New Year’s Resolutions

Laura’s pinup – Michael J. Fox

Do you have a New Year’s resolution to volunteer more?  Or to help cure Parkinson’s?  Here’s an easy way to fulfill both of those resolutions: Sign up for Fox Trial Finder and Fox Insight.

These are two different projects of Michael J. Fox Foundation (MJFF):
–Fox Trial Finder:  A database of potential volunteers for Parkinson’s research.
–Fox Insight:  A quarterly survey of Parkies’ experience with the disease.

I am a big fan of MJFF – ya gotta love any charity that wants to go out of business.  They recently adopted a new slogan: “Here. Until Parkinson’s Isn’t.”  Michael J. Fox founded the organization in 2000, and the organization has since raised a mind-boggling amount of dough for Parkinson’s research.  I couldn’t find the cumulative amount, but just for 2018, they plowed over a $100 million into research.   Since 2014,  MJFF has helped push 14 new treatments for motor and non-motor symptoms of Parkinson’s through the complicated process to get FDA approval.  (In contrast,  before 2000, new Parkinson’s therapies were few and far between since levodopa was introduced in 1967.)

But back to your New Year’s resolutions.  I signed up for Fox Trial Finder and Fox Insight shortly after I got my diagnosis in 2012 because I wanted to do something.  For Fox Insight, I get a reminder in my email every quarter or so and am now up to my 17th study visit.  The survey usually takes less than an hour and includes questions about my motor and non-motor symptoms, cognition, depression, current therapies, and other relevant Parky data.   My personal data is of course kept confidential and de-identified.

Having a body of data over time and across over 43,000 Parkinson’s patients is obviously valuable to researchers of a disease that varies so much from patient to patient.  Even if you don’t have Parkinson’s, you can sign up with Fox Insight as a control.

And same for Fox Trial Finder – both Parkies and non-Parkies  are needed to sign up so we can test new Parkinson’s drugs.  Here’s the pitch from the Fox Trial Finder signup page: “Clinical trials are a final and crucial step on the path to developing better treatments for Parkinson’s patients today. Around the world, between 40% and 70% of trials face delays because of a lack of volunteers.”  Volunteers – that means you (and me).  And this is pretty easy:  You provide some basic info (e.g., how far you are willing to travel, when was your diagnosis) and then you can browse current trials.  MJFF will also periodically send you potential matches.  It’s a good idea to check in on new trials every so often – say, like when you’re getting ready to see your neurologist.  That way, if you see a trial that looks like a good fit, you can ask your doctor about it.   Remember,  those drugs aren’t going to test themselves.

Happy New Year, and here’s to more progress fighting Parkinson’s in 2020!

 

A Bottle in Front of Me

Any Port in a storm…

“Better to have a bottle in front of me than a frontal lobotomy.”
 Attributed to Dorothy Parker, famous wit (and alcoholic) of the 1920s

This being the holiday season, a post about alcohol (and other mind-altering substances) seems appropriate.  Shortly after receiving my Parkinson’s diagnosis, I broached the question to my neurologist of whether I could continue to drink.  I hasten to add that I am a pretty light weight boozer – a half-glass of wine or a fine local craft brew with most dinners.  My neurologist paused (as only a physician can who long ago ceased to be surprised  by his patients’ questions) and finally gently replied, “Well, you’re already impaired…”  I guess a prudent patient would take that response to mean “knock off the booze”, but I figured that a small amount of alcohol was better for my mental health than quitting altogether.   And I have definitely cut back – no booze if I’m going to be driving somewhere after dinner.

Now I am happy to find out that I have been right all along – yes, drinking is good for you.  According to a recent article in in JAMA Network Open, “[s]everal epidemiologic studies have shown that consumers of moderate amounts of alcohol have a lower dementia risk compared with nondrinkers.”  I’ll drink to that!  Even better, the article goes on to say that more frequent low-quantity drinking (the kind that I do!) reduces dementia risk more than less frequent high-quantity drinking.

As for other mind-altering substances that could be good for Parkis, of course you could see this coming – marijuana.  But not just any weed — these days it is important to distinguish between THC (delta-g-tetrahydrocannabinol – the marijuana component that makes you a stoner)  and CBD (cannabidiol – the marijuana component that makes you mellow-yellow).  Scientists at University of Technology Sydney have discovered a marijuana component with the catchy name of HU-308 that lessons the tremors from dyskinesia.  (These jerky, involuntary movements can be a symptom of Parkinson’s but are more typically a side effect after taking levodopa for several years.)  HU-308 is a component of  medical marijuana but without the “high”.   Senior author of the study Professor Bryce Vissel said, “Our study suggests that a derivative of HU-308, either alone or in combination with amantadine [the only existing drug for dyskinesia], may be a more effective treatment for dyskinesias and a much better option than using an unproven potentially harmful substance like cannabis.”  Professor  Vissel went on to warn: “Currently there is limited evidence about the effectiveness of medicinal cannabis. One problem is that no cannabis preparation is the same and cannabis has numerous effects, some of which may not be beneficial in Parkinson’s disease.”

This was from a 2018 post about dementia but I couldn’t resist repeating it.  Tasteless joke of the day: An old man was asked, “At your ripe age, what you prefer to get – Parkinson’s or Alzheimer’s?” The wise one answered, “Definitely Parkinson’s. Better to spill half an ounce of Crown Royal whiskey, than to forget where you keep the bottle!” …

Mambo Italiano

With a name like Kennedy, I can’t pass myself off as Italian, but I love all things Italian — pizza, pasta, truffles, and the Leaning Tower of  Pisa.  Hmm…scratch that last one.  Way back in 2001, I saw the tower and it struck me as odd that we celebrate such a really poor job of engineering.  Even in the 13th century, they must have known you don’t built a multi-story tower in a swamp.

And now I have a new reason to not be a fan of the Tower of Pisa.  My doctor tells me I have “Pisa Syndrome”.  For one brief happy moment, I thought he meant my only cure for Parkinson’s was to eat pizzas the rest of my days.  But nope, that’s Pisa with an ‘s’, not a ‘z’.  And you have already probably guessed that “Pisa Syndrome” is a classy way of saying I lean when standing, usually without being aware of it (as in the picture on the right).  I was quite chagrined that I was crooked in many shots from my September travels, even when I was consciously posing and (I thought) standing up straight.

One of the weird things about the Pisa Syndrome is that it seems like all the researchers are Italian!   Would you feel differently about your neurological team if they had sexy  names like  “Paolo” ,”Gabriella” and “Carmine”?  Alas, the research still comes out pretty dry and unhelpful:  “[Pisa] thought to be caused by alterations in sensory–motor integration pathways; …a[nother] …hypothesis emphasizes the role of anatomical changes in the musculoskeletal system. Furthermore, several drugs are reported to induce Pisa syndrome….”   My translation: we haven’t a clue what causes it  or how to treat it, try knocking off certain drugs.

I have been fighting this loopy posture for at least three years.  As my neurologist puts it, it is not helped very much by “pharmaceutical therapy” (i.e., drugs).   Instead, I  have been working for the last couple years with a personal trainer, and just signed up for my third tour of duty with her.  Being conscious of where your body is in space is difficult for most of us who are not (say) professional athletes or ballet dancers.     For me, it’s beyond difficult…baffling, perhaps….but I sense I’m getting more aware of how I’m standing/sitting/walking/cutting the vegetables at the kitchen counter, and I think my posture is getting better.  It goes all to hell when I get tired, so taking care of my fatigue  is part of monitoring my posture.  The single hardest motion for me to do?  Brushing my teeth.

YouTube extra:  Writing this blog requires exhausting, exhaustive research – such as: who has the best version of Mambo Italiano? Dean Martin?  Rosemary Clooney?  Bette Midler?  Sophia Loren?  Bette, hands down.

When “Transparency” means “Obfuscation”

Laura volunteering for a Parkinson’s research project.

Every morning I go to the front door, get the newspaper, read the headline, and almost always find myself exclaiming, “What an idiot!”  And here’s an example of a headline that gets that response: “EPA Plans Limit On Evidence Used For Health Rules”.

Yes, our anti-science administration has issued a proposal called (in perverse government-speak) “Strengthening Transparency in Regulatory Science”.  Transparency?  Like how did the researchers arrive at their conclusions?  Well, gee, that sounds okay…?  Except that “transparency” will be achieved by requiring that scientists disclose ALL of their raw data, including confidential medical records — and patient names.

It is difficult enough to get volunteers for Parkinson’s and other medical research.  Not being able to assure participants of confidentiality regarding their personal medical information would chill research.  That’s why the CEO of Michael J. Fox Foundation (MJFF), Todd Sherer, PhD, was one of five scientists testifying against this proposal, stating, “The proposed EPA rule requires study volunteers make a choice: waive their privacy or their desire to participate in key research. ”

I routinely participate in Parkinson’s questionnaires and other research —  physical characteristics (age, gender, race, etc.) may be collected but not my name.  My identification is not relevant to an epidemiological study.  The EPA says disclosure of raw data would allow conclusions to be verified independently, but this is a smokescreen.  Research is verified for publication by examining the methods used to arrive at a conclusion.   Epidemiological studies are commonly replicated.

The New York Times reports , “The measure would make it more difficult to enact new clean air and water rules because many studies detailing the links between pollution and disease relay on personal health information gather under confidentiality agreements.”   And oh yes – the EPA is considering applying this proposal retroactively.

So how do we block this non-transparent obfuscating rule?  MJFF reports on 11/13/19,  “The MJFF public policy team is working in Washington, D.C. on this issue, and will provide comments on the rule when it is updated for review.  There also may be a time for public comments in the future, and we will share information about how you can weigh in on this issue. ”

In the meantime, sign up for Fox Insight if you haven’t already.  We’re not going to let that idiot prevent us from finding a cure for Parkinson’s.

It’s all in your gut

View from the Salzburg Krankenhaus (Hospital)

Die Arst! Schnell!  Mein Blindarm ist kaput!
I can still remember frantically looking up words in my Berlitz dictionary as I yelled for a doctor when I realized my appendix was rupturing.  (Why in German?  I was in Salzburg, Austria as a college student.)

My Blindarm (appendix) is long gone and it turns out that could be a good thing.  I was fascinated by an article describing recent research that concluded that an appendectomy could be  associated with a reduced risk of Parkinson’s disease (PD).  But then, I did some more research and found that other studies say an increased risk or no correlation at all.

Epidemiological studies (that is, studies of diseases in a population) are very common in PD research, as a way to tease out disease patterns and potential causes.  I am gradually learning some simple validity checks for these type of studies:
1.   How big is the sample that researchers used to come to this conclusion?
2.   Correlation does not necessarily mean causation, but do the researchers have a theory why the factors under study might be related?  (in this case, PD and appendix).
3.  Has any one else done research in this area?

I should have done the third check first.  Turns out there has been a lot of research on whether removing your appendix reduces your PD risk, and  the conclusions are all over the map:

Date	Sample size	Researchers	Conclusions
7/30/2015	295	Centro Hospitaler de Porto (Portugal) Mendes, et al.	“Apparent relationship was observed between appendectomy and PD onset in the late [onset] PD cohort”
5/31/2016	42,999	Shulman Movement Disorders Ctr, Toronto (Canada), Marras et al.	“Appendectomy in mid or late life does not appear to be associated with a reduced risk of PD”
9/13/2016	1,597,548	Aarhus Univ, Aarhus (Denmark) Svensson et al.	“Appendectomy was associated with a small increase in PD risk 10 or more years after surgery.”
2017	1,625	Ankara University, Ankara (Turkey), Yilmaz et al.	“study suggest[s] no effect of appendectomy on the emergence and clinical manifestations of PD. The removal of the appendix is possibly not sufficient to suppress the exposure of the brain stem to alpha-synuclein
10/31/2018	1.6 million	Van Andel Research Institute (VARI), Grand Rapids, MI (USA), Killinger et al.	” We observed that removal of the appendix decades before PD onset was associated with a lower risk for PD, particularly for individuals living in rural areas, and delayed the age of PD onset.”

Why is there so much interest in the relationship between PD and the appendix? Because  the appendix is lousy with alpha-synuclein, the bad-boy protein that “causes” PD.  (“causes” in quotes because this is a bit simplistic.)    The latest research group listed above, the VARI team reported that” high amounts of alpha-synuclein were found  in nearly every sample of appendiceal tissue …, including normal and inflamed tissue, tissue from individuals with PD and those without, and tissues from young and old individuals.”  So how come, if everybody has alpha-synclein, why don’t they all have  PD?

In a startling hypothesis, VARI researchers (and others) think  PD may start in the appendix and work its malicious way up to the brain.  For those of us who now have PD, this implies there must have been some sort of trigger (environmental, perhaps?) that released this bad boy from the appendix.

“The vermiform appendix was once considered to be an unnecessary organ. Although there is now good evidence that the appendix plays a major role in the regulation of the immune system, including the regulation of gut bacteria, our work suggests it is also mediates risk of Parkinson’s,” one of the VARI research leads, Dr. Vivianne Labrie, said in the article.   The contradictory conclusions of these different studies are confusing, but in the meantime I’m upping my consumption of all those good “gut” foods like yogurt, sauerkraut, and kimchee.

Doctors are human!

News flash!  Doctors are human!  I think we are way past the Marcus Welby image of a physician as the calm, cool, rational being who can do no wrong and whose diagnoses are logically arrived at and always correct.

I have written before about the diagnostic process for Parkinson’s.  PD (and for that matter, most neurological diseases) is difficult to diagnose because there is no lab test, no biomarker, and PD symptoms (e.g., constipation, depression, muscle pain, tremor, etc., etc.) are not unique to PD and may present in many other diseases.

In addition to these scientific challenges, I hadn’t thought about emotional obstacles to accurate diagnoses until I read an article about misdiagnosing another neurological movement disorder, ALS (amyotrophic lateral sclerosis, aka “Lou Gehrig’s disease”).   The specific errors the researchers found are not relevant here; what is fascinating is the errors’ classification into four categories of “cognitive bias”:
–availability heuristic (i.e., the diagnosis of a current patient is biased by the clinician’s experience with previous cases),
–anchoring heuristic (i.e., relying on the initial impression despite the emergence of evidence that may contradict it),
–framing effects (i.e., subtle cues and collateral information bias the diagnosis),
–blind obedience (i.e., undue reliance on test results or expert opinion).  

The only thing worse than being wrong…

Marie Curie

The only thing worse than being wrong…is being wrong twice.   I just published a blog post about Marie Curie, writing how I had been wrong in several factoids about her.  Less than 12 hours after publishing, my sharp-eyed readership has (gently) pointed out I still have some facts wrong.

For starters, Marie Curie died at 67, not 77.  She was born in Warsaw, Poland on November 7, 1867, and died in Savoy, France on July 4, 1934.  I simply did my math wrong.  I persist in the baby  boomer conceit that I should be able to do simple math in my head.

I also am guilty of sloppy research by making the assumption that, since Marie Curie died at (I thought) 77 “after a short illness”, she simply died of old age, and not exposure to radiation.   My readership informed me that she actually died of aplastic anemia.  When I was more precise in my Internet search (“What did Marie Curie die of?”), I got a more precise answer:  “Curie died on July 4, 1934, of aplastic anemia, believed to be caused by prolonged exposure to radiation. She was known to carry test tubes of radium around in the pocket of her lab coat. Her many years working with radioactive materials took a toll on her health.”  So much for wearing a lead apron or lead shielding.

And another factoid about Marie Curie’s health:  When she finally earned enough money in Poland to study at the Sorbonne starting in 1891, she was still in precarious financial shape and survived largely on tea and buttered bread.

My previous post had said Marie Curie did not invent x-rays as I had previously thought.  This is true, but she did promote the use of x-rays.  In the same bio that includes the tea and bread factoid , I find the line:  “She championed the use of portable X-ray machines in the field [in WWI], and these medical vehicles earned the nickname “Little Curies.” .

One more tweak to my journalistic accuracy:  “Curies” are indeed a unit of measure for radioactive activity, but have been replaced as the official radiation unit by the becquerel since 1975.  Why?  The becquerel is more generic, defined as one nuclear decay per second , while the Curie is tied to radium: “quantity or mass of radium emanation in equilibrium with one gram of radium”  The becquerel was  named after Henri Becquerel, the discoverer of radioactivity.

 

What’s Marie Curie?

Marie Curie

It’s happened again.  I went to a specialty dentist to get my very first crown and they needed to take x-rays.  The technician dutifully wrestled the lead apron onto me and I said “I think of Marie Curie every time I get the lead apron.”    The technician looked at me blankly and asked “What’s Mahreekuree?”  “Not what – who.   You know, Marie Curie.”  The blank look continued.

This blank look has happened in pretty much every dental and medical office where I’ve gotten an X-ray.  So I have my Marie Curie patter down:  ” You know, Marie Curie.  First woman to win a Nobel Prize.  Inventor of the x-ray.  The power of x-rays are measured in ‘Curies’.  Unfortunately, Marie Curie didn’t know about the carcinogenic risks of exposure to radioactivity and how lead shielding would reduce the risk.  So she died of cancer.”   I always wonder if x-ray technical training includes any of the fundamentals about who came up with x-rays in the first place and why lead aprons are necessary.

I should not be so arrogant.  After some in-depth sessions with my research assistants, Dr. Google and Dr. Wikipedia, it turns out I am wrong about nearly everything in my Marie Curie patter.  Yes, Dr. Curie was indeed the first woman to win a Nobel Prize: In 1903, two years after Nobel Prizes started being awarded, Marie Curie shared the Nobel Prize in Physics with her husband, Pierre, and Henri Becquerel .  Bequerel discovered radioactivity in 1896 and inspired the Curies to research radioactive elements.  Marie developed methods to separate radium from radioactive residues in sufficient quantities so that its therapeutic properties could be studied.  Marie Curie remains the only woman to have received more than one Nobel Prize:  She also received a Nobel Prize in 1911, not in Physics but in Chemistry, for her identification of two new elements: polonium (named after Marie’s birth country of Poland) and radium.

So I got the Nobel Prize sort of right – I didn’t know about the second Nobel Prize.  But Marie Curie did not invent  x-rays.  X-rays were discovered and developed in 1895 by Wilhelm Conrad Roentgen (1845-1923) who was a Professor at Wuerzburg University in Germany.  The discovery of mysterious rays that could see through skin was such a medical sensation that in June 1896, only 6 months after Roentgen announced his discovery, X-rays were being used by battlefield physicians to locate bullets in wounded soldiers.  The radioactive elements that Marie Curie isolated were used in x-rays, and she may have used x-rays in her work,  but she  didn’t have anything to do with inventing x-rays.

So does the unit of measure “curie” have anything to do with x-rays?   Short answer: No.  Curies measure ionizing radiation.  X-rays are measured by so many parameters and units of measure that my liberal-arts-major eyes quickly glaze over, but none of the units of measures are “curies”.

So what about the lead aprons and Marie Curie dying of cancer?  I don’t know what Marie Curie died of, but she didn’t die until the ripe old age of 77 “after a short illness”, so this doesn’t sound like cancer to me.  The lead aprons?  The early adopters of x-rays were apparently blithely unprotected, but by the 1920s, the risks of radiation were becoming evident and lead shielding against x-rays became commonplace.   Did Marie Curie wear a lead apron?  Gosh, I hope so, but my research assistants were unable to verify.

Final question:  In a blog about Parkinson’s, why am I writing about Marie Curie?  Neither x-rays nor radioactive elements are relevant to Parkinson’s.  But Marie Curie sounds like a really interesting scientist, and I should respect her contributions by getting my facts right.  This post is also a reminder to myself to be grateful for the fundamentals and the early  research that we build today’s scientific research upon.

Oops…read my next posting with corrections.

YouTube extra:  A biopic of Marie Curie, “Radioactive”, starring Rosamund Pike,  premiered at the Toronto International Film Festival on September 14, 2019, and is scheduled to be released by Amazon Studios in 2020.  Check out the trailer.

 

Think Pink

PINK1, Parkin, PARIS….Hmmm….sounds like….Oh, I don’t know…perhaps choices for pink-hued wallpaper?

Nope, turns out to be types of proteins important to brain health and to understanding Parkinson’s.

And, right away, my eyes glaze over, and I wish I’d paid a little more attention in my one and only biology class in 10th grade.  (Had they even invented genes back then?).

So let’s start with the basics:
–Genes?  Proteins?  Are these the same?
No — Parkin (say) is the protein and “the Parkin gene” means “the gene which contains the instructions for producing the Parkin protein.” Each gene tells the cell how to put together the building blocks for one specific protein. However, the gene (DNA) sits inside a different compartment of the cell (the nucleus) from the location of the cellular machines that make proteins (ribosomes). Therefore, the gene must first make a copy of itself (called messenger RNA – mRNA), which is smaller and more portable than DNA and is able to leave the nucleus to reach the ribosomes. A ribosome then reads ….the mRNA code and converts the instructions …to form a protein., Usually, when a protein is not properly produced, it is because there is some mutation in the gene which contains its instructions.

–What’s with the cute names of proteins?
You will never get that Nobel Prize in Chemistry without a cute acronym:
PARIS: Parkin-Interacting Substrate protein (PARIS)
PINK1:  PTEN-induced kinase 1  (aren’t you sorry you asked)
     Parkin:  Named after you-know-who.

–What’s the deal with these three proteins?
A recent study links PARIS with the two other proteins in a pathway that protects dopamine-producing brain cells from death.  Damage to these proteins can lead to abnormal activity in the mitochondria (energy powerhouse of the cell) which results in cell death.  (Bye-bye dopamine produced by these cells.)

–Yeah?  So what?
The study lead, Ted Dawson, MD, PhD, found that intervening on the PARIS protein, which links these two proteins and dopamine cells, reversed cell death in both rare genetic forms of PD and sporadic PD, in which the cause of the disease is unknown.

–So does this mean Parkinson’s is genetic?
Not usually.  Only about 15% of Parkies (not me) have genetic mutations that are tied to PD.  (Seventeen new gene mutations were just identified in 2017!)  But understanding the cellular/genetic  mechanisms of PD helps all of us Parkies.

YouTube bonus: “Think Pink”, From the 1956 movie Funny Face  (an unfortunate waste of the talents of Fred Astaire and Audrey Hepburn, neither of whom show in this number.  But you gotta love all those fitted suits, gloves, and hats.)

Challenge accomplished!

My backpacking challenge was accomplished!  But not quite as I anticipated.

I was honored to join the PassToPass.org on a Pacific Crest Trail backpack  and meet people both courageous and interesting:

Martha and John Carlin — After John got a Parkinson’s diagnosis in 2002, Martha started educating herself about the disease and eventually founded a company, The BioCollective, to research the human biome and help find a Parkinson’s cure.  She matter-of-factly told me,  “We collect poop.”

Steve Peters — With the slow, small steps of someone who has had PD for a long time, Steve persevered on the trail.  Perseverance even though his son (and support person) couldn’t get time off from work and had to drop out at the last minute.

Derek and Seth Torry — Derek, diagnosed at 40 with YOPD (Young Onset PD), and his son Seth were the wranglers for four llamas.

Lori and Laura still smiling on the trail!

Laura and Garth Hitchens — A bright, bubbly woman with an excellent first name, Laura got her diagnosis at 51 and is active in YOPD activities.  Her husband Garth came as her support person.

Lori Schneider — Her trail name is “Seven”.  Why? Because she’s summited the highest peaks on all seven continents — all with multiple sclerosis.

Bill Meyer at our campsite.

Bill Meyer and Mort — Bill is one of the founders of PassToPass.org.  Just a few days before this hike, Bill had the battery replaced (under the skin) for his DBS.  His doctor forbade him from carrying any weight, so Bill’s brother-in-law Mort stepped in to help carry Bill’s stuff.

And how did I fare?   After many tryouts, my fifth backpack, which I  borrowed from a friend (Thanks Jan!), fit me reasonably well.  The first day I had the luxury  of having the llamas carry my sleeping bag and food bag.  But after a sleepless night in a claustrophobic tent, I persuaded Paul to hike out the next day.  “I can do this, ” I thought, based on the information I had: 11 miles, all downhill.

Note my weary expression and leaning posture, after about 3 miles of unexpected elevation gain. Mt. Hood in background.

Ha ha.   Much to my surprise, there was plenty of elevation gain and almost equally taxing elevation loss.  The “elevation loss” info I had was a net amount.  And the distance was more like 12 miles.  And of course, since we had separated from the group, we couldn’t make use of the llamas,  My handsome sherpa came to the rescue.  He was already carrying the tent, stove, fuel, cooking pot, and water purification.  He added one of the back chair pads and for the last three miles, he carried my sleeping bag in his hand.   And for the final mile, he came back to carry my whole pack.  What a guy!

So, not quite what I anticipated.   But hey,  three days’ distance in two days!  Guess I need to figure out a strategy how to sleep on the ground.