive and hopeful tone, maybe you’d still see the glass as half-full.  When you think of Michael J. Fox and Parkinson’s, he’d definitely be a glass half-full person. Let me give some examples through his past comments.

Michael J. Fox: “We may each have our own individual Parkinson’s, but we all share one thing in common. Hope.”

Michael J. Fox and Parkinson’s: Michael J. Fox was diagnosed with Parkinson’s at the age of 29.   He has lived with his Parkinson’s for over 20 years.  He waited seven years to share the news about his diagnosis with the public.  He also quickly committed to increasing awareness of Parkinson’s research; in 2007 he founded the Michael J. Fox Foundation for Parkinson’s Research. He is widely admired for his tireless work with the Foundation and as a patient advocate for Parkinson’s.

Michael J. Fox: “In fact, Parkinson’s has made me a better person. A better husband, father and overall human being.”

Stay focused on the positive aspects of life: My own personal path to Parkinson’s (likely) started about 5-6 years ago with a firm diagnosis 2 years ago at the age of 60. My keys as I navigate life with Parkinson’s are to be positive, persistent, active (both physically and mentally), and to remain hopeful. I am a huge fan of Michael J. Fox. He remains focused on living positive with Parkinson’s, being honest about all the ups and downs associated with the disorder, and he truly believes some kind of cure is on the way.

Michael J. Fox: “My life is so filled with positives and blessings, and so filled with things I wouldn’t trade for the world.”

Practice mindfulness, take life moment by moment: Taking life as it comes, mindful to remain in the present moment is so vital to thriving (and living) with Parkinson’s.  Feeling your breath moving in and out of your lungs will help you to focus in the current time. Wake each morning and take your daily-personal-inventory. From that time on, be cognizant that you may have up-and-down interludes during the day. Try not to  worry about a future event; strive to live in the present moment.

Michael J. Fox: “Don’t imagine the worst… If you imagine the worst and it happens, you’ve lived it twice.”

Accept the diagnosis, absorb the details, live your life fully:  Accepting the diagnosis is critical because there are so many treatment strategies available; there are many  potential life-style changes possible.  Please do not resign yourself to the no-zone of care and treatment; your heart is still beating strong.  It take courage and conviction to resist the subtle changes from your disorder; you gain life-dividends from this effort.

Michael J. Fox: “Acceptance doesn’t mean resignation; it means understanding that something is what it is and that there’s got to be a way through it.”

Volunteer, serve, understand what progress is being made, own your Parkinson’s without retreating: Do what you can with what time you have. I am trying to stay upfront with research trends in Parkinson’s; I want to understand  and translate the science here in this blog. My newest task is a big reach for me because I am now part of the World Parkinson Coalition Communications Committee. As I get to know this amazing and talented team of communications experts, I will learn so much. And I truly admire their fierce devotion to all-things-Parkinson’s.

Michael J. Fox: “Medical science has proven time and again that when the resources are provided, great progress in the treatment, cure, and prevention of disease can occur.”

“Changes in Latitudes, Changes in Attitude”, assemble a good supporting team because your life-world is changing:  You can move onward without any assistance; however, bring your loved ones, family, and friends along for the journey. Have good people around you. They provide love, stability, encouragement and fuel your resilience.  Maybe with time, you might need their assistance; but for now, enjoy your life to its fullest. Manage your life and disorder, forge through it.

Michael J. Fox: “So what I say about Tracy is this: Tracy’s big challenge is not having a Parkinson’s patient for a husband. It’s having me for a husband. I happen to be a Parkinson’s patient.”

Be able to laugh and smile, even in the presence of Parkinson’s: Having Parkinson’s is a serious life-event.  However, humor can be found despite its seriousness. The 2 video clips are from “Curb Your Enthusiasm” and use humor at the expense of Michael J. Fox’s tremor and other difficulties from Parkinson’s (be prepared for ‘colorful profanity’ in their dialog).

Parkinson’s and the positivity of Michael J. Fox: For many years, Michael J. Fox has spoken honestly and openly about his Parkinson’s. His Foundation is at the forefront of funding research to help cure and/or slow the progression of this disorder. Throughout it all,  he has remained positive and hopeful during his journey.

“If you see the world and yourself through a lens smudged by negativity then you’ll find much misery. If you look outwards and inwards through lens brightened by positivity you’ll find much to be happy and appreciative about.” Henrik Edberg

“If my mind can conceive it, and my heart can believe it – then I can achieve it.” Muhammad Ali (The Soul of a Butterfly: Reflections on Life’s Journey)

Importance of Model Systems in Parkinson’s Research

“Science is organized knowledge. Wisdom is organized life.” Will Duran

“The most exciting phrase to hear in science, the one that heralds new discoveries, is not ‘Eureka!’ but ‘That’s funny…’” Isaac Asimov

Introduction:  The goal of this post is to highlight several experimental model systems that have effectively been used in Parkinson’s research.  We  have gained tremendous knowledge about all aspects of Parkinson’s from the use of model systems (Please note there are many publications that could have been included here by many different outstanding scientists; this is just a sampling of the strong science in the field of Parkinson’s disease).

The alpha-synuclein story in Parkinson’s: Alpha-synuclein is  a protein found in the brain that form aggregates (clumps of protein) called Lewy bodies.   Lewy bodies accumulate inside the substantia nigra region of the brain and they are toxic to the neurons and they no longer synthesize dopamine.   Part of the toxicity of alpha-synuclein-forming Lewy bodies is linked to mitochondria inhibition,  the little energy factories found in  our cells. This is just a sampling of alpha-synuclein in Parkinson’s (here is a PubMed search: http://www.ncbi.nlm.nih.gov/pubmed/?term=alpha-synuclein+Parkinson%27s ).

“Science is the process that takes us from confusion to understanding…” Brian Greene

The need for experimental model systems:  Scientists develop and use various experimental tools to answer their research questions. The ‘strength’ of the observation is usually dependent on the ‘quality’ of the experimental model system. Described here are four of many different experimental model systems: yeast; Caenorhabditis elegans (C. elegans); human, rat or mouse neuronal cells; and the mouse (or rat). Ultimately, scientists and physicians ‘translate’ this information for use in human clinical trials, which defines the phrase “bench-to-bedside”.


“I never guess. It is a capital mistake to theorize before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts.” Sir Arthur Conan Doyle, Author of Sherlock Holmes stories

Advancing our understanding of Parkinson’s using experimental model systems: You must remember a couple of things about science and research in general. Asking and answering one question usually leads to another question that needs to be answered. Typically, the next questions are more complex as the story unfolds. It is kind of like peeling an onion, you start taking off the top layer and you keep going; the more questions you answer the more layers you have to peel. Let’s go peel some onions.

Rising yeast in biology:  In our everyday lives,  baker’s yeast is used to make bread and alcoholic beverages like beer.  Yeast are single cell organisms, but like human cells they are eukaryotic (defined as “…cells that contain a distinct membrane-bound nucleus and by the occurrence of DNA transcription inside the nucleus and protein synthesis in the cytoplasm….” http://www.thefreedictionary.com/eukaryote ). Yeast are easy to culture and they share many similarities to human cells;  furthermore, genetic manipulation is relatively easy to do in yeast and offers a powerful tool for biomedical science. [Also see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213361/%5D

Use of yeast in Parkinson’s research Tardiff and others performed a really clever experiment, they expressed alpha-synuclein in yeast.  They found that yeast, just like human neuronal cells, got sick in the presence of excess amounts of alpha-synuclein.  They used the yeast expressing alpha-synuclein  and asked the following questions. Could a compound neutralize or reverse the alpha-synuclein-induced toxicity in yeast? Would this compound be able to restore normal function to the yeast?  They tested  ~190,000 compounds to see whether any of those would reverse the toxic effects and allow the yeast to rapidly grow again.  One lead compound evolved from this study, N-aryl benzimidazole (NAB).  NAB corrected the problem in yeast expressing alpha-synuclein. Using elegant genetics, they found that NAB activates a “trafficking” protein named Rsp5. The alpha-synuclein-induced toxicity  was inhibiting the function of Rsp5, which means that NAB reverses this effect. This sets the scene for new pathways to be explored for how Parkinson’s evolves, and presents a new strategy for exploring drugs to treat this disorder.
Tardiff DF, Jui NT, Khurana V, et al. Yeast reveal a “druggable” Rsp5/Nedd4 Network that Ameliorates α–Synuclein Toxicity in Neurons. Science (New York, NY). 2013;342(6161):979-983. doi:10.1126/science.1245321.

“Science is a way of thinking much more than it is a body of knowledge.” Carl Sagan

“Worm people” advancing science using C. elegans: C. elegans are non-parasitic soil nematodes that are free-living (…worms of the phylum Nematoda, having unsegmented cylindrical bodies often narrowing at each end, and including free-living species that are abundant in soil and water, and species that are parasites of plants and animals…” http://www.thefreedictionary.com/nematode ). C. elegans is a model organism due to its ability to be easily grown and manipulated genetically, which scientists use to advance complex biological principles.  [Also see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855192/%5D

Use of worms in Parkinson’s research Advanced age is the greatest known risk factor for development of Parkinson’s.  Why this happens is not fully understood. Cooper and others proposed the following hypothesis: “…there are specific changes that take place during the aging process that make cells susceptible to disease-causing mutations that are well-tolerated at younger ages.” To begin to ‘test’ this hypothesis, they used genetics and C. elegans as a model system.  Worms containing mutations in the daf-2 gene live twice as long as control worms.  The researchers crossed  C. elegans models of Parkinson’s with daf-2 mutants.  Compared to the appropriate control worms, the Parkinson’s/daf-2 mutant worms had longer lifespan, protection of dopamine neurons, resistance to inflammatory stress, and decreased Lewy-body formation. This C. elegans genetics-aging study implies that slowing down the aging process is neuroprotective in Parkinson’s.
Jason F Cooper, Dylan J Dues, Katie K Spielbauer, Emily Machiela, Megan M Senchuk, and Jeremy M Van Raamsdonk. Delaying aging is neuroprotective in Parkinson’s disease: a genetic analysis in C. elegans models. npj Parkinson’s Disease (2015) 1, 15022; doi:10.1038/npjparkd.2015.22; published online 19 November 2015

“What we find changes who we become.” Peter Morville

Cells provide a cultivating environment to model tissues/organs:  Over the past several decades, many different types of cells have been grown in sterile plastic dishes; ranging from “primary” cell extracts obtained from different organs to “immortalized” cell types from various tumor types (i.e., cancer).  Cells grown in vitro (defined as “performed or taking place in a test tube, culture dish, or elsewhere outside a living organism” https://www.google.com/search?q=define+in+vitro&ie=utf-8&oe=utf-8) do not fully recapitulate the organ of origin; nonetheless, cell culture is a powerful model system to study both normal biological and abnormal pathological processes. [Also see http://www.biologyreference.com/Bl-Ce/Cell-Culture.html%5D

Use of neuronal cells in Parkinson’s research Proteins have unique three-dimensional shapes, which encode their biological activity.  Sometimes, proteins go bad and do things that are pathological like alpha-synuclein forming aggregates. Moree and others are testing a hypothesis that small molecules can be discovered that reverse such detrimental protein aggregation. They developed a novel screening technique to identify compounds that modulate protein conformation (which is way beyond the scope of this blog posting). They discovered a compound named BIOD303 as a novel conformational modulator of alpha-synuclein.Interestingly, these modulators reduced alpha-synuclein aggregation in an experimental neuronal cell model. This sort of study could (possibly one day) lead to a novel process for treating Parkinson’s by reversing alpha-synuclein aggregates.
Moree B, Yin G, Lázaro DF, et al. Small Molecules Detected by Second-Harmonic Generation Modulate the Conformation of Monomeric α-Synuclein and Reduce Its Aggregation in Cells. The Journal of Biological Chemistry. 2015;290(46):27582-27593. doi:10.1074/jbc.M114.636027.

“Science does not know its debt to imagination.” Ralph Waldo Emerson

The mouse (rat) provides a most important model system:  Our understanding of many human diseases (think cardiovascular, cancer, and yes, Parkinson’s) has been advanced using mice and rats as model systems. One reason why mice are used is the similarity of mouse and human genetics. Scientists have done amazing feats using mice including “gene knockout” where specific genes have been deleted or inactivated.  Another type of mouse genetically-derived is the “transgenic mice”, which usually express genes thought to promote human diseases.  Ultimately, a mouse (or rat) with a specific disease becomes a model or ‘stand-in’ for that same human disease or condition.  [Also see  http://emice.nci.nih.gov/aam%5D

Use of rats in Parkinson’s researchVolakakis and others studied how alpha-synuclein promotes changes in dopamine-producing neurons. They found that alpha-synuclein alters gene expression and that a transcription factor (a protein that binds to specific DNA sequences that modulates the genetic information being transcribed from DNA to messenger RNA) known as Nurr1 helps resist these effects. They found that nuclear substances that bind to Nurr1’s partner retinoid X receptor (RXR) also had a neuroprotective role. Their results clearly highlight Nurr1’s neuroprotective role against alpha-synuclein-induced changes in dopamine-producing neurons. Furthermore, their results imply that RXR ligands have therapeutic potential in Parkinson’s.
Volakakis N, Tiklova K, Decressac M, Papathanou M, Mattsson B, Gillberg L, Nobre A, Björklund A, Perlmann T. Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression. J Neurosci. 2015 Oct 21;35(42):14370-85. doi: 10.1523/JNEUROSCI.1155-15.2015. PMID:26490873

“Barry L. Jacobs and colleagues from the neuroscience program at Princeton University showed that when mice ran every day on an exercise wheel, they developed more brain cells and they learned faster than sedentary controls. I believe in mice.”  Bernd Heinrich

From bench-to-bedside: The four papers described here represent the tip-of-the-iceberg in Parkinson’s research. As with any basic science study, the next step, the next few years are key to developing/advancing/evaluating these questions and getting answers. I am optimistic that new compounds, new treatment strategies, and further understanding of Parkinson’s are coming in the near future. It just will take time, so we must remain patient while all of their research endeavors progress.

“From the standpoint of daily life, however, there is one thing we do know: that we are here for the sake of each other – above all for those upon whose smile and well-being our own happiness depends, and also for the countless unknown souls with whose fate we are connected by a bond of sympathy. Many times a day I realize how much my own outer and inner life is built upon the labors of my fellow men, both living and dead, and how earnestly I must exert myself in order to give in return as much as I have received.” Albert Einstein

Cover photo credit: http://www.boredpanda.com/beautiful-winter-photos/


Neuroprotection by Modified-Macrophages in a Parkinson’s Model System

“Somewhere, something incredible is waiting to be known.” Carl Sagan

“You never change things by fighting the existing reality.  To change something, build a new model that makes the existing model obsolete.” R. Buckminster Fuller

Précis: Scientists at the University of North Carolina at Chapel Hill are using an innovative approach to treat Parkinson’s in a model animal system (I realize this is my University, but it’s still very cool science). Dr. Elena Batrakova’s research is focused on engineering macrophages (a key host defense cell) for delivery to and therapy in the brain.  This “Trojan Horse” therapeutic system has been used for treating Parkinson’s in an animal model (go here: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106867).

What is a Trojan Horse therapeutic system?  From Greek mythology:The Trojan Horse is a tale from the Trojan War about the subterfuge that the Greeks used to enter the city of Troy and win the war. In the canonical version, after a fruitless 10-year siege, the Greeks constructed a huge wooden horse, and hid a select force of men inside.” (https://en.wikipedia.org/wiki/Trojan_Horse).  From  modern neuroscience and molecular engineering: The Trojan Horse therapeutic system is to use a naturally occurring cell (macrophage) that fools the body (to get into and past the blood brain barrier) into accepting the cell as self. After being accepted as self, it allows the material housed inside the macrophage to be released directly at the site of injury (mid-brain region called substantia nigra that has dopamine producing cells). The drawing below illustrates the science of this study and the depiction of the Trojan Horse.


“Everything is theoretically impossible, until it is done.” Robert A. Heinlein

What are macrophages (in this study they are the Trojan horse)? Bone marrow makes many different cell types including red blood cells, white blood cells (WBC), and platelets. Macrophages are derived from the WBC named monocyte. Monocytes released from the bone marrow circulate in the bloodstream for a couple of days and leave and go to the various organs and tissues where they mature and become macrophages.  Macrophages are incredibly versatile and important cells in our host defense system; including a role as a sentinel, a role as a  General in a bunker giving out orders to all the other soldiers, and even a role functioning as a garbage collector. Let me explain. Macrophages live in our tissues and they stand guard ready to attack invading microorganisms.  Macrophages generate many different substances (growth factors and  cytokines)  that recruit and activate WBC’s both to enhance the attack against invading microorganisms  and to initiate the immune system.  Macrophages also help out by cleanup debris and cellular waste products. Macrophages can be activated when  exposed to different kinds of inflammatory cytokines and they become what are called M1 and M2 macrophages.  M1 macrophages have a role being pro-inflammatory while M2 macrophages have a role being regenerative.

“The good thing about science is that it’s true whether or not you believe in it.” Neil deGrasse Tyson

What is GDNF (in this study it is the Greek soldiers)? GDNF  stands for glial cell-line derived neurotrophic factor  (neurotrophic substances regulate the growth, survival, and differentiation of nerve cells/nervous tissue).  There is evidence in the scientific literature of the positive impact of neurotrophic factors in experimental treatment of Parkinson’s. The idea behind using GDNF is to promote survival of dopamine producing neurons and also to reduce inflammation in the mid-brain area. One of the major obstacles to this research area in general has been delivering the neurotrophic factor through the blood brain barrier and to the damaged tissue. The study here gets around this by using the macrophage as the carrier to deliver GDNF, the neurotrophic factor, directly to the brain.

“Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less.” Marie Curie

Is this research similar to regenerative medicine?  Ultimately, if this science translates from bench-to-bedside, it satisfies elements of what is called regenerative medicine.  By definition, “regenerative medicine is a branch of translational research in tissue engineering and molecular biology which deals with the ‘process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function.'” (https://www.google.com/search?q=personalized+medicine&ie=utf-8&oe=utf-8#q=regenerative+medicine+definition).  The approach used in this study was first, to use the macrophage as the protective cell carrier and as the decoy in the Trojan horse model. And second, to express GDNF in the macrophage and have the macrophages deliver the neurotrophic factor directly to the brain. This idea is partially based on the hypothesis that macrophages would migrate toward areas of inflammation; there is substantial evidence linking inflammation in the mid-brain region to someone with Parkinson’s.

“Wonder is the seed of knowledge” Francis Bacon

 Was there good news using GDNF-expressing macrophages in the experimental mouse model of Parkinson’s?   There were several notable positive results from the study, including: 1)  macrophages were able to be transfected with GDNF; 2)  macrophages were activated to the M2 regenerative state; 3) injecting GDNF-expressing macrophages into the Parkinson’s disease mouse showed significant  improvement in both neuroinflammation and  neurodegeneration; 4) behavioral studies confirmed the neuroprotective effect in the mouse model; and 5) these results indicate successful   delivery of GDNF by macrophages, release of GDNF into the affected area, and transfer of the neurotrophic factor to the appropriate targeted neurons.

“The scientist is not a person who gives the right answers, he’s one who asks the right questions.” Claude Lévi-Strauss

Of ‘Mice and Men’, what do the results mean for the future treatment of Parkinson’s?  The results of this paper are both elegant and straightforward.  Their overall goal is to use cell-mediated delivery of therapeutic substances that either stop or slow progression of Parkinson’s. Doing this successfully in a mouse model is one thing; however, getting it translated into a human study is another. We must remain positive that scientists of this caliber continue to get their research funded, continue to train scientists in the neurodegenerative field, and continue to publish their results.  We must remain persistent in managing our own disorder because there are several important studies going on right now; and some of them could reverse and/or slow down the progression of Parkinson’s.  Is this really possible? Time will tell whether this study translates from mice to men.  Finally, I am hopeful that in the near-future a strategy will emerge to slow/halt the progression of Parkinson’s; allowing our return to normalcy.

“The important thing is to not stop questioning. Curiosity has its own reason for existence. One cannot help but be in awe when he contemplates the mysteries of eternity, of life, of the marvelous structure of reality. It is enough if one tries merely to comprehend a little of this mystery each day. Albert Einstein —”Old Man’s Advice to Youth: ‘Never Lose a Holy Curiosity.'” LIFE Magazine (2 May 1955) p. 64”


Potential New Parkinson’s Drug Highlight: the Leukemia Drug Nilotinib

“With Parkinson’s you have two choices: You can let it control you, or you can control it. And I’ve chosen to control it.” US Senator Isakson

“Learn from yesterday, live for today, hope for tomorrow. The important thing is to not stop questioning.” Albert Einstein

Introduction: In my academic career to-date, my research group and I have presented over 170 abstracts at international science, medical and education meetings.  These abstracts have been poster presentations, short-program talks or invited plenary session presentations (to view a sample of my research group presentations, click here:Church.Frank_SelectedAbstracts.2015).  Abstracts represent the best science from research laboratories; they are like invitations to look over what we study science-wise.

Presenting abstracts could  result in a news organization describing it to the public.  At the recent Neuroscience 2015 meeting, the following abstract was presented (click here to read it: Abstract.GeorgetownStudy): “Nilotinib significantly alters blood and CSF α-Synuclein and p-Tau levels, inhibits dopamine breakdown and increases neuro-restorative markers in an open-labelled Parkinson’s disease with dementia and Lewy body dementia trial.”  Over the past few weeks (Google search “Leukemia drug and Parkinson’s” or “Nilotinib and Parkinson’s”), several news and science organizations have written about this study with much fanfare and with necessary reservations.  Below are my observations on the science of Nilotinib [Pronunciation: nye LOE ti nib (Brand Name: Tasigna)] for treating Parkinson’s; hopeful for its potential combined with concerns.

“Not many appreciate the ultimate power and potential usefulness of basic knowledge accumulated by obscure, unseen investigators who, in a lifetime of intensive study, may never see any practical use for their findings but who go on seeking answers to the unknown without thought of financial or practical gain.” Eugenie Clark

Science of Gleevec and Nilotinib in treating chronic myelocytic leukemia (CML), the “Philadelphia Story”:  CML is a leukemia (blood cancer) from a deranged bone marrow stem cell, the progeny expand to displace all normal bone marrow. CML is characterized by the presence of the Philadelphia chromosome (Ph) in the leukemic cells. Clonal expansion leads to deranged overproduction of white blood cells by subordinate cell lines. Each year in the USA, there are ~5800 new CML cases with ~600 deaths; CML accounts for ~10% of all new cases of leukemia.

The Philadelphia chromosome (Ph) was first described in 1960; yes, it was discovered in Philadelphia. The Ph chromosome is a reciprocal translocation involving chromosomes 9 and 22: t(9;22) (q34;q11) [cutting and pasting together chromosomes, not a good thing to happen]. The chromosomal rearrangement of Ph brings two cell-signaling substances together (they are named Bcr and Abl); the fused-chimeric Bcr-Abl gene has “unnregulated” tyrosine kinase activity. Bcr-Abl is necessary and sufficient to cause CML. This fusion Bcr-Abl interacts with many signaling pathways and it keeps the cell proliferation (growth) machinery on and cell differentiation (maturation) machinery off.   The action of Bcr-Abl would be like having both feet on the car’s accelerator (go-go-go) with no control of the brakes. Ultimately, the result of the Bcr-Abl fusion is to speed up cell division.

Imatinib (Gleevec) was found to be a novel and potent inhibitor of Bcr-Abl. Gleevec inhibits growth of Bcr-Abl positive cancer cells; it is orally bioavailable and well tolerated by most CML patients. Gleevec was the first drug of its kind used for directed-chemotherapy. Nilotinib is a second-generation Bcr-Abl inhibitor used to treat CML; including those people whose disease could not be treated successfully with Gleevec or people who cannot take Gleevec.

“It would be possible to describe everything scientifically, but it would make no sense; it would be without meaning, as if you described a Beethoven symphony as a variation of wave pressure.” Albert Einstein

Science of Nilotinib in treating Parkinson’s: The cell signaling protein c-Abl (tyrosine kinase) is involved in numerous cellular processes. Its cancer-related fusion counterpart, Bcr–Abl protein, promotes leukemia. In 2010, Johns Hopkins scientists reported that c-Abl was up-regulated in Parkinson’s; which led to a build-up of denatured proteins that promoted neuronal cell death and the progression of Parkinson’s (http://www.ncbi.nlm.nih.gov/pubmed/20823226).

Here is a plausible pathway for the development of Parkinson’s and the use of CML (Bcr-Abl) inhibitors to treat this disorder:
1. Parkinson’s develops from a loss of dopamine-producing brain cells.
2. These cells accumulate a protein named alpha (α)-synuclein that aggregates in the cell, which stresses and ultimately leads to death of the cell.
3. The physiological process responsible for clearing out this cellular debris is known as autophagy (see schematic below for an overview of autophagy).
4. A protein named parkin protects brain cells by enabling autophagy, (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592826/). The action of autophagy is kind of analogous to the garbage disposal in your kitchen sink.
5. c-Abl ‘labels’ parkin and this modification  inhibits parkin function.
6. c-Abl up-regulation in Parkinson’s would leads to parkin dysfunction; Without autophagy activation, toxic parkin substrates (AIMP2 and FBP1) and denatured forms of α-synuclein accumulate and the dopamine-synthesizing cell dies.
7. This implies that inhibition of c-Abl could be neuroprotective.
8. To recap: over-activation of c-Abl prevents parkin from promoting autophagy, allowing for a build-up of toxic substances that can kill brain cells to begin the progression of Parkinson’s.
9.Two newer studies using animal models of Parkinson’s showed that brain-penetrating c-Abl inhibitors were neuroprotective (see http://www.ncbi.nlm.nih.gov/pubmed/23741470 and http://www.ncbi.nlm.nih.gov/pubmed/24786396 ).


“All trials are not the reason to give up, but a challenge to improve ourselves. Our pain is not an excuse to back out, but an inspiration to move on.” Anonymous/unknown

Nilotinib may be a molecular Drāno in treating Parkinson’s:  With this background story, let’s visit the Georgetown abstract/results. Dr. Charbel Moussa and Dr. Fernando Pagan led the pre-clinical research study. Reminder: Nilotinib is a second-generation Bcr-Abl inhibitor used to treat the blood cancer CML.  Thus, their initial goal was to test the safety of Nilotinib in treating patients with Parkinson’s and Lewy body dementia.  If Nilotinib was safe and well-tolerated, a second goal was to measure motor skills and cognitive function. This was a small phase I clinical trial with 11-12 patients receiving Nilotinib for 6 months (150-300 mg/day).

Why was there so much excitement in this preliminary drug study? Because treatment with Nilotinib actually improved and, in some patients, reversed impaired motor skills, non-motor functions, and cognitive functions  in Parkinson’s and Lewy body dementia patients. Some of the more remarkable changes from 6 months of treatment with Nilotinib included three individuals unable to speak before could now hold conversations, and one individual previously confined to a wheelchair could now walk again.

Nilotinib was used at a lower dose (150-300 mg/day) then recommended for treating CML (800 mg/day).  The higher dose would promote cell death during treatment of Bcr-Abl-positive CML cells. By contrast, the lower dose would inhibit (not kill) c-Abl-positive neuronal cells. They hypothesize that the lower dose initiates  autophagy to remove toxic proteins in the absence of cell death. It would be analogous to Nilotinib being a molecular Drāno.  In household use,  you pour Drāno into a clogged drain, wait a few hours, wash with hot water, and the result is an unclogged drain.


There were several issues with this study that all have noted.  Besides being a very small clinical trial, limitations were as follows:  lack of a control group for comparison, and Nilotinib was not compared to a placebo or any existing Parkinson’s drugs. We must also remember the primary goal of this study was that of a Phase I Clinical trial.  “Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.” (https://www.nlm.nih.gov/services/ctphases.html )

“Getting diagnosed has made me want to grab life and squeeze every last ounce of fun and opportunity from it.” Emma Lawton

Closing comments from a scientist with Parkinson’s: This study using the cancer drug Nilotinib to treat individuals with Parkinson’s and Lewy body dementia both excites me and worries me.  First, the results were very preliminary; let’s see how the planned 2016 studies turn out (this time with controls). Second, there are potential adverse side effects of Nilotinib (http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm218929.htm), which when added to the side effects of the existing arsenal of Parkinson’s therapies, it could be somewhat problematic. Third, Novartis claims the cost of Nilotinib for CML chemotherapy (800 mg/day) is  ~$10,000/month. While the dose used in this study was less (150 and 300 mg/day), off-label use and cost could be problematic for many individuals.  Fourth,  the idea of re-engaging autophagy to clear out toxic substances to rejuvenate the neuron is intriguing; however, much basic science is needed to validate this hypothesis.

Finally, if there was ever a “good time” to have Parkinson’s, it may be now. We have taken giant strides in our understanding of the pathophysiology of Parkinson’s.  There are numerous clinical trials currently underway testing novel therapies.  I can’t wait to read these innovative biomedical and clinical trial abstracts in 2016-2017. We must remain hopeful that we are on the cusp of several new treatment strategies to halt the progression of Parkinson’s.

 “With the support of my family and friends, I will meet this challenge with the same determination and unwavering intensity that I have displayed in all of my endeavors in life.” Kirk Gibson

A few examples of other reports:

Science of Advanced Age as a Risk Factor for Parkinson’s

“Spring passes and one remembers one’s innocence.
Summer passes and one remembers one’s exuberance.
Autumn passes and one remembers one’s reverence.
Winter passes and one remembers one’s perseverance.”
Yoko Ono

“Embrace aging.” Mitch Albom, Tuesdays with Morrie

Précis: The great majority of individuals with Parkinson’s reveal no genetic mutations, no past history of head injury, no prior exposure to pesticides/toxins, or any family history of the disorder.  Public health studies have consistently shown that advanced age is an adverse risk factor for developing Parkinson’s. The average age of Parkinson’s onset is ~60 years of age. Presented here is a brief overview about why advanced age is a major risk factor for Parkinson’s.

Parkinson’s and advanced age as a risk factor: Parkinson’s is a neurodegenerative disorder that affects movement. It starts slowly, usually a small tremor or stiffness in a hand. With time, Parkinson’s progresses; typically characterized by motor symptoms such as slowness of movement (bradykinesia) with rigidity, resting tremor (Parkinsonian tremor), balance and walking problems, and difficulty swallowing and talking. Parkinson’s has several non-motor symptoms including anxiety, depression, and insomnia (just to mention a few).

Following Alzheimer’s, Parkinson’s is the second most common neurodegenerative disorder affecting ~0.3% of the developed world population. Interestingly, the incidence of Parkinson’s increases to 3% for persons >65 years old, which strongly indicates that advanced age is a major risk factor for this disorder.

Aging can promote several detrimental events that damage the dopamine-producing neurons in the substantia nigra.  These pathological events accumulate and weakens the ability of these neurons to respond to further insults, which ultimately leads to Parkinson’s (see below).

The left-side of the composite picture below could be entitled “40 years of Frank (in my 20’s, 30’s, 50’s and 60’s).”  The title of the right-side of the composite picture could be “Somehow the neurons in my substantia nigra (top right) are making very little dopamine (chemical structure bottom right); thus, I have Parkinson’s.”

Frank+40yrs“As long as I am breathing, in my eyes, I am just beginning.” Criss Jami

Age of the U.S. population: Andy Rooney once said “It’s paradoxical that the idea of living a long life appeals to everyone, but the idea of getting old doesn’t appeal to anyone.”  As the table below shows, by each successive decade of life, females outlive males. However, between 2000 and 2010, the U.S. male population grew at a slightly faster rate than the female population. By contrast, mortality rates in older men differ from older women, where the census results showed that women tend to live longer than men.  A further breakdown shows the 65 to 69 year old age group grew by 30%; this age group represents the leading edge of the Baby Boomers who started turning 65 in 2011 (The Baby Boom includes people born from mid-1946 to 1964). We are living longer; when coupled with advanced age as a risk factor for Parkinson’s, this implies an increasing burden on health care systems to deal with this disorder.

“Wisdom comes with winters.” Oscar Wilde

Science behind advanced age as an adverse risk factor for Parkinson’s:  Pat Benatar said this about aging, “I’ve enjoyed every age I’ve been, and each has had its own individual merit. Every laugh line, every scar, is a badge I wear to show I’ve been present, the inner rings of my personal tree trunk that I display proudly for all to see. Nowadays, I don’t want a “perfect” face and body; I want to wear the life I’ve lived.”  Advanced age contributes to many different diseases whether from a loss of organ function with time, diminished immune surveillance capacity, or the inability to remove naturally-accumulating toxic substances by the host defense mechanisms (just to describe a few of many possible outcomes of advancing age).

In evaluating a large group of elderly people without Parkinson’s (750 individuals with an average age of 88.5 years), it was noted that ~1/3 showed mild to severe substantia nigra neuronal cell loss. Thus, natural advanced aging results in some loss to the dopamine-producing substantia nigra mid-brain region. But what shifts the balance that leads to Parkinson’s in some individuals?  Reeve et al. (2014), in an outstanding article, reviewed the science behind why advancing age is the biggest risk factor for Parkinson’s.  They suggest three processes occur in the substantia nigra that ultimately leads to Parkinson’s: (1) detrimental changes to the microenvironment; (2) dysfunction of the subcellular organelles called mitochondria; and (3) disruption in the process of protein degradation (the drawing below highlights these processes).

Aging.SN(1) Detrimental changes to the substantia nigra microenvironment:  As an analogy, over time, with extended use and re-use, your laptop slows down and ultimately begins little processor-derived-hiccups-of-dysfunction.  As we age, some changes occur in the dopamine-producing neurons of the substantia nigra; these include increased oxidative stress, changes in calcium-neuron properties, modification of iron-neuron interactions, and accumulation of the pigment called neuromelanin.  Processing of dopamine in the substantia nigra generates detrimental oxidative stress; which is made worse due to an age-related reduction of a protein named the dopamine transporter (DAT). The DAT escorts dopamine from neuron-to-neuron to reduce oxidative stress. Calcium helps maintain dopamine levels; and sustained transport of calcium into the cell is detrimental to the energy-producing organelle, the mitochondria.  Iron is an essential element; however with age, iron accumulates to contribute to the oxidative stress. Neuromelanin is responsible for the color of the substantia nigra.  Evidently, neuromelanin accumulates with age; in contrast to the other factors mentioned above, neuromelanin may be neuroprotective.

(2) Dysfunction of the subcellular organelles called mitochondria:  As an analogy, over time, you charge the battery of many devices like your cell phone, laptop/tablet, toothbrush, and beard trimmer; eventually no matter what you do, slowly but surely these devices lose their charge.  Likewise, mitochondria are subcellular power factories that can become dysfunctional (and lose energy) with advancing age. The mitochondrial respiratory system (electron transport) is a major cellular energy producer; and it consists of five protein complexes named respiratory complexes I–V. Several mitochondria electron transport complexes are modified/inhibited with age, leading to a loss of mitochondria-derived energy. Inhibiting complex I (reduced NADH dehydrogenase–ubiquinone oxidoreductase) causes Parkinsonian-like symptoms; furthermore loss of complex IV (cytochrome c oxidase) promotes a respiratory deficiency. This leads to the reduction of energy production (ATP molecules), which would negatively impact “neuronal excitability” (engaging/activating the neuron). Linked to this energy drain is mutation of mitochondria DNA, causing further detriment to these dopamine-producing neurons. These mutations ultimately reduce mitochondria function and activity, which promotes the accumulation of mis-folded proteins (a very bad thing). A key disease-causing feature of Parkinson’s is the build-up and denaturation of the protein named alpha-synuclein (think of the changes of frying an egg, which goes from clear to cloudy-opaque as the heat cooks and denatures the egg proteins). Accumulation of alpha-synuclein protein aggregates advances further mitochondria impairment.

(3) Disruption in the process of protein degradation:  As an analogy, shaving with a new razor blade leads to complete cutting-off of the hair; however, over time, as the razor blade dulls you end-up with more and more uncut hair. Similarly, we use enzymes called proteases and they are somewhat like a razor blade; their goal is to cut-up (digest) proteins.  Proteases are used in many different biological settings (e.g., digestion of food, clotting of blood); in the substantia nigra, proteases help eliminate protein debris as a means of self-renewal of the neurons.  There are two types of protease processes that cut and remove accumulating damaged proteins (like alpha-synuclein aggregates); they are named the ubiquitin proteasome system and autophagy.  Due to their complex biology, neither the ubiquitin proteasome system nor autophagy will be further described here; suffice it to say that if both protease systems are diminished this will further impair mitochondria.  These checks-and-balances are lost with advanced aging, which leads to a concert of adverse events where an individual could develop Parkinson’s.

“There is a fountain of youth: it is your mind, your talents, the creativity you bring to your life and the lives of people you love. When you learn to tap this source, you will truly have defeated age.” Sophia Loren

A symphony combining (1) + (2) + (3) from above + advancing age = risk of developing Parkinson’s: The natural-biology of dopamine-producing neurons leads to declining function with advanced aging. The detrimental process of reactive oxygen species initiates a symphony of badness that leads to neuronal cell dysfunction/death. The larghetto first movement leads to the reduction of the DAT, accumulation of neuromelanin, increased iron deposits, and disruption of calcium transport. The next movement is fortissimo with mutation of mitochondria DNA, inhibition of complex I and complex IV to reduce both ATP levels and neuronal excitability; these events lead to the acquisition of other mitochondria defects. The cadenza results in the beginning phase of aggregating alpha-synuclein, which contributes to substantia nigra dysfunction.  In the final movement of our symphony, we reach a crescendo where toxic levels of aggregating alpha-synuclein accumulate that cannot be cut/removed by the protein degradation pathways. The symphony ends with substantial stress to the dopamine-producing neurons in the substantia nigra to eventually promote neuronal cell death, which results in Parkinson’s.  With advancing age, most individuals will stop at the end of the first movement (microenvironment changes to substantia nigra); while others will complete the entire symphony over-and-over again to develop Parkinson’s.

“Age has no reality except in the physical world. The essence of a human being is resistant to the passage of time. Our inner lives are eternal, which is to say that our spirits remain as youthful and vigorous as when we were in full bloom. Think of love as a state of grace, not the means to anything, but the alpha and omega. An end in itself.” Gabriel García Márquez, Love in the Time of Cholera

References Cited:
Reeve, A., et al, Ageing and Parkinson’s disease: Why is advancing age the biggest risk factor?, Ageing Research Reviews, Volume 14, March 2014, Pages 19-30, http://dx.doi.org/10.1016/j.arr.2014.01.004.

Abdullah, R., et al., Parkinson’s disease and age: The obvious but largely unexplored link, Experimental Gerontology, Volume 68, August 2015, Pages 33-38, http://dx.doi.org/10.1016/j.exger.2014.09.014.

Petralia, R.S. , et al., Communication breakdown: The impact of ageing on synapse structure, Ageing Research Reviews, Volume 14, March 2014, Pages 31-42, http://dx.doi.org/10.1016/j.arr.2014.01.003.

Mhyre, Timothy R. et al. Parkinson’s Disease. Sub-cellular biochemistry 65 (2012): 389–455. PMC. Web. 9 Nov. 2015.  doi:  10.1007/978-94-007-5416-4_16  PMCID: PMC4372387

Poetry to Parkinson’s

“The greatest wisdom is in simplicity. Love, respect, tolerance, sharing, gratitude, forgiveness. It’s not complex or elaborate. The real knowledge is free. It’s encoded in your DNA. All you need is within you. Great teachers have said that from the beginning. Find your heart, and you will find your way.” Carlos Barrios, Mayan elder and Ajq’ij of the Eagle Clan

Defining Parkinson’s disease: Parkinson’s start from the loss of dopamine-producing neurons in the substantia nigra region of the brain.  Lewy bodies are found in these cells; they are denatured aggregates of the protein named alpha-synuclein. Formation of Lewy bodies promote neuronal cell dysfunction and death. Parkinson’s presents mostly as a movement disorder (rigidity, slowness of movement, postural instability, and resting tremor).

Defining poetry and a poet: Jane Kenyon said “The poet’s job is to put into words those feelings we all have that are so deep, so important, and yet so difficult to name, to tell the truth in such a beautiful way, that people cannot live without it.”  Likewise, Robert Frost remarked “There are three things, after all, that a poem must reach: the eye, the ear, and what we may call the heart or the mind. It is most important of all to reach the heart of the read.”

TED talks and a poet with Parkinson’s: Most people have heard of TED talks. TED (Technology, Entertainment, Design) conferences follow the slogan of “Ideas Worth Spreading”.  Many  universities and organizations have TEDx meetings (e.g., TEDxUNC), which are both fun and inspiring to attend.  The primary reason for writing this particular blog is to connect you with Robin Morgan’s TED talk. Robin is a poet with Parkinson’s.  Her poems she presented at a recent TED conference are beautiful and moving.  I can definitely agree with much of her description of Parkinson’s. Clearly, it is a well-deserved honor to be chosen to present at a TED meeting.

TED talk:

Difference between prose and poetry, and prose to Parkinson’s:  Maeve Maddox writes “What makes a poem ‘good’? The answer ultimately lies with the reader of the poem, but there is a certain consensus as to what makes a poem ‘good’ or ‘bad.’ According to the critic Coleridge, prose is ‘words in their best order,’ while poetry is ‘the best words in their best order.’ Poetry demands precision…The job of the poet is to create a picture in the mind and an emotion in the heart. Every single word counts.”  [go here for the complete article: http://www.dailywritingtips.com/telling-a-good-poem-from-a-bad-one/ ]. Based on this description, I am clearly not a poet.  However, here’s an attempt at prose to Parkinson’s.

Live on, life has not yet been cancelled
Living with Parkinson’s is like walking on the beach as high-tide approaches; sand moving under your feet while the water hits your ankles that brings some imbalance to your movement.  As high tide continues in, walking becomes even more difficult. Likewise, with Parkinson’s you handle the difficulty, adapt to the changes, manage the progression, and live on.

Living with Parkinson’s says your future life will be different from your life before.  Accept the diagnosis, do not let it define you, challenge it, continue to thrive and be happy, and live on.

Living with Parkinson’s says subtle progression is expected. Stay active, keep exercising, be mindful, remain persistent, be positive, show gratitude, and live on.

Living with Parkinson’s today says there is still no cure.  We must remain hopeful and stay educated because advances are being reported weekly for neurodegenerative disorders.  Small steps to better understanding brings us closer to new therapies, slowing progression and more, please live on.

Living with Parkinson’s says you are still you today.  The same you from before the diagnosis. Stay active, be focused and, as always, remain hopeful. Live on, life has not yet been cancelled.

Day-by-day with Parkinson’s
Daily life after the diagnosis, I feel the following
Physically; a little different but getting stronger.
Inner-self; mindfulness matters.
Intellectually; focused, very focused on learning more.
Emotionally; stable but brittle, determined to expand.
Psychologically; seeking to understand.
Outreach; ready to help others understand Parkinson’s.
Consciously; ready, awake, hungry, capable.
Educationally; able, capable, ready to expand.
Mood; happy, want some red wine.
Motivation; ready, really ready to understand the brain.
Sleep; too many sleepless work-filled nights, sleepy.
Future; the big unknown, focus on the moment, breathe.

Dopamine, my constant symbol of hope
The molecular formula of dopamine is C8H11NO2. In terms of chemical structure it’s relatively simple; however, in terms of functional value it’s the missing ingredient to my disorder, to the one named Parkinson’s. My new life-pattern can be blamed on the reduced synthesis of dopamine. The result is my newfound reliance for a dopamine agonist; a complex chemical to mimic my simple dopamine.

Dopamine is more than just a neurotransmitter; it is truly my symbol of hope and renewed possibilities. C8H11NO2 solves my new life’s-riddle and confounding mysteries. This allows me to learn a lot about Parkinson’s science; which further gives me opportunity to educate others. And remember Mark Watney’s words (Matt Damon in “The Martian”): “I’m going to have to science the shit out of this.” The key, to never lose hope and to remain persistent, optimistic, and informed.

IMG_7656“It did not really matter what we expected from life, but rather what life expected from us. We needed to stop asking about the meaning of life, and instead to think of ourselves as those who were being questioned by life—daily and hourly. Our answer must consist, not in talk and meditation, but in right action and in right conduct. Life ultimately means taking the responsibility to find the right answer to its problems and to fulfill the tasks which it constantly sets for each individual.”  Viktor Frankl