Kennedy's Disease Association

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"The web site acted as a central organizing influence for the sharing of information and brotherhood. Without the KDA, I was alone, as this disease is very rare and even my neurologist was less than fully knowledgeable."

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Kennedy's Disease Chat Transcript  03-21-2009

Topic:  Special Guest - J. Paul Taylor, MD, Ph.D

Host: Bruce Gaughran


Bruce: Morning Tood
Bruce: Todd
ToddAllen: Hi bruce!
Bruce: How are things?
ToddAllen: I was off surfing the net trying to prepare my questions for the chat.
Bruce: Good, Paul likes to be challenged
Bruce: Morning Shamar
ToddAllen: I'm hanging in there, although my deterioration has been more rapid and profound then I was prepared for.
shamar1228: morin
Bruce: I understand. Hopefully you will hit a plateau and level out for a little while.
shamar1228: so when does it hit hard
Bruce: I just went into a slide myself last week and it is frustrating because I don't know when I will come out and how deep it will go before I come out.
ToddAllen: It's been a bumpy ride. It's not an even across the body deterioration but several small injuries not healing.
Bruce: Sharmar, everyone is different. There is no set schedule. How old are you?
shamar1228: 36
ToddAllen: 37. :)
Bruce: A young man. Oh to be 36 again ...
ToddAllen: That is 37 is when it hits hard.../
ToddAllen: I'm 44.
shamar1228: lol
ToddAllen: Shamar, do you know your repeat count?
Bruce: I am 62 and have many slides and plateaus in my life and continue to ride the rollacoaster of life.
shamar1228: do u guys get bad headaches
Bruce: No
shamar1228: repeat count?
ToddAllen: I did get headaches while I was working - stressful job - but since I've retired it's not been a problem.
Bruce: Mine is 52
ToddAllen: My count is 50.
Bruce: The higher the count, the more the fun ... so they say
shamar1228: is that the kd test
Bruce: Yes
shamar1228: 46
Bruce: The CAG repeats
Bruce: Paul Taylor is quite good on these chats. He is a researcher and medical doctor and has been very supportive of the KDA.
shamar1228: what is your cpk counts
shamar1228: cool;
Bruce: Todd, are you warming up? We are in the 60's and 70's every day right now.
Bruce: CPK is in the 300's now. It was as high as the 800's earlier.
ToddAllen: My headaches were accompanied by a mental fog that made concentration difficult. The first thing that helped was getting a better eye exam and better glasses that helped correct a wandering eye problem. The second thing was improved diet and sleep patterns. I was chronically sleep deprived and relying on too much caffeine and sugar to function.
Bruce: Sounds like a chronic workaholic
ToddAllen: Our weather has been very volatile, snapping between freezing and low 60s every few days.
shamar1228: me also sleep deprived my cpk 2600
Bruce: I use to be at work at 6:00 AM and often wouldn't finish until 8 or 9:00 PM. I sure am enjoying retirement. The travel was the worst part of the job.
ToddAllen: I had a similar schedule with high pressure and constantly missed unrealistic deadlines...
Bruce: Our mills and warehouses were not friendly for someone who had difficulty walking long distances and climbing catwalks.
shamar1228: we get highs of 40
Bruce: Where are you located Shamar?
shamar1228: mn
Bruce: I was born and raised in Austin and lived in the Twin Cities for several years.
shamar1228: i worked in potato house changed to sugar whaehouse
ToddAllen: Bruce, do you have any sensory involvement, either numbness or chronic pain?
shamar1228: i live way north of that east grand forks
Bruce: You bet! I have talked quite a bit with Kurt Fischbeck and Paul Taylor about this as well as my neurologist.
shamar1228: yes to all n have back problems on top
Bruce: When I was young we lived outdoors ... hunting, camping and fishing. 35 below with a wind chill of minus 70 only slowed us down ... it sure didn't stop us.
shamar1228: know what u mean still try put gets hard
Bruce: Todd, there is some talk about doing some testing on the sensory issues since none have been documented before in a formal manner. I feel it is important.
ToddAllen: When my wisdom teeth were pulled 3 years ago a nerve to my tongue was bruised resulting in numerous odd chronic sensory effects, numbness, pain and even odd blasts of intense taste sensations, especially salt.
Bruce: Interesting!
shamar1228: did lips go numb
Bruce: Morning all
ToddAllen: I also have chronic numbness in the outer fingers of my left hand and in my left heel. Both seemed triggered by minor injuries.
Bruce: My numbness is the ankles and feet including the toes and also a little in the hands
Bruce: Morning Stan
Stan: Good morning
Bruce: We were just discussing sensory problems we are experiencing ... numbness in certain areas.
shamar1228: mine is left hand and right foot outside
ToddAllen: My lips aren't numb but they are weak and sensation is somewhat reduced.
Bruce: Dr. Taylor has discussed this quite a bit in past chats
Stan: I get numbness in my feet. Nowhere else yet.
ToddAllen: When I get chilled, dysfunction becomes far more pronounced. During long bicycle rides in cold weather I even lose the ability to speak.
poohsdaddy: Good Morning All from WI
Bruce: It is more difficult to stand when the sensations aren't there (in the feet)
Michael17860: Hi All
gary_kc: Good morning. This is Gary joined from Kansas City. Sprint has come here. It is about 50 degree this morning.
shamar1228: my face goes numb like cant smoke cig right cuz lips won't form
Bruce: When my hands become cold, they become clubs and are worthless
Bruce: Morning Gary and Michael
gary_kc: Hi Bruce.
poohsdaddy: Have very cold feet this morning, but doing ok
shamar1228: gary where at in kc i use to live there
Bruce: Paul Taylor should be joining us shortly. He tested the connection yesterday and it worked.
Ron: Good morning from Penna. Starting to warm up. Hooray for that.
Bruce: Spring is in the air
shamar1228: my warm is 35 rite now
poohsdaddy: Missed 3/07, but read transcript earlier. Interesting to hear from Dr. FFishbeck.
Bruce: Yes, Kurt is always an excellent guest. He is also very supportive of the KDA.
Dart!: Good morning Folks - I was caught up in reading the comments. Interesting! I appreciate being with Y'all!
Bruce: Good to have you here Dart
Ron: Glad you could make it.
Bruce: Well, I am going offline and see if I can reach Dr. Taylor.
gary_kc: shamar, I live in Overland Park where is 20 miles south of the city.
Dart!: Thanks Bruce - Everybody needs Somebody!!
shamar1228: know where it is i cleaned air ducts there many times
murf: morning
Ron: Hi Murf.
Bruce: Morning Murray
poohsdaddy: Had a spring teaser of near 75, but back down to mid 30's today. Brrr.....
shamar1228: 75 we got 49 high
murf: 62 in Houston
Bruce: We were having a discussion earlier about sensory problems ... numbness. Are any of you (the later joiners) having issues with numbness?
shamar1228: 35 grand forks
murf: ya feet
Bruce: I haven't been able to reach Dr. Taylor yet. I will keep on trying.
murf: but I'm in a chair 90% of my day
dsproul: Hi There!
poohsdaddy: Any news yet on the next conference (2009) /
Bruce: Morning Paul, thanks for joining us this morning
Paul Taylor: hello all!
shamar1228: hello
Paul Taylor: my pleasure
Bruce: I would like to welcome ... J. Paul Taylor, MD, PhD, Associate Member, Department of Developmental Neurobiology, St. Jude Medical Center, Memphis
murf: morning
Ron: Whats new with KD Dr. Paul?
poohsdaddy: More weakness in legs with colder weather...and pain in lower back.
Paul Taylor: some new work is starting to cme out...
ToddAllen: Welcome Dr. Taylor!
dsproul: Good news, I hope.
poohsdaddy: Thanks for joining our chat!
Paul Taylor: some of you were at the KDA meeting in Baltimore I think
Ron: Newe work--in what way NEW?
shamar1228: me to poohsdaddy
ToddAllen: Dr. Taylor, do you expect the work on induced autophagy to lead to therapy?
Paul Taylor: at that meeting I described the direction of our research and how we are focusing on a particular aspect of androgen receptor (AR) function
dsproul: Is that anything an 82 year old can try?
Paul Taylor: 2 papers were recently published indicatng that other scientists are finding the same thing. Specifically, that the mutant form of AR is altering the ways genes are turned on
Ron: Do you think that stem cell research will give us more of a chance for finding a cure?
Paul Taylor: I see questions about several different approaches to therapy and let me address them one at a time
poohsdaddy: Does age make much difference--or is it relative to onset and diaagnosis?
Paul Taylor: First, autophagy. Yes, I think this is a promising avenue for KD, but not in the immediate future.
Ron: What is autophagy?
Paul Taylor: Several different autophagy inducers are indeveloment but there are no clinical trials underway yet
dsproul: MY future is now.:(
loshimo11: Good morning everyone. This is Luis Shimomura checking in from San Francisco.
shamar1228: mornin
Bruce: Morning Luis
poohsdaddy: We all seem anxiuos for almost anything that may help...
ToddAllen: poohsdaddy, SBMA is progressive so age does make a difference. However, there seems to be fairly wide variation in age of onset and rate of progression which issomewhat correlated to the size of your CAG repeat count as found by the genetic test for SBMA.
Paul Taylor: Autophagy is a cell process for degrading things inside the cell that are unwanted. Like clumps of toxic AR for example. It is a natural process, but the idea is to boost it with an autophagy inducer. This has been shown to work for a number of diseases using animal models (including KD)
Paul Taylor: The second approach mentioned is stem cells.
murf: I can't see a cure in my lifetime that will affect me. If one comes ... Fantastic but your future is what you make of it. Please remember people ... life is short make the most of your time
Ron: Right on Murf.
shamar1228: how often should we get repeat counts tests
Paul Taylor: there will be a big boost in stem cell research now that the ban on federal funding has been lifted. And I anticipate that we will begin seeing application of stem cell therapy for some diseases (like diabetes and hemophelia) in the near future
Bruce: Shamar, it is my understanding that the CAG count doesn't change.
shamar1228: murf is right on the money
Paul Taylor: no need to recheck repeat count
shamar1228: ok thank you
ToddAllen: Dr. Taylor, what are the current limitations on the induced autophagy in animal models? Are there approaches (of even limited effect) that don't have negative side effects?
murf: I live alone and i'm first in line to be studied. I do it for the kids
Bruce: Paul, we were just discussing sensory issues with people with KD. Numbness in the feet/toes, hands, face, etc. It seems to be pretty common, but little has been documented on it. I know in past chats you have discussed this issue. Is it more to do with nerves not sending signals or something else?
Dart!: Murf, that is excellent advice - you are a great philosopher!!
Paul Taylor: the first generation of autophagy inducers were all based on a single target (called TOR, by the way) and in animals autophagy can be successfully induced without adverse effects that we are aware of.
Paul Taylor: But there are theoretical concerns
Paul Taylor: specifically, that these drugs also produce immune suppression
ToddAllen: Dr. Taylor, why do you think the results on the trials of androgen blockers, dutasteride, etc., have been so modest? Could these be augmented by a weak autphagy inducer?
shamar1228: my spams get so bad in chest cant breath or move is that normal
Paul Taylor: this is not a problem in animal trials in the short term because they are on the drug for about 6 mnths
Paul Taylor: he concern is that humans with KD or similar disease would need long term therapy
Paul Taylor: so a second generation of drugs has been developed that work differently
Paul Taylor: use of the second generation drugs in animals is limited so far
Paul Taylor: my colleagues at Penn applied to perform a clinical trialof an autophagy inducer (first gen) in humans with Parkinsons disease, but were turned down because it was felt that there was not enough animal data yet
ToddAllen: Shamar, I went through a period of intense disabling spasms in my mid 30s when I was more physically fit and active. In general they hit me in the evening on days when I pushed hard. They have largely subsided, probably because I can rarely exert myself to the levels I used too... But I still get wicked cramps on occaision. Both the spasms and cramps were fairly short in duration, a few minutes, but could recur frequently over a period of a few hours.
Paul Taylor: ok, back to stem cells for a sec...
murf: trying to get TJ logged in
Paul Taylor: we dream of treating neurological diseases with stem cells, and some investigators have successfully turned stem cells into neurons, even motor neurons, but delivering them to the right location os the difficult part.
Paul Taylor: there is active work on this, but I see that as a tough obstacle
Paul Taylor: the third approach is targeting AR directly and specifically
Paul Taylor: this would only apply to KD
Paul Taylor: that is the idea behind the dutasteride and lupron trials.
shamar1228: toddallen,sounds right i work hard labor etc... dont know anything else to do get urked alot
Ron: We will try anything, Right Murf--we are your guinea pigs.
Paul Taylor: I don't know of any news about those trials and the last I heard was at the KD meeting in Baltimore when Kurt gave his update
dsproul: I would lobby for aggresive testing on humans---me--long term effects I don't have the time to worry about. It seems to me that this is an opportunity for researchers to take a leap forward.
shamar1228: i try anything also
Paul Taylor: I will say that I believe that the most promising approach will be targeting AR directly
Bruce: What are you working on right now, Paul?
Paul Taylor: And this is supported by the 2 papers just published - one by Dr. Kato in Japan and another by Diane Merry at Jefferson
poohsdaddy: Ditto-- It gets very frustrating when I can't do things.
Paul Taylor: We will have a paper on this soon too.
Paul Taylor: Many of you know that we use a fruit fly model of KD.
Paul Taylor: We have used this model to examine over a dozen different parts of the AR protein to find out which ones are responsible for driving neurodegeneration.
ToddAllen: Shamar, I think your hard physical exertions are generally positive and will slow muscle atrophy, but you will need to be increasingly cautious to avoid injury. I have found that moderate injuries that bruise nerves can be exceedingly slow to heal and leave me with chronic numbness, pain and greatly acceleratred muscle atrophy of the injured parts.
Paul Taylor: We have taken over a dozen different forms of AR (each with a targeted mutation that we introduced) and made transgenic flies
Michael17860: D. Taylor did you here of Goserelin trial in Thialand?
shamar1228: thank you toddallen i try put as of late my legs are way more unsure like they drunk
Paul Taylor: Hard physical exertions can be counterproductive in KD. ToddAllen is correct about the slow recovery. I always advocate stretching and moderate exercise with my patients.
Bruce: Paul must have been kicked off line
shamar1228: that sucks
poohsdaddy: That sounds like what I have been trying to do since diagnosed.
Paul Taylor: sorry about that
Paul Taylor: to tidy up where I left off on our research
ToddAllen: Dr. Taylor, have there been any breakthroughs on any of the other trinucleotide diseases, especially the 9 other known polyQ, that are relevant to SBMA?
Paul Taylor: we have identified 3 targets in the AR protein that are involved in causing the toxicity.
shamar1228: me too but suffer when i don't take it easy i'm a farm kid so hard work is all i know
Paul Taylor: yes, there have been advances insofar as researchers working on SCA1 and SCA7 are finding the same thing as we are in their respective disease proteins
dsproul: There seems to be an increasing body of KD knowledge but no application. maybe It's time to take the Wright Bros. approach and put it into the air. Learn faster by mistakes.
shamar1228: so i got brothers what is their chances of getin kd
Paul Taylor: inall of these disease, the final common pathway appears to be the way the diseae protein influnces the process by which genes are turned on and off - called transcription
Paul Taylor: I hear you dsprou...if only there was a way to do that
Michael17860: Dr. Taylor did you here anything on the drug Goserelin trial in Thialand?
Paul Taylor: so...we believe that we have found a critical target and to prove it we are now testing this in a mouse model
Paul Taylor: Michael. I have heard of Goserelin, but nothing about application to KD. Is this published?
ToddAllen: Shamar, each of your brothers by the same mother has a 50/50 chance of having KD at birth.
Michael17860: ITs in the NIH trial listing for KD.
Stan: I'd say the odds of your brothers getting KD is pretty good Shamar. All three of my younger brothers have it.
Paul Taylor: I will look into it
Michael17860: Thank You.
Paul Taylor: Yo, hold on.
shamar1228: so they should get tested then
Paul Taylor: Shamar, you cangive me a call about this.
poohsdaddy: Since KDA has a conference each year, maybe some of the doctors and researchers could also get together to compare and discuss their findings.
dsproul: It would seem human trials are the most productive in advancing aa effective therapy. So why hold back when there are older vollinteers
dsproul: ?
Paul Taylor: a human trial is a very big deal. let me tell yu why we approch this with caution...
Bruce: The KDA conference has a session just for that. Also, every other year the Gordon Conference takes place to discuss triple repeat disorders including KD.
murf: poohsdaddy we provide a form for them to do that on the last day of the conference
ToddAllen: Shamar, how old are they? If they are within a few years of you then you ought to be able to determine who likely has it or not through comparison to your own symptoms/progression. I think looking for bulbar symptoms, especially involvement of the lips and tongue, tends to be a good indicator as it is fairly consistent and early in the disease.
Paul Taylor: first, you need to have a promising therapy, meaning preclinical evidence that it will probably work and also evidence that it will probably not be toxic to the subjects
shamar1228: how do i give you a call paul?
shamar1228: they 23 and 21 way younger
shamar1228: what about sister
Paul Taylor: Let me say at this point, as a clinical neurogeneticist, that I do NOT advocate diagnosis and clinical advice being spread over the internet in a haphazard fashion
poohsdaddy: Murf--GREAT! My brothers and three nephews all tested negative for KD some time ago.
murf: shamar1228 there is a very good chat on our website
Paul Taylor: please call my office next week 901-595-2144
murf: shamar1228 chart
shamar1228: thank you i will
Stan: Sisters are usually carriers. My sister is and so are my nieces, as well as my daughters. I understand this varies from family to family
murf: poohsdaddy right on bless their souls
shamar1228: murf chart ?
Paul Taylor: back to the trials...there are risks involved. Beyond the obvious concern about risk to the subjects (e.g. dangerous side effects) there are risks that a poorly run trial can kill a promising therapy
ToddAllen: Shamar, my first indication of SBMA was difficulty blowing up balloons which I noticed around 18 years of age. I also had facial tics, especially around the lips and eyes at that age. Your brothers might want to avoid formal testing at least through any procedures that will end up on their medical records as it may adversely affect their ability to obtain medical insurance or cover therapy if/when it becomes available.
murf: right there is a chart on how the X & Y chrom goes through a fanily
Bruce: I would recommend to anyone that has concerns about their siblings and children to discuss these issues with a genetics counselor.
murf: family
dsproul: Shamar, be careful, testing positive may affect employment chances of younger men
Paul Taylor: there are also opportunity risks to a clinical trial since it is only practical to run so many and we must make the most of these limited chances
Paul Taylor: OK, reagrding clinical testing and such...
Paul Taylor: I echo Bruce on this.
Paul Taylor: There are individuals who have the expertise to help guide you through the landmines on this.
shamar1228: i will tell them to do thank you
Paul Taylor: Some of these land mines have been mentioned here, including implications for health insurance.
shamar1228: what about social security
Bruce: Shamar, your neurologist can help you find one in your area. If none is available, the NIH has some reseources that might be able to help.
Paul Taylor: but there are other issues as well and we like to approach this on a cse by case basis so individuals can make an informed decision regarding getting testing
Bruce: Shamar, what about social security? What is your question?
Paul Taylor: Bruce is correct. Also you can email my at This email address is being protected from spambots. You need JavaScript enabled to view it. if you get stuck and have difficulty locating a professional
shamar1228: is it hard to get
Paul Taylor: Let me add that there is some misinformation included in the comments above
shamar1228: my dr put me to 25 hours of work
Bruce: Shamar, please check out the KDA website. There is a guide for applying for social security-disability that has been very helpful to many.
ToddAllen: Dr. Taylor is correct, that self diagnosis is not perfectly reliable, but it is possible. But considering there is currently no approved therapy for the disease there isn't a great benefit in being 100% sure at this point whether they have the disease or not. I correctly diagnosed myself 20 years ago and even with the genetic confirmation I still don't know if my symptoms are purely KD or if there is/are other complicating factors.
Michael17860: shamar depends on your documantation
Bruce: Paul, what misinformation?
Paul Taylor: I was not able to follow line by line while I was typing, but the comment about sisters in incorrect
poohsdaddy: My application for Social Security Disability was approved, but no Medicare or health insurance for the first two years.
shamar1228: ok thank to all imput
Stan: Then why did my sister test positive as a carrier?
Bruce: Everyone is different and it depends upon the case that you make to SS-D. I was approved for SS-D and Medicare at the same time.
shamar1228: how long it take poohsdaddy
Paul Taylor: The daughter of a man with KD is an obligate carrier. The daughter of a woman carrier of KD has a 50% chance of being a carrier.
Ron: Bruce--how old were you when approved for medicare also.
Bruce: Paul, what it your schedule like. Do you need to sign off soon?
gary_kc: Dr. Taylor, do you have home page that we can find your research?
Bruce: 57
Stan: So then it follows that both my daughters are carriers?
Paul Taylor: Men with KD have inherited this from a carrier female, so their sister has a 50% chance of being a carrier.
poohsdaddy: Was off work for six months while doing a lot of paperwork with them and doctors.
Paul Taylor: yes, and I need to run, the kids are waiting and getting a little restless right now.
Bruce: Paul, thank you so much for your involvement today and your support.
Bruce: You are a great asset to the KDA and all of us with KD
ToddAllen: All offspring of a mother carrying SBMA have a 50% chance of inheriting the mutant gene. And all daughters of men with the disease will also inherit it.
shamar1228: paul thank you
Michael17860: Thank You Dr. Taylor, Have a Great day.
Paul Taylor: You're welcome.
Stan: Thanks Dr. Taylor. I think I learned more this time than any other chat.
Paul Taylor: Bye all.
Bruce: Have a great one!
poohsdaddy: Thank You Dr. Taylor. I'm sure we are all graateful for your input!!!!!!!!
gary_kc: Thank you Dr. Taylor.
murf: thanks Paul
Bruce: Everyone, I have to run to prepare for a board meeting. Thanks for joining us today. Stay healthy and upright.
loshimo11: Thank you Dr. Taylor.
murf: stay positive men
gary_kc: Bye all.
Ron: So long guys--stay healthy till next we chat. Bye.
shamar1228: thank you see ya
poohsdaddy: Bye til next ime............
shamar1228: bye also next time guys
ToddAllen: Note, it is really incorrect to say that women are only carriers. They are affected by KD but just to a much lesser degree than males in most cases. In general women are affected so little as to be unaware that they are affected at all, but some are profoundly affected such as my mother - who also had elevated testosterone levels...
shamar1228: oic thank you
ToddAllen: Good luck to you shamar. Bye.
shamar1228: and to you