Tinkles and a Journey

INSTRUMENTS (#4)

The Tinkler Tinkles
post by hj mooij

The tinkler was first conceived as a noise maker, it's a simple design structured around an old bicycle wheel. The spokes are different tensions which produce different pitched tinkles when struck with a solid object.
It's really fun to play because there are a large variety of tinkles that can be produced. The spokes create differences in spacing at various distances from the axle which results in different rythums of tinkles. The wire frame is just for looks, but we did attach a small microphone to the frame and it made some really nice scraping sounds when played. I think it could be improved by creating some custom spokes made from different materials. . . the fun never ends.

CHARCOT MARIE TOOTH

Here is a wonderful post by Michele that is probably more pertinent to me than most, as I am to have a similar surgery next week. This is partly why I asked her to write it, but surgery is also a big question for people with CMT, weighing up the trauma and risk against alleviating pain and gaining mobility, so I wanted it discussed in this project... Either way I'm happy to hear and share Michelle's enthusiastic results (and steady myself for the patience I'll need). (Tim)

Michele has a great blog of her own if you'd like to read more: http://myjourneywithcmt.blogspot.com


My Journey Through Surgery
post by Michele

A year ago I set out on a journey, one that would be long and painful but one that should be very rewarding once I reached my destination. I am 29 years old and was diagnosed with CMT Type 1A in 2005. At that time, I met with a surgeon who could correct my insanely high arches, but there was a glitch...I wasn't ready! I wasn't even ready yet to know what CMT was. So I pushed it in a drawer and went on with my life. As time passed, my arches got even higher (my shoe sizes went from a size 6.5 to a 3!!) and the calluses in the balls of both my feet were worse. I had to go to the doctor on a monthly basis to have them shaved off and even then, I still hurt with every step I took. I also developed this terrible pressure pain on both thighs, my ability to walk or stand for long periods of time decreased, and I had no choice but to pull CMT out of that drawer and find the time to deal with it.

I did everything I could possibly do before having reconstructive surgery: physical therapy, acupuncture, several pairs of orthotics, expensive shoes, you name it. Life sometimes has a way of working itself out and I was moving to CT from NJ and had to quit my job. Since the job market isn't all that great and I didn't see any interesting jobs in my field (Marketing), I thought it would be a perfect opportunity to take time off and invest on my health by having two reconstructive surgeries, one on each foot.

I started my search for surgeons again around November 2009 and when I finally selected the best surgeon at the end of the year, he announced to me in January that he was retiring. I was frustrated and annoyed with him, but he promised that he would find me a great surgeon and that he would be there during both surgeries (and he kept his promise!). In February 2010, I met with Dr. Feldman, whom I immediately liked. He thought it would be a good idea to try an injection into my hips to see if it would help my thigh pain. Unfortunately the doctor that administered the injection hit a nerve and I was in so much pain that we couldn't go through with my March 17 surgery.

Finally on April 16, we were all set. No more delays. I had never been hospitalized or had any procedures done, so I was a bit anxious about diving into this unknown. On that day however, I was pretty calm. For me, the hardest part was making the decision. Once the decision was made, I was ready to go. I also prepared myself for the worst case scenario. I talked to several CMT patients who had undergone this surgery before me. I was ready for a year or longer in recovery. And most importantly, I was ready for the pain. The first night was extremely painful and difficult, there were a lot of tears. But I prepared for this journey with the support of family, friends, and loved ones, so I was not alone. Even though I live with my boyfriend, I prepared to spend about 2 months with my parents each time because they would be able to be with me almost all of the time. Believe it or not, time went a lot faster than I expected. Before I knew it, I could move again and I could start to step down with the walking boot. I returned home and started physical therapy. Within 3 months, my foot was no longer swollen (I mean, AT ALL). And almost immediately I could tell the difference between this new foot and the old foot, and was sure I had made the right decision.

Then, I started preparing myself for surgery #2, but this time, I felt more confident because I knew what to expect and the first surgery went so well. I knew what my timetable would be, how my body would react to the meds, I knew that even when time seemed to drag, that it would all fly by and I would be back to walking again. So we scheduled it for September 20. And just out of nowhere, 2 weeks before the big day, my surgeon's office called to move it to September 22, which wasn't a big deal but was kind of annoying. I point this out because life works in "mysterious" ways. One of the main things I have had with me through the process is faith - that everything would be ok. Six days before my surgery a recruiter reached out to me with a perfect job opportunity. And wouldn't you know that I interviewed on September 20 and 21, and actually landed the job!!!! They decided to wait for me for 2 and a half months while I recover!!! If this isn't a gift from above, I don't know what is.

Getting the job just made me want to get the process over with even more quickly. The first time around, I knew I would still go through a second surgery so I was pretty calm. But now that I have something to look forward to, I have been anxious for time to pass. It's now been 2 months since my second surgery and I've been moving around with the walking boot, soon I'll just be walking on my own.

I can't believe this year has gone by so quickly. I think it definitely has been my most trying year, by far. But as I get close to that finish line, I feel a sense of accomplishment. I really did what I set out to do. I feel that I am coming full circle. I won't say it's been an easy and rosy journey, it's been full of tears and many times over the summer, resentment that I could not go outside to enjoy my favorite season. But I'm almost done and I have learned so many lessons in life! Hopefully my new feet will be happier than my last ones and healthy for a long time to come!

Michele

Travel with the US Paralympic Cycling team

INSTRUMENTS
hj mooij has just launched a new website, it's pretty exciting...
http://hjmooijink.com/

Different Wands for Different Tones
post by hj mooij

Construction of the tinkler has begun and is progressing nicely. So far it features a side cut wheel hole for easy spinning and an open top for playing. A top cover will be created soon with a nice angled hole so one can play the tinkler with one or two hands while reaching the entire spectrum of spokes. The tinkler makes different tones with different playing wands, find your own or just use a nail, it all sounds great.

CHARCOT MARIE TOOTH

Anthony Zahn is a bike racer, a damn good one at that - He just won bronze at the Paralympic World Cycling Championships. He has CMT, and is a successful athlete with it, which is why I approached him to write a post. Anthony was very friendly and wanting to help with the project, yet this was his initial response: "I honestly don't have too much to say about CMT as I don't really dwell on it. I just try to get through my day and do what I have to do without thinking about things I can't control." I think that is inspiring in its self, but I'm very happy that he went on to write the following post describing his racing over the past few weeks to share a little of what's involved. (Tim)
[To see more pictures and news, follow this link: http://usparalympics.org/athletes/anthony-zahn/news]

Travel with the US Paralympic Cycling team
post by Anthony Zahn

Wow. What a week. Or three I think since I've been home. The summer's been a long blur. Starting in late April/ early May with 2 weeks of stage races in Spain and France, home for 2 weeks, a week in Oregon for road Nationals, home for a week, off to the Chicago area for 4 days of Superweek, straight to Colorado Springs for track camp and track Nats, home for 10 days, then back to Co for 10 days of prtp camp and off to 10 days in Baie Comeau Canada for Paralympic World Cycling Championships.

2010 Paralympic World Cycling Championships

This is a bit more travel than typical for the US Paralympic Cycling team, but it's what we do. There are about 18 American athletes here with various disabilities ranging from being born without a portion of an arm, to limbs missing from various injuries, to CP CMT (Me) and paraplegics. With all of the other countries thrown in, there are more injuries here than I think anyone can imagine. Many have full time jobs and use vacation and sick days to travel to one or two events per year, others are full time athletes, but everybody here lives and conducts themselves as a professional athlete.

The travel is a bit tough, for instance it took us four two hour flights to get here, our mechanics had to rent a truck for out bike to drive them from Montreal which took 11 hours, and our luggage didn't get here for another 3 days!

Hands down the hardest part is the 100 days or so per year away from home. That's about all there is to say about that.

The team is the greatest bunch of people though, which makes things a lot easier. Spending roughly 1/3 of a year together in 10 day to four week chunks could get pretty crazy but everyone on the team athletes and the 10 or so staffers are among the most professional and funny people I have ever met! Everybody knows when to be where, what to bring (and leave home) and what to do to make things run smoothly and win medals.

I'm done with racing now so I get to pack everything up to put on the truck for shipping, go watch the last few races and cheer for some teammates, go to the closing ceremony, find dinner somewhere in there, sleep for a few hours and hit the road to the airport for the first of another four flights home!

2009 Paralympic World Cycling Championships (Zahn on the right)

CMT Science #3 and the tinkler

I seems the instrument makers have rallied into action. I welcome hjmooij as instrument maker #4 – an outstanding noisey artist.


INSTRUMENTS (#4)
post by hjmooij

the tinkler

the tinkler is the instrument name.
hypothesis: it'll make tinkling noises

will start construction soon. updates as progress is revealed.





CHARCOT MARIE TOOTH
post by Tim Phillips

CMT Science #3: a summary of the research (why we're raising money)!

The discovery of the cause of CMT 1a, explained in the last post (CMT Science #2), led to an important research program, STAR (Strategy To Accelerate Research), initiated and funded by the CMTA. (Hence this project's fundraising). In case you forgot, the discovery was that in someone with CMT 1a, something called a Schwann cell is producing too much protein, which causes the insulation around the peripheral nerves to break down.

The STAR program was established to bring together leading Schwann cell researchers from around the world in order to work out how to stop the harmful over production of this protein, PMP22, in people with CMT 1a.

There are many creative scientists that are key to different stages of this research. The first big step was to create a stable cell line of CMT affected Schwann cells, this was engineered by Ueli Suter and his colleagues at ETH Zurich, Switzerland in 2009. (It was also Dr. Suter who initially demonstrated that the over-expression of PMP22 causes CMT 1a).

Once achieved, the next step was to test hundreds of thousands of compounds on the cell line to see if any of them reduced the production of the protein, PMP22. This is achieved quite ingeniously (at least to the non-scientist like me) with the help of high-throughput screening.


The picture above shows a Kalypsys robot at the NCGC (NIH Chemical Genomics Center in Rockville, Maryland) holds a 1536-well plate similar to those that will be used during the high-throughput screening (HTS) of the CMT 1A cell line. That means it can test 1536 samples at once.


Very basically, the stable CMT cell line is created in a Petri dish by combining affected Schwann cells with tumor cells, these regenerate so keep the cell line ‘alive’ or stable. The cell line has also been kitted out with carefully manipulated phosphorescence from fireflies! More specifically this is a florescent marker
called Luciferase. It naturally lights up as the protein PMP22 is produced, so the amount of light given off is indicative of the amount of PMP22 produced.

Image showing variance in emitted light from cells with Luciferase.

Now a machine, like the one pictured above, can take the cell line, test a compound on it and monitor if the light produced diminishes. If the light does diminish, then less protein PMP22 is being produced and the compound is a candidate for treating CMT 1a. The powerful machines at the NCGC (under the guidance of Dr. Jim Inglese, Dr. Sung-Wook Jang and Dr. Doug Auld), enabled the research team to test 350,000 drugs and other compounds in the NIH chemical library as reagent, this is high-throughput screening.

BIG NEWS!
The big news is that the first round of screening just finished and looks very promising. There were 810 candidates identified, 10 of which are already approved for public use. The next stage is a second round of testing for these candidates. In the meantime there are two other crucial projects being run concurrently.
- One, currently being undertaken by Klaus Nave at the Max Planck Institute for Experimental Medicine in Gottingen, Germany, is focused on developing a laboratory model of the disease to understand if the effects observed in High-throughput testing will also be observable in animals.
- The other, being pursued by John Svaren in his lab at the University of Wisconsin at Madison, is designed to further the understanding of how PMP22 is expressed and regulated and discover whether the same constructs will be observed in humans.

It is the combination of all this research that should make the STAR program both successful and efficient. STAR is privately funded by CMTA members, supporters, friends and family. Together, we need to raise $9 million over the next 3 years to complete the initiative. This is achievable with your help – please consider donating.


If you know of any recent publications or papers that discuss this work further, I’d love to read them – please add a comment with a link.


Links:
http://www.charcot-marie-tooth.org/STAR.php
CMTA’s description of the STAR program

http://www.charcot-marie-tooth.org/STAR_update3.php
Latest update



That’s enough science for now! The next post will be far more personal…