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Kennedy's Disease Chat Transcript 07-10-2004
Topic: KD Research Updaate - J. Paul Taylor, M.D. PhD.
Host: Murray Williams
Bruce: BEGIN CHAT
Terryw: Had to run around and manage water resources on property
PTaylor entered the room.
PA-Paul: HI all
Terryw: Hello Paul
LouLou: Pa Paul....How are you?
PTaylor: good morning!
Bruce: GOOD MORNING< PAUL
murf: morning Paul
Chuck entered the room.
Bruce: Paul, Welcome and thanks for joining us this morning
duane: ugh...my brother in New Mexico has had a lot of well problems. replace his pump 3 times in last 7 years
murf: Morning Chuck
PTaylor: I'm well, thank you, and happy to be here
Bruce: Good Morning, Chuck
Bruce: Everyone, Paul Taylor has joined us this morning to chat about his research and other subjects of interest. I was born in New York, but grew up in California. I moved back to the East for medical school and received an MD and PhD from Jefferson Medical College in 1995. I trained in Neurology at the University of Pennsylvania from 1995-1999 where I met Dr. Kurt Fischbeck. In 1999, I moved to the NIH to conduct research on Kennedy’s disease with Dr. Fischbeck. Last summer, I moved back to Penn to join the Neurology faculty and start a new laboratory studying Kennedy’s disease. I live with my wife and two children in Media, PA
murf: WOW good turn out today!//1
LouLou: Hey Anna Lea. How are you and Chas?
PA-Paul: Wewlcome Dr Taylor
Bruce: Sorry, I cut and did a paste and should have changed "I" to "he"
PTaylor: ty, where are you in PA Paul?
PA-Paul: Orefield just outside Allentown
Chuck: Hi to all. We are doing good. I (Anna Lea) am recovering from rotator cuff surgery but doing well thanks.
PTaylor: not too far away
murf: Dr. Taylor - Thank you for all you have done and are doing to find a cure
PA-Paul: Id be happy to help in any way I can ie donate tissue etc.
Bruce: Paul, perhaps you could briefly bring everyone up to date with your research.
PTaylor: I appreciate the kind words murf
PTaylor: yes, certainly
Michael17860 entered the room.
DenisP entered the room.
PTaylor: I lead a small team that is part of a bigger effort to understand why neurons get sick in KD...
Bruce: Good Morning, we have Dr. Taylor on with us this morning.
murf: Morning guys - Dr. Taylor is about to give us an up-date
Michael17860: Good morning to all
LouLou: Dr. Taylor--You said you are joining another facility and starting another research lab. WHERE?
DenisP1859 entered the room.
PTaylor: recent advances in the KD field, and in related fields, has recently helped KD researchers focus on some key questions...
PTaylor: My lab is at the University of PA, LouLou, in Philadelphia
LouLou: Dr Taylor. I have been experiencing less muscle control in my lower lip. This causes trouble talking and eating. I hope this is only temporary.
PTaylor: for instance, the determination that neurotoxicity of the androgen receptor is dependent on bind to its ligand (testosterone) has opened up all sorts of possibilities for therapy
Bruce: Can you give us a couple of examples of what this has opened up?
PTaylor: many of you are probably aware that there is a clinical trial underway in Japan using a drug called Lupron...
PA-Paul: Yes Yes
Bruce: Yes - most interesting
Michael17860: Dr. Taylor do you see any clinical trials comming up in the near future?
Terryw: Good Morning Denis
Terryw: Or evening for you
LouLou: Dr Taylor. Do you want to examine subjects in the office? I will be glad to come to Phila. I live in Lancaster which is about 70 miles away.
PA-Paul: Me Too
Chuck: I could also make that trip.
PTaylor: Lupron is a drug that works in the hypothalamus ( a small region in the brain) to reduce the secretion of testosterone-activating factors
Michael17860: Me three
DenisP1859: Actually it is good morning 12.30am. I'm at work and thought I would say hello from Tasmania, Australia.
murf: I can't wait for the results!!
PTaylor: I absolutely welcome you to my new clinic at Penn
Terryw: Glad you could make it
Bruce: Welcome to those 'down-under'
LouLou: Michael--Where are you from?
murf: How's the weather down under - mate?
PTaylor: Please feel free to share my patient contact number which is 215-573-0317, ask for an appointment with Dr. Taylor, Neurogenetics
LouLou: Hey Denis--So--You are the Tasmanian devil?
Bruce: Paul, has there been any published findings in the last few months on Lupron?
PTaylor: Since my clinic just opened last week, I have lots of openings
murf: WOW! what a generous offer!
PTaylor: sorry if I'm falling behind - I'm a hunt and peck type
PTaylor: no recent news about the Lupron trial..
Terryw: Paul, Would you say that in the area of research for cures/treatments for Neuromuscular diseases that progress has accelerated in the past few years?
Terryw: compared to in the past
PTaylor: i don't expect anything formal in the near future, but we should be able to get a good update in October
LouLou: How about giving us your e-mail address so we can make arrangements to see you.
DenisP1859: Reaaly appreciate your site, especially the personal profiles. I should get around to doing 1 myself soon. As far as I know there is 4 confirmed kds in Tassie (pop 450,000), myself, my bro and 2 cousins. Not too keen on tassie devils, they eat my chickens!
PTaylor: yes, Terry, things are greatly accelerating for two reasons...
Terryw: That would be great Denis, looking forward to your story.
PTaylor: the first is the availability of enormous scientific databases - the human genome sequence being the best example
PTaylor: the second is tremendous advances in technology, which permits work that was impossible before - too many to do justice too, but some examples would be engineering of animal models, the ability to perform large-scale rna or protein profiling, etc
Michael17860: LouLou have you heard of Knoebels Grove in Elysburg Pa? Well I live 2 miles away.
Terryw: I was sorry to hear that little Mattie passed away. He was a great kid.
Terryw: A true inspiration
LouLou: How are the studies coming along with the super mouse. We would all like to get the muscle building genes.
Bruce: Yes, Terry, he brought recognition to MD
PTaylor: LouLou, sorry to hear you're having trouble with your lower lip - have you had this before?
Terryw: Yahoo had a story last week on a infant with giant muscles. Paul did you see the story?
PTaylor: by supermouse, you must mean the mouse that has been engineered by gene therapy to grow big muscle?
LouLou: Michael, yes I have heard of Knoebels grove. I live in Lancaster.
Terryw: They spoke of it helping research into neuromuscular diseases possibly
PTaylor: this work has led to the approval of a human clinical trial for muscular dystrophy
PTaylor: while not directly applicable to KD, it is helping to break down technological barriers
LouLou: Dr Taylor--Normally didn't have too much trouble, but it is getting worse.
murf: Mine too Butch - Can't keep my mouth shut at night.
PTaylor: yes, the infant with giant muscles is a naturally-occurring mutation that creates a situation like the supermouse
murf: No one???
duane: Why is it taking so long to begin clinical trials in the USA when Japan has already begun their testing?
LouLou: Yes that is the mouse. Will we be able to volunteer for research guinea pigs?
murf: Pick me!
Michael17860: LouLou we should hook up for lunch some day. We can pick a place in between.
PTaylor: i was actually not happy to see that child exploited by the media, because he willl have a difficult time
Bruce: Paul, what do you believe is the most significant finding within the past year that well help KD research?
JEAN entered the room.
Bruce: Morning Jean'
murf: Morning Jean
LouLou: OK! Michael. Can do.
Bruce: What is the weather like in Belgium today?
PTaylor: i think the most significant advance is the convergence of observations from multiple researchers (including Dss. Merry, Sobue, La Spada, Takeyama, and others) that the toxicity of mutant AR requires binding to ligand
PTaylor: for two reasons...
murf: I feel I'm alive in a time of great discovery
JEAN: Hallo everybody from Belgium - Weather in Belgium Brr, Brr 12 degrees celsius, windy and raining
LouLou: Dr. Taylor. I know you are being bombarded with questions but, as you can see, we are hungry for knowledge about KD.
Bruce: Paul, just for your information, besides the U.S., we have associates on from Australia and Belgium.
duane: My co workers tell me daily, to close my mouth. Even when going down the hall in my chair. I don't even realize I'm doing it. I guess it has just started. Is this a common occurrence with KD?
murf: Duane - Me too!
PTaylor: first, it provides tremendous insight into the mechanism of the toxicity. now we need to determine what specific aspect (or consequence) of ligand binding is the critical part. is it because ligand binding induces aggregation? movement into the nucleus? fragmentation? these are key questions being addressed in my lab and others
murf: I talk too loud on speaker phone because I don't think people can hear me
JohnM: I'm still doing OK with the Open Mouth thing.
PTaylor: second, because it reveals an Achilles heel in the disease process
murf: This is all great news - science is advancing very fast
LouLou: This is why the chat is so great--I thought I was the only one having lower lip trouble.Mary Lou tells me to shut my mouth. I thought she ment shut-up. LOL
PTaylor: in addition to the Lupron approach, other pharmacologic means of altering hormone signalling may be of benefit
Chuck: I too have the mouth problem and have had for sometime.
murf: This is the Bulbar part of KD
LouLou: Thanks doc. we can
Bruce: When you mention an Anchilles heel in the disease process, do you mean a vulnerability that could be exploited?
PTaylor: yes, Bruce...
LouLou: Sorry--Thanks doc. We will get in touch.
duane: So its possible other drug treatments may be available besides Lupron?
Bruce: When I saw Kirt Fischbeck in the early 90's, he felt that we could have a treatment within the next ten years or so. What are researchers saying today about a treatment timeline?
PTaylor: Lupron was already on the shelf, so a good place to start, but if the approach of blocking the interaction of AR and ligand is successful, I envision an effort to develop selective drugs that will spare non-neurons from the testosterone deficit
murf: Would it be a good idea for us to start taking Lupron?
murf: Or wait for the study to finish?
PTaylor: treatment timeline is impossible to predict, I think its more likely to be like evolution - with long periods of no advance sprinkled with exciting periods of rapid advancement
DenisP has left the room.
DenisP1859: Time to say farewell,past my bedtime. Will read the transcripts, with interest, later. It's mid-winter here ,0 degrees C tonight. All the best everyone.
duane: I myself suffer from the "benefits" of testosterone. Do you envision a time when KD'ers will be able to take supplemental injections of Testosterone to increase strength / stamina and muscle?
PTaylor: I feel strongly that KD patients should not take Lupron off-label. It has well-documented adverse effects and no documented benefit at this time
Bruce: Take care Denis
murf: Take care Denis
LouLou: So long Denis. Stay healthy.
DenisP1859 has left the room.
PTaylor: didn't understand your question duane, are you taking testosterone now?
murf: OK Doc.
duane: sorry, no i meant the lack of testosterone
PTaylor: as everybody here is well aware, KD patients have variable amounts of testosterone resistance because the polyQ-expanded AR probably doesn't work as well as a normal receptor
Michael17860: Dr. Taylor do you think that a certian diet can be a help to KD'ers. I have noticed that when I eat steak the night before, I feel a bit stronger the next day.
FL-DON: i was on the ohio state study in the 90's taking leuprolide (lupron) and i got so weak, i had to stop taking the drug.
Bruce: Paul, I continue to read about links between Huntington's Disease and KD and that if find a treatment/cure for one will lead towards a cure for the other. What other diseases have links that research in one area could help KD research?
murf: That's not good Don
duane: My dr has prescribed Lupron, but the cost / adverse affects, in my opinion, outweigh the benefits.
Chuck: I was taking testosterone for a number of years, the results of a clinical trial lead by Dr. Mendel at Ohio State in Columbus.
PTaylor: but KD patients are not actually deficient in testosterone, just resistant to the testosterone they have.
PTaylor: who is your Dr duane?
LouLou: Great chat today. Dr. Taylor, thanks for sharing your knowledge with us. Alot of questions on various subjects. Thanks for coming on the chat.
murf: What adverse affects Duane?
PTaylor: research into other motor neuron disease like ALS (Lou Gehrig's disease) may have a direct impact on our understanding and treatment of KD
duane: heat flashes, increased breast size, overall loss of masculine characteristics.
FL-DON: my neurologist took me off of testosterone, wiich i was taking due to the ohio state study. said too dangerous
PTaylor: also, other diseases that have polyQ expansion...
duane: too dangerous
murf: I don't need any more of that !!
duane: Sharon Nations, UT Southwestern , Dallas
FL-DON: the kda site has a recommendation to stop testosterone
PTaylor: there is an exciting paper out in Nature Medicine this week shwing a gene therapy approach that was effective in a mouse model of spinocerebellar ataxia, which is related to KD
Chuck: After discussing with Dr. Rothstein (John Hopkins) and Dr. Fishbeck I was advised to stop as they decided there was no value in taking.
Bruce: Could you send me a copy of that article, Paul? We can post it on our web.
PTaylor: If Dr. Nations, or any other of your doctors for that matter, wish to discuss treatment of KD, progress in the field, anything, by all means encourage them to get in touch with me
Bruce: Thank you
duane: Can they call the number you supplied in todays chat?
FL-DON: also 2 great articles at "scientificamerican.com" on stem cell research & gene doping
PTaylor: yes, that will work. i just got a new direct number yesterday, but can't remember it, lol
PTaylor: i can send it to you MOnday
Bruce: Thanks, Paul
duane: Dr Nations treats primarily ALS patients. I'm the only KD'er she has , that I'm aware of. However, UTSW Dallas is making headway in ALS research.
PTaylor: yes, I have a collaborator there named Jeff Elliott, have you seen him?
Bruce: Paul, as you can see, we are all starving for information on KD research. That is why we really appreciate you taking the time to join us today.
duane: He was the dr I saw last time i was there. great guy.
PTaylor: feels like Ihaven't had time to duscuss our work too much, sorry
PA-Paul: Dr Taylor I too want to thank you for joining us today It show us someone is still working toward an end SOME DAY, its just discouraging not knowing when.
Bruce: Well, if you want to take a moment and discuss your work. Please do. We'll wait.
duane: yes we're anxious for any news
murf: Yes, please hold questions for a moment
PTaylor: I'll say this briefly, we have now generated a series of transgenic Drosophila with KD. this tool fills an important niche in our field and will allow us to quickly test hypotheses developed in cell culture and pick the best experiments that should be performed in the mice. this is important because mice experiments are time-consuming and expensive
Bruce: Paul, for the uneducated, could you explain "a series of transgenic Drosphila with KD"?
PTaylor: i have established collaborations with several researchers who are working with or developing mouse models, including Drs. La Spada, Ellerby and Lieberman (and I am open to collaboration with anyone) to test out ideas that may then be passed back for mouse experiments.
PTaylor: transgenic Drosophila is a lot simpler than it sounds...
PTaylor: we have introduced the human androgen receptor into fruitfly...
Bruce: It appears the level of collaboration is increasing dramatically. We really appreciate that.
PTaylor: some have normal polyQ lengths like 12-19 and they are healthy
PTaylor: others have expanded polyQ like 50-120 and they are not so healthy...
PTaylor: in fact, they develop neurodegeneration when they are fed testosterone
PTaylor: yes, most people in the KD field are particularly committed and collaborative
Bruce: Testosterone isn't the poison. It is what our genes do with the testoterone that makes it bad. Is that correct.
PTaylor: that is correct, testosterone doesn't bother normal flies...
PA-Paul: is poly-Q lengths the same as CGA repeats
PTaylor: nor does it bother flies that have the nornal AR gene
PTaylor: the other interesting thing is that flies with the expanded polyQ gene are just fine if not fed testosterone...
Terryw: Paul did you read on that Myostatin
Terryw: and that infat muscle growth
PTaylor: but something happens when the testosterone interacts with the expanded gene...
FL-DON has left the room.
duane: is there a correlation between the number of CGA repeats and the degree of severity of KD symptoms?
LouLou: Doc--most of your colleagues are committed to research--All of the KD'ers should be committed. LOL
PTaylor: finding out exactly what that "something" is is the crusial question
murf: Please continue chatting - no time limit
PTaylor: yes Duane, there is a rough correlation between CAG repeat length and disease onset and severity - although not as strong an association as seen in some other CAG diseases like Huntington's
Bruce: Paul, I know I promised to release you at 11:30. I really appreciate you coming on to chat with us today. We also appreciate all of you and your team's work in trying to find a treatment or cure. Are you able to stay on a few minutes longer?
PTaylor: yes, Terry, i saw that work and know those investigators
PTaylor: i can stay a few minutes
Terryw: seems interesting
Bruce: Thank you. When you have to go, just let us know.
Chuck has left the room.
stevefu64 entered the room.
PTaylor: yes, we were discussing that earlier. Bruce, do you have the comments I sent you about that, maybe you could pass them on?
JohnM has left the room.
Bruce: Yes, I have them and actually sent them to the BOD. We'll post them this coming week.
Bruce: Thanks for responding to that article. It helps explain things.
PTaylor: about the work by Lee Sweeney
Bruce: Any other questions for Paul this morning?
stevefu64: just got up sorry fellows i missed out
stevefu64: whos paul???
Terryw: sorry stevefu64
PTaylor: let me thank you all for inviting me to chat today. I've enjoyed it and would be happy to come back in the future
duane: Dr Paul, I've mentioned my interest to Dr Elliot in participating in US clinical trials. He stated that I would be included because I have KD.
murf: I just want to say thank you again. We appreciate all the work you have done and are doing !! Big time!!
Bruce: Thank you, Paul. We really appreciate everything you have done and are doing for us.
Terryw: Thank you Paul.
LouLou: Dr. Taylor--THANKS again. Great chatting with you.
Bruce: Paul, please give our thanks to your team also.
duane: Is there a national db of KD'er s the research team can access when selecting participants?
Michael17860: Thank You all, I must go and cut grass.
Michael17860 has left the room.
PTaylor: I also want to express my thanks to KDA for helping to support my research, that was especially crucial this year with the new lab
Bruce: This concludes the chat with Dr. Paul Taylor. Thanks to everyone for joining the chat today.
PTaylor: bye All!
duane: Thanks Dr. Taylor.
Bruce: Our pleasure. We hope we can do more in the future.
Bruce: END CHAT
PTaylor has left the room.
JEAN: Dr. Taylor - Thank you for the informations - All KD's wish you a fine week-end
murf: Bye Paul Take Care
LouLou: So long to all. Stay healthy till next chat.
Terryw: Bye all
duane: THANKS KDA...what a blessing! !