Something to Brag About!


As some of you may recall, I have a neuro-muscular disability called Charcot-Marie-Tooth Disease, CMT for short. My daughter also has it. For that reason, my husband and I belong to the CMT Association, which is leading the race for a cure. Each year, we take part in the annual Walk 4 CMT in September to raise funds for critical research.

2017 group walk 4 CMTA

Dallas Walk 4 CMT 2017

Yesterday, I received an email from our branch leader announcing the results:

THANK YOU all for being a part of the Dallas Walk 4 CMT 2017! Each of you are an integral part of our success. . . .

YOU helped make the Dallas Walk 4 CMT a tremendous achievement. This year, a record 110 people took part in the festivities at South Lakes Park and together we raised over $9,600 for the CMTA towards ending CMT! We could not have done it without you. Cheers!

Nationally, the Walk has raised close to $160,000, and still growing. Hooray!

If you would like to find out more about CMT, go here:

https://www.cmtausa.org/understanding-cmt/what-is-cmt/

Advertisements

A Meeting with Dr. Charcot


Friends, as some of you know, I have a hereditary neuromuscular disorder called Charcot-Marie-Tooth disease. It has nothing to do with teeth! Dr. Tooth was a British physician who diagnosed CMT about the same time as Dr. Charcot and Dr. Marie in France, in the 1880s. Dr. Charcot is considered the father of modern neurology. This article was sent out by the CMT Association to members, of which I am one.

By Susan Ruediger

Dr. Charcot's grave

1-800-606-2682 | info@cmtausa.org | www.cmtausa.org

Research Progress on Charcot-Marie-Tooth Disease


CMT shark logo

As some of you know, I have CMT, a hereditary disease that I’ve traced back at least five generations in my father’s maternal line. There’s a lot of research being conducted into the 80+ genetic causes of this neuromuscular disorder, much of it sponsored by the CMT Association’s STAR program (Strategy to Accelerate Research.) The various research projects are funded largely by donations from individuals and families who know firsthand what it’s like to live with the debilitating effects of CMT. I recently received an update about research progress, which I’d like to share with you all today.

First, here are some enlightening statistics taken from Wikipedia.

“Charcot–Marie–Tooth disease (CMT), also known as Charcot–Marie–Tooth neuropathy, hereditary motor and sensory neuropathy (HMSN) and peroneal muscular atrophy (PMA), is a genetically and clinically heterogeneous group of inherited disorders of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. Currently incurable, this disease is the most commonly inherited neurological disorder, and affects approximately 1 in 2,500 people[1][2] equating to approximately 26,000 people in the United Kingdom and 128,000 people in the United States. CMT was previously classified as a subtype of muscular dystrophy.“

More from the Mayo Clinic:

Charcot-Marie-Tooth disease is a group of related conditions all caused by inherited mutations in genes involved with the structure and function of the nerves that serve your feet, legs, hands and arms.

In some cases, these genetic mutations result in damage to the nerve itself. Other mutations damage the myelin sheath, the protective coating that surrounds the nerve. The end result, however, is the same — weaker messages traveling between your extremities and your brain.

Now here is the 3rd Quarter Research Update through September 31, 2015 from CMTA’s CEO, Patrick Livney. (technical but enlightening)

CMT1A (most common form, believed to be the culprit in about 60% of CMT cases)

· Sanofi-Genzyme completed 1.9 million compound screen early in the year. Further work distilled the results down to 742 active compounds. Continuous triage will bring this number down even further over the next quarter. Pilot sets of compounds are being tested using stem cell-derived human Schwann cells (G. Lee, Johns Hopkins), myelination assays in culture (L. Feltri, Univ. of Buffalo), and in primary Schwann cells.

· We initiated a collaborative development of serum biomarkers for CMT1A together with Genzyme. Serum samples are being collected at the University of Iowa. Joint meeting with Genzyme is being planned for November.

· An Addex compound that regulates a target implicated in Schwann cell myelination is being evaluated in studies in CMT1A rodent models.

· An agreement with licensing rights was completed with Affectis Pharmaceuticals to work on a compound that regulates P2X7, a cell surface target on Schwann cells that may regulate myelin formation. This has entered testing in CMT1A rodent models.

· Signed an MTA (Material Transfer Agreement) with AbbVie for use and data on their P2X7-directed compounds.

· The Amgen proteasome inhibitor is currently in testing in rodent models of CMT1A.

· On-going discussion with ISIS to use their custom molecules in an in vivo study. Study has been initiated in a rodent model of CMT1A and samples are being analyzed.

· NCATS (National Center for Advancing Translational Science) has completed a 400,000 compound screen. Svaren laboratory finished a new assay to establish specificity for PMP22 lowering (intended goal) vs. MPZ or Myelin Protein Zero lowering (which would be a negative side effect). Trish Dranchak at NIH has tested and validated this assay. This assay has been used on approximately 10,000 cherry- picked compounds from NCATS screen to identify specific inhibitors of PMP22 expression that do not affect the vital MPZ myelin component. The secondary screen is now completed and under analysis.

· Pfizer provided an additional ~250 compounds from their chemogenomics library that had shown promise of reducing PMP22. These compounds were tested in both PMP22 and MPZ assays listed above. Screen was completed, and we are awaiting Pfizer’s “decoding” of the results.

CMT 2A:

· Creation of a CMT2A target discovery and drug screening assay has been completed and validated by Brittany Wright (NCATS). It is now ready for pilot screening.

· The next phase of CMT2A projects is being developed:

o Characterization of two mutant rats (H361Y and R364W) by behavioral, electrophysiological and pathological studies, to be done by PsychoGenics and Dr. Steve Scherer in collaboration with Renovo.

CMT 2E

· Dr. Liem has demonstrated under a microscope that there are neurofilament clumps evident in the CMT2E mutated mouse that are not evident in the normal or wild-type mouse. He has also shown this in neurons derived from the mouse embryonic stem cells from this model, which has enabled at least limited testing of small compound libraries at Columbia University.

· Mouse colony for CMT2E has been established at PsychoGenics, and phenotyping results (observable traits or characteristics) indicate measurable deficits. Dr. Steve Scherer has also written a proposal to characterize when the mutant mice develop neuropathy, by electrophysiological and pathological studies.

· A number of investigators with experience in disorders related to CMT2E gathered in Chicago for a one-day meeting. A number of relevant results were presented and several initiatives for future efforts for CMT2E were proposed.

CMT 1X (the type that runs in my family)

· Dr. Martini, in collaboration with Plexxikon Pharmaceuticals, has completed a study with an anti-inflammatory compound on a CMT X animal model. His published studies indicate that this approach has positive results in both CMT1X and CMT1B.

· Dr. Scherer has put forth a proposal from Dr. Brett Morrison, which is being reviewed by the STAR Advisory Board (both Science Experts Board and Translational Experts Board)

CMT 1B

· Dr. Brittany Wright, in collaboration w/ Dr. Shy’s lab, has built three cell lines associated with the activation of UPR (Unfolded Protein Response), which is believed to be the cause of this disease state. Assays being worked on currently to detect such activation.

· Dr. Wrabetz on track in building CMT1B mutated mouse model.

CMT 4

· Dr. Scheideler and STAR team have considered several presentations made by investigators across the various type 4s. Looking for commonalities and proposals on translational projects to fund. Working on putting together CMT Type 4 STAR team.

· Dr. Kleopa has put together a proposal for CMT4, which is being reviewed by the STAR Advisory Board (both Science Experts Board and Translational Experts Board).

STEM CELL Effort

· Dr. Shy sent 18 fibroblast-derived cell lines to the New York Stem Cell Foundation (NYSCF), which were used to produce iPSCs (adult stem cells). These cell lines have been mostly completed by the beginning of September. Once created, the STAR team will work to differentiate these cells into Schwann cells (1A) and neuronal cells (Type 2). Dr. Baloh has begun a project for 2A and Dr. Gabsang Lee has begun project for 1A. Goal is to create a human assay suitable for evaluating potential targets of therapeutic intervention.

If you have questions pertaining to this STAR update, please contact Patrick Livney: pal@cmtausa.org or 1-312-750-9800.

Demolition Day One


Oh my, what a day we had yesterday. Did I tell you we’re having our bathrooms and laundry room updated as well as the kitchen? No? Well, we are, and the fun began with a bang yesterday. Err, make that a lot of bangs, growling saw blades and mess. Big time mess!

It started with our guest bathroom. We’re having both bathroom doorways widened to accommodate a wheelchair. This is due to my CMT, which will undoubtedly put me in a chair within a few more years. (See “Two-Finger Typing”)

photo 15      photo-18.jpg

Newly cut, wider doorway, waiting for new door and frame; wood floor in the hallway also must be repaired. Luckily, we have a few extra boards left from when the floor was installed.

 

photo 9        photo 16

Divider wall also had to be cut back a few inches.  I’m losing my pretty seaside wallpaper border. Darn!

Next came the laundry room, where the plumbing needs to be rearranged to accommodate our new washer. We had an old top loader before, which worked fine with the placement of the water and drain pipes. But the new one is a front loader, as is the dryer, and in their present position the doors open against each other, making it difficult to switch clothes from the washer to the dryer. With my unsteady balance this is a real problem. Thus, we’re having the water and drain lines moved so we can switch the washer and dryer.

photo 12        photo 19

Pretty new babies need switching; wall opened up, showing water line that needs to be moved over, happening today. I wonder when the wall will be put back together. I can’t wash clothes until this and the new floor tiles are done. Hubby and I foresee a trip to a laundromat in the near future. It’s been years since we visited one, but I remember it being a weekly stop back in the day, when we were newlyweds. A century or two ago.

This only the beginning. Next week the kitchen demo starts. Oh joy!

Two-finger Typing


Six Cats In My KitchenToday I’m kicking off a new blog feature. Let’s call it “Mid-Week Meanderings”. I’ll try to post an installment once a week, usually on Thursday, but I may miss a week now and then due to writing or family demands.  Sometimes I’ll tell you tales about my feline children. Other times, I might share favorite recipes. Often, I’ll share family stories and bits of my life experiences.

To begin, let me tell you a secret: I’m a two-finger typist. An author who hunts and pecks, that’s me.

I learned the traditional way of typing in high school. The fastest I ever got was about fifty words a minute. Not great but okay since I didn’t plan to be a professional typist. In those day I had my heart set on becoming a fashion illustrator, a goal I attained after four years of art school, a career I was forced to abandon as my hands grew too weak to hold a pen or brush steady.

You see, I have a disability inherited from my father. If you’vJean-Martin Charcote read my memoir Six Cats In My kitchen, you already know about it. If not, let me fill you in.

My family curse is called Charcot-Marie-Tooth disease — CMT for short. No, it has nothing to do with teeth! It’s a neuromuscular disorder named after three doctors who first diagnosed it in the late 19th century. Dr. Jean-Martin Charcot was a French neurologist. He is known as the founder of modern neurology. Pierre Marie was his resident. They announced their findings along with a Brit named Howard Henry Tooth.

So what is this disease with the weird name that you’ve never heard of? According to the Charcot-Marie-Tooth Association, “CMT is a group of inherited disorders that affect the peripheral nerves, which are the nerves outside the brain and spinal cord. There are more than 70 kinds of CMT. Each kind is caused by a different genetic mutation, and more causes are being discovered every year.”

CMT is also called peroneal muscular atrophy. It affects more than two million people worldwide.

CMT foot

CMT foot — No it’s not mine!

Typical symptoms of the disorder

  • Weak ankles
  • Foot drop
  • High arches
  • Hammer toes (curled downward)
  • Very thin calves.

CMT can also affect the lower arms and hands, causing muscle atrophy. The arms become thin, thumbs lose strength and fingers eventually develop a clawed position. By that, I mean it becomes impossible to straighten them, explaining the title of this post. For many years now I’ve only been able to type with my two forefingers – hunting and pecking.

See more CMT photos here: http://tinyurl.com/nykwqx6

Surprisingly, I can type over thirty words a minute when simply copying a paragraph or two, fast enough to pass a typing test a decade ago when I toyed with the idea of working in a local branch library. I actually interviewed for a job there, but after learning I’d need to be on my feet all day I realized it wasn’t possible. Nowadays I type on a laptop computer, slowly pounding out my latest book.

Not to worry, though. Speed isn’t important. I’d write slowly even if I could type 120 words a minute. My stories don’t come pouring out like a river on a downhill grade. They trickle out one drip at a time. That’s not ideal in today’s speed-of-light indie publishing business, but what can I say? I’m a perfectionist, always have been. I fuss over every word, every sentence, every paragraph. Thus, my “handicap” isn’t really a problem.

Some people have poor eyesight, some poor hearing or other health issues, but humans are amazing creatures. Most of us make the best of our God-given abilities and find ways around our disabilities, whatever they may be.

How about you? Do you have a quirk of nature that affects your job, your family or activities?

http://www.amazon.com/lyn.horner.award-winning.books

Six Cats In My Kitchen  http://www.amazon.com/dp/B004VXM0TQ

Obama Care: What do you think?


I have never blogged about political topics because I don’t want to offend and alienate anyone, but I’m making an exception today. This may get me in hot water, but I’m willing to take that risk for something I strongly believe.

First, let me tell you a story from my childhood. My parents were poor, my father disabled with Charcot-Marie-Tooth disease, a hereditary neuromuscular disorder that I and my daughter also have. Daddy was often out of work. Most of the time we had no health insurance, but because we lived in Minnesota, a liberal state, I never went without health care. As a teenager, I underwent several operations to stabilize my ankles and allow me to walk more easily, without often falling and injuring myself as I did before the surgeries, These surgeries were done at the outstanding University of Minnesota Hospital, through the orthopedic department.

Who paid for my expensive operations and follow-up care? The state, meaning the Minnesota tax payers, to whom I am forever grateful. But what if “Obama Care” had existed back then? Could my hard-up parents have afforded a little each month to pay for health insurance? I don’t know, but at least they would have had that option.

So, do you see why I believe everyone, no matter their income level, should have health care coverage? I’m not saying the Affordable Care Act is perfect. There will certainly be problems and changes needed. But in my very humble opinion, that’s far better than the screaming match going on in Washington, with both sides pointing fingers at the other and tossing out all manner of exaggerated statements – for obvious political reasons.

What do you think?

What is Charcot-Marie-Tooth Disorder (CMT)?


“Charcot-Marie-Tooth, or CMT, is the most commonly inherited peripheral neuropathy and is found worldwide among all races and ethnic groups. Discovered in 1886 by three physicians, Jean-Martin Charcot, Pierre Marie, and Howard Henry Tooth, CMT affects an estimated 2.6 million people.” (Quoted from the CMT Association)

I have CMT type 1-X. I have traced it back at least four previous generations in my father’s family. This is a slowly progressive disorder, affecting more and more nerves and muscles as the person ages. For more information about CMT please follow this link: http://www.cmtausa.org/index.php?option=com_content&view=article&id=70&catid=10&Itemid=41