Kennedy's Disease Association

A Public Benefit, Non-Profit Organization

"The site is essential for a source for the general public, whenever one encounters the diagnosis of Kennedy's Disease and has no idea what that might be."

Archives - 2015 and Older Transcripts

Kennedy's Disease Chat Transcript  08-01-2009

Topic:  Special Guest - Dr. Andrew Lieberman

Host: Bruce Gaughran


BEGIN CHAT

Bruce: Morning
poohsdaddy: Ready or not, Good Morning. Hope we're not alone today..
Bruce: I believe we should have a good turnout with Dr. Lieberman as the guest.
Bruce: Morning Ute
poohsdaddy: Looks like murf went to sleep.
Bruce: Ute is Rick, right?
UTE: Good Morning Bruce, Pooh
UTE: That's right, Rick!
poohsdaddy: And pooh is Jeff. Good Morning UTE.
Bruce: We need a score card to help remember who is who
poohsdaddy: LIght rain and 60-ish here today... Promises of sunshine later on.
Bruce: Rick, do you have any seven year olds driving around the neighborhood?
UTE: It's hard to believe the summers half over...it'll be around 95 here
Bruce: We will be in the low 90s today and all next week. It is the dog-days of August.
UTE: The kid was quite a character... too many driving video games
Bruce: Morning Semipro
poohsdaddy: My eldest grandson is already talking about a car at 14.
Bruce: We have Rick, Jeff and myself on so far.
Bruce: The boy's punishment was four days without TV or video games.
UTE: Semipro how's the weather where your at?
poohsdaddy: I usually try to get here early, cuz my computer is old and slow (just like me).
Bruce: Even though it is summer, I am surprised more people are not on.
poohsdaddy: Do we have a guest coming today?
UTE: Actually that boy drive alot better than alot of Utahns
Bruce: I don't understand how he could use the foot peddles and still see over the dash
poohsdaddy: Good question.
Bruce: Semipro didn't like us very much I guess
Bruce: Morning loshimo11
Bruce: Jeff and Rick are also on with us
loshimo11: Good Morning Everyone!!! This is Luis Shimomura joining in from a rather overcast San Francisco.
Bruce: Our neighbors were in San Francisco this week and are heading home now.
Bruce: Mornng Mike
UTE: I see Dr Lieberman was testing the chat room last Tuesday??
MikeG: Morning Bruce
loshimo11: Bruce... Hope they had a nice time.
Bruce: There were enjoying themselves as of Thursday and were heading for Napa Valley on Friday.
MikeG: that's a beautiful area
Bruce: San Francisco is one of my favorite places ... many fond memories there
MikeG: me2
poohsdaddy: My cousin had surgery for hydrocephalus earlier this month. He did not indiccate whether it was related to KD, but I hope to talk to him soon.
Bruce: What is hydro....
loshimo11: Bruce... Wheater outside San Francisco is usually great during summers... anywhere between 70's and 90's.
semipro: Good morning. Computer acting up.
Bruce: Sorry to hear that Semipro Where are you located?
semipro: Tampa, FL
Bruce: Good Morning Andy
Lieberman: Hi. It's great to be here.
MikeG: that bay can get pretty cold if you're sailing on it... :)
poohsdaddy: It's water on the brain... they inserted a tube to relieve the pressure; and help to restore balance,etc.
MikeG: Morning Andy
Lieberman: Morning.
Bruce: I would like to welcome Andrew Lieberman, MD, PhD, from the University of Michigan Medical School. He is also a member of our Scientific Review Board.
loshimo11: Good morning Dr.
Lieberman: Hi all.
Bruce: Andy, how is your research going these days?
UTE: Welcome Doctor
Lieberman: Very well. I wrote up a summary, and again (like last time) I'm having trouble pasting.
Bruce: Do you have a MAC?
Lieberman: yes
Bruce: Okay, you have to do something special when it is a MAC. Let me see if I can find the instructions.
Lieberman: I guess that's bad. I'll just type...at my usual not very fast speed.
Lieberman: I'm a neuropathology at Michigan and my lab has been studying Kennedy disease using a couple of model systems, including cell culture and mice. The mouse model we have was made with support from the KDA.
poohsdaddy: That's good... type as fast as most of us can read... and try to ask questions as we go along. Thanks.
Bruce: Morning Ron
Bruce: Morning Don
Ron: Good morning guys.
fl-don: HI ALL
Lieberman: Right now we'
Lieberman: oops
Bruce: Dr. Lieberman is on
Bruce: Morning Murf
fl-don: Go blue!!!!!!!!!!!!!!!!!!!!
murf: Morning
Bruce: Morning Dart
poohsdaddy: Mike... still got your #, and would like to call you this week. ok?
Lieberman: Thanks for the Michigan support. Any questions, or should I tell you about what's going on in the lab?
Dart!: G'morning All!
Bruce: Tell us what is going on at the lab please
murf: ok
poohsdaddy: Please tell us about the research.
Lieberman: Right now we're working on a couple of projects with our mice. First, we're trying to understand pathways that might alter cell function and lead to cell death because these offer potential drug targets. (Maybe I'll do this in piesces so you can read while I type.)
Ron: Andy--how is the lab research doing?
murf: ok cause I'm reading slow this morning
Lieberman: We're focused a bunch of effor ton examining a cell stress pathway called the unfolded protein response. This pathway is a means by which cells deal with misfolded proteins , and we had the idea that it might be triggered by the abnormal androgen receptor of Kennedy disease.
Lieberman: It turns out this pathway is really important in helping cells survive the stress of mutant proteins. However, if this survival mechanism fails, the unfolded protein response can cause cells to die.
Lieberman: So far, we've found that this pathway is active in our Kennedy disease mice and in muscle from some Kennedy disease patients. We're now genetically inactivating the pathway in our mice. OUr initial results are really encouraging that this will impact disease. If so, there are some small molecules we plan to try to see if we can treat mice.
Ron: Andy--why is it that some of the KD guys gain alot of weight while some like myself--tend to loose weight.
Lieberman: Ron, that's a interesting question. I'm not sure it has anything to do with the Kennedy disease mutation,but more likely reflects important differences in our physiology.
Lieberman: One other thing we've been working toward is to try to find new compounds that might be therapeutically active in our model systems.
Ron: Usually loosing weight also means losing muscle stregnth.
poohsdaddy: I've also gained weight since the NIH dutasteride study.
murf: could be the amount of ice cream intake.
Lieberman: We're collaborating with a chemical biologist at Michigan who has now screened a really large library of chemical compounds (containing ten of thousands of compounds) for small molecules that will help cells digest the mutant AR.
loshimo11: Dr. Lieberman... Sounds like you and your lab have been pretty busy!!!
UTE: Are you still also working with MSU?
Lieberman: About weight: I guess the important thing would be whether the weight change is due muscle or fat. Overall activity, metabolism and body fat stores play into how your body responds.
Bruce: Andy, when you say digest the AR, are you referring to the clumping that occurs when the AR cannot enter the nucleus for cleaning (my simple terms)?
Lieberman: Yes, we're still working the group at MSU. It's been a great collaboration to look for AR effects on muscle.
Dart!: Muscle weighs heavier than fat, and I have lost a lot of muscle, which I am wondering if it can be regained through exercise. I would REALLY like that!!
Lieberman: Bruce, that's right. There are a couple of degradation pathways that cells use to digest things. We're looking for small molecules that help cells take out the trash (sort of like my mom getting me to do it when I was a kid.)
poohsdaddy: Bruce, thanks for the simple terms. I'm still learning and trying to understand KD>
Bruce: So am I
murf: me3
Lieberman: Regaining muscle probably be a really great thing. We also have to do it in a way that helps the muscle cells talk with the motor neurons that control them. Without that connection, it may not be so helpful.
Bruce: Andy, I found this about copying and pasting, I am not certain it will help: 4. Macintosh Specific Issues Macintosh users may not be able to copy/paste text between applications using the Cmd-C and Cmd-V keyboard shortcuts. Please use the Macintosh drag & drop text feature to drag text in and out of AddonChat.
poohsdaddy: I've thought that a combination of Medication, Diet & Exercise helps with effects of KD.
Ron: A good man jusdt left us--Charles Rannels who was one of the early diagnosisees of Kennedys.
Lieberman: Sorry if my lab description was too technical. The screen for small molecules (I didn't want to call them drugs because that might imply more than they are good for) has been interesting, and has yielded a promising hit that we're test in cells. Once that
murf: ok fixed
Lieberman: oops. Once that's done, if it's still looking good, we'll go on to cells.
UTE: I'm sorry to hear about Rannels, how old was he?
Bruce: I have really seen positive results with my new exercise program. I might not have more muscle, but there is definitely definition and increased strength.
kathomp: I read an article recently about the work of Dr. Robert Beal on cyctic fibrosis. A different condition, but since he's looking for a drug that would override the gene mutation, it would seem to have applicability. Are you familiar with this?
murf: close to 90
Ron: Charles was 82.
murf: 86 I think
Lieberman: I also heard about Charles Rennels passing. I was sorry to learn the news.
murf: ok
Bruce: Charlie was 81 I believe
murf: good guy
murf: over 80
murf: he had a good long life
Lieberman: Bruce, I'm glad to hear that your excercise program is helping. It might be something that's worth sharing with the others.
Lieberman: I haven't read the article on CF that was mentioned. Sounds like something I should look up.
Bruce: I have shared it with several people and also placed it on our web site.
Lieberman: Great. Have others found excercise helpful?
kathomp: CF article is in the 4 May edition of the New Yorker.
murf: I think, for me anyway, its the motivation to get up and do it
MikeG: I have but it's hard to keep on schedule!
Bruce: I have always found exercising to be something enjoyable. Most of my life I have exercised almost every day.
MikeG: especially when you're already covered up with working...
poohsdaddy: I've read about research from the Medical College of WI being done. Their focus seems to be Parkinson's with tie to other neurological disorders.
murf: P.S. all: I am not retired on disability
Lieberman: It's an important question, and one that hasn't been answered by the scientists. Do excercise in patients, or in KD mouse models, help? You would predict it might, but I think we don't have data to know for sure. On the other hand, if it makes you feel better, it seems worth continuing without data.
UTE: At 63 I work at a planetarium for my exercise, sliding my arms across the counter while in a powerwheel chair seems to be the one part of my body I'm getting by with
MikeG: sorry to hear that Murf :(
Bruce: The NIH is considering sponsoring a clinical trial on the effects of exercise on patients with KD.
murf: don't be sorry
murf: I'm not, should have done it long ago
Lieberman: I heard/read mention of a couple of other disorders, such as CF and Parkinson disease. It's great to see that you as a group are keeping up on research that may impact KD. All of these diseases are caused by protein misfolding, so advances in any one may be broadly helpful.
kathomp: The reason I mentioned the CF article was that it mentioned possible applicability to muscular dystrophy.
Lieberman: Bruce, I didn't know that the NIH is interesting in looking at the effects of excercise. I think it's a great idea that could be one component of a natural history study, looking at the progression of disease.
Bruce: I have noticed that this last year or two, more focus has been on the cleaning process of the AR ... trying to get the nucleus to accept the mutant AR or other forms of cleaning. This appears to be a more focused step by researchers.
poohsdaddy: Many of the symptoms are similar with these conditions.
Ron: Use it or loose it.
Bruce: Morning CDH
MikeG: but sometimes we're using it and STILL lose it...
cdh17901: Good Morning - Am I to understand this chat is for everyone and not just the KD patients?
Ron: That is the normal progression of the disease.
Bruce: Yes, it is for anyone interested in KD
Lieberman: Bruce, I think you're right about the focus being on getting rid of the mutant protein. There is really good data that the mutant AR, like other aggregating proteins, cause problems for cells in a great many different ways, and it may be that there's isn't only one critical pathway leading to toxicity. Therefore, people have begun to think that rather than targeting one pathway, let's find ways to get rid of the toxic protein.
kathomp: That's what Beal is looking at -- correcting the mutated protein.
Lieberman: Mike, I imagine you're right. Excercise alone won't halt disease progression. The question is whether it can be used to slow progression.
cdh17901: Thanks. I wasn't sure because the first saturday is usually reserved for patients. My husband has KD.
Dart!: THAT sounds like a brilliant idea - get rid of the toxins!!!
Bruce: Or another question about exercise, is whether is will do no harm is done properly thus giving you more strength.
MikeG: Andy, do you have any of the compounds that look promising enough to put to a mouse trial yet?
Bruce: The first and third Saturdays are for anyone interested in KD. The second Saturday is for wives, caregivers, significant others, etc.
Lieberman: Well, we have one compound that we're thinking very seriously about trying in a mouse. We have a few additional experiments to do in cells first.
MikeG: this seems like a better approach than trying to prevent the AR from going into the cell...
poohsdaddy: Any projected time frame? for the experiments... and research?
cdh17901: Great! My husband is currently in a nursing home for rehab from a hospital stay. The Physical Therapists keep wanting him to work out with weights. I was wondering if this would be more harmful to him than beneficial?
Bruce: Everyone, we were quite pleased this year that when we sent our requests for Letters of Intent of our KD research grants that we had eight respondants of which six were from foreign countries. Normally we receive 2-3 responses. To me this shows increased interest in KD research.
Lieberman: There a several big challenges in going from cells in a Petri dish to treating a mouse. We have to find a non-toxic dose, we need to make sure it gets to the places we want (spinal cord and muscle) and that it isn't broken down really fast. We're just starting to look into this.
MikeG: now we just need to get our fundraising fired up so we can fund them...
Bruce: CDH, I can send you the exercise guide that the physical therapist developed for me. It has been very good. Send me your email address (This email address is being protected from spambots. You need JavaScript enabled to view it.) and I will send it to you. It might be of benefit for a PT who is not familiar with KD.
Bruce: The address is This email address is being protected from spambots. You need JavaScript enabled to view it.
Lieberman: You did have a great response from the research community this year. I think that the number of applications, the diversity of places they're coming from, and the strength of the science is really impressive. Youall should feel very pleased with that.
Bruce: And thanks to the Scientific Review Board for thier continued support of our grant program.
cdh17901: Bruce, I have already provided it to them. Thank you.
Lieberman: Bruce, has the KDA figured out when they will meet again, or is that still pending, depending on the economic recovery, etc.
cdh17901: That is, if it's the same exercise guide as the one on the KDA website.
Bruce: Yes, it is purely an economic question right now.
UTE: Dr Lib
Lieberman: Makes sense. I have to say that your meeting is one of my favorites. I very much enjoy talking with you and seeing the other researchers.
poohsdaddy: The one thing I've found important with the exercises is to keep a record of progress/digression.
poohsdaddy: And to keep challenging myself to do a bit more each time.
MikeG: that's a good idea
Bruce: It was difficult to not have a conference this year, but based upon donations and responses from our associates, it was the right move to make.
MikeG: BTY, if anyone here would like to volunteer to help with fundraising ideas - I'm ready to listen!
cdh17901: I'm hopeful that I will be able to attend a future conference and I hope it will be close to Michigan again.
Lieberman: Bruce, I think that was the right choice. I know many private organizations, including some very large ones, have had a hard time this past year. Let's hope this most difficult times are behind us.
UTE: Dr Lieberman...do you know what city the Neurologist will have their next convention TYPE MEETING in and do you know Dr Mark Bromberg that use to be at the u OF m
cdh17901: I'm already on the Fundraising Committee.
MikeG: great!
cdh17901: Glad to help!
MikeG: we need some activity
Bruce: Andy, we are also hearing a lot about the potential benefits of IFG-1 (for muscles). Have you had any experience with that?
Lieberman: I don't know Mark Bromberg. As for the next neuroscience meeting, I'm not sure of that. This fall is Chicaogo; I'm not sure about next year.
Ron: Fundraising committee for what organization?
Bruce: IGF-1
cdh17901: KDA Fundraising Committee
Bruce: IGH-1 (I am confused ... sorry)
MikeG: is that the heat shock?
Ron: CDH--when was your husband diagnosed?
Lieberman: There's some really interesting data from Kurt Fischbeck's lab showing that IGF-1 produced in muscle can have a very good effect in KD mice. We've found that there are a several growth factors which are normally produced by muscle, that support motor neurons, whose production in decreased in KD mice. This idea makes us think that disease in muscle plays an important part in KD.
Bruce: No, but I might be suffering from heat shock the way I have been typing
MikeG: :)
Bruce: And not just the motor neurons?
cdh17901: 1989 or 1990 - Originally with Kugelber-Wielander then more recently with KD. He and his brothers all have it and his sister is a carrier.
Ron: Thanks.
cdh17901: sorry, Kugelberg-Wielander (spelling)
Lieberman: IGF-1 is insulin like growth factor 1. It's not insulin, but a cousin. It's can be made by muscle, nerve and other cells. We found that IGF-1 and other growth factors normally made by healthy muscle aren't made to the same extent by mouse KD muscle. And now Kurt Fischbeck's lab has some data showing that muscle over-production of IGF1 can help KD mice.
Bruce: I still find it wonderful that labs are sharing information and models. This is a huge benefit for researchers.
Lieberman: We like the idea that disease mucle isn't supporting motor neurons to the full extent, and in this way contribute to the disease. That's a hypothesis we're working very hard to test.
Bruce: I assume that is difficult to test in a mouse with KD
poohsdaddy: Thanks to all for coming today... Gotta go. Best to all. Bye.
Ron: Stay healthy.
kathomp: So how would IGF-1 actually be used to treat Kennedy's?
Lieberman: A lot of us who work on KD in the United States trained together or at least worked in Kurt Fischbeck's lab at one time. I guess it's an extended family, in a way.
Bruce: We are fortunate to have that extended family. My nuerologist's partner trained under Kurt at the U of PA
Lieberman: Right now, the IGF-1 study is a proof of concept. That is, a growth factor delivered by muscle, might have a therapeutic effect.
cdh17901: Dr. Lieberman, do you still work out of University of Michigan? It's not far from where we live.
Lieberman: Yes, we live in Ann Arbor and I'm at UM. We really like living in Michigan.
Lieberman: Any other questions before time expires?
UTE: Speaking of family, how is Dr Kennedy doing?
Bruce: Andy, do you know John Sladky at Emory?
cdh17901: We love Michigan too!
kathomp: How can we keep up with your research, and what would be the best way to contact you?
Lieberman: I don't know John Sladky, and the only time I've met Dr. Kennedy was at a KDA meeting. I really enjoyed that.
Bruce: Andy, thank you so much for taking the time to join us today. And, thank you for all your efforts to help us.
cdh17901: My question as well, how to contact you etc. Thank you Dr. Lieberman for participating in the chat.
MikeG: gotta run... thanks for sharing that great info, Andy. We really appreciate you!!!
loshimo11: Well... I gotta go. Thank you Dr. Lieberman for your time and updates. Everyone else, stay healthy and upright!!!!
Lieberman: Thanks for inviting me Bruce. You can email me at This email address is being protected from spambots. You need JavaScript enabled to view it. if you need to reach me.
Lieberman: Enjoy the rest of the summer everyone!
Bruce: Thanks to all for joining us today.
kathomp: Thank you so much!
murf: I'm falling asleep so I better go to. thank you Dr. Lieberman
UTE: CDH, what town are you in in Mich?
Ron: Good bye to all. Stay healthy till next we chat.
cdh17901: Albion. Between Jackson & Marshall.
cdh17901: Originally from the Detroit area
Bruce: If anyone has other questions, let us know and we will try to get you answers.
UTE: CDH, you must know Stan?
cdh17901: Stan is my husband.
Bruce: Semipro, how did you find the chat today?
Bruce: Take care and stay upright
UTE: You all have a great day... good to hear from Dr Lieberman... CDH I was born in Ann Arbor and grewup in the Irish Hills by Cambridge Junction and Washington LAKE
cdh17901: You have a wonderful day as well. Do you still live in this area?
UTE: I also went to Junior High in Dearborn... but i'm now in Salt Lake City
Dart!: Well, Folks, it has been a great 'chat'! Thanks a bunch. I know not where the light switch is, so had best not be the last man out!
cdh17901: Okay. Well, I guess I should log out now. Thanks for the chat!
UTE: May the orce ...light be with you
cdh17901: Thanks!
cdh17901: Bye all!
UTE: Semipro... catch you next time!