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Kennedy's Disease Chat Transcript 06-16-2007
Topic: Special Guest - Andrew Lieberman M.D. Ph.D.
Host: Bruce Gaughran
Bruce: Morning Terry and Don
doughboy: Hi, Don
Andy: Good morning.
Andy: Please call me Andy during the chat. It's lots shorter to type.
doughboy: Hi, Terry and all you other "Gentlemen"
Bruce: BEGIN CHAT
Bruce: This morning, our guest is Andrew Lieberman M.D., Ph.D. He is an Assistant Professor at the University of Michigan. Dr. Lieberman is also a member of our Scientific Review Board. Dr. Lieberman's laboratory studies inherited neurodegenerative diseases, with the goal of understanding the mechanisms underlying neurological dysfunction so as to develop effective treatments. They are particularly interested in the CAG repeat diseases, a group of nine genetically related disorders caused by expanded CAG/glutamine tracts in the coding regions of disease-causing genes. Among these disorders is Kennedy' *s Disease, a degenerative disease that predominantly affects lower motor neurons and is caused by a mutation in the androgen receptor gene. The mutant protein mis
Gary_KS entered the room.
fl-don: go blue!!!!!!!!!!!!!!!!
danwolfe: sorry I am Ohio State
Andy: Thanks for the nice introduction Bruce. Sounds like there's more than one Michigan fan here this morning.
Gary_KS: Good morning. Gary Uchiyama from Kansas City.
Bruce: The mutant protein misfolds, aggregates, and abnormally interacts with other proteins, leading to both a toxic gain-of-function and a partial loss of normal function. They have developed both a knock-in mouse model and cell culture models of Kennedy's disease. They are using these systems to understand the mechanisms by which the mutant androgen receptor causes selective neuronal dysfunction that is characteristic of this disorder."
fl-don: bruce, your writing is under the participant screen
Bruce: Morning Gary
MICH has left the room.
fl-don: dan ggggggggrrrrrrrrrrrrrrrrrrrrrrrrrr
kellyC_ entered the room.
Bruce: Morning Kelly
Butch entered the room.
kellyC_: good Morning Bruce....
Bruce: Andy, what is going on in your lab these days that is exciting?
Gopher entered the room.
Andy: Good morning everyone. As Bruce said in his intro, I’m at researcher at the University of Michigan. Much of the work in my laboratory is dedicated to studying Kennedy disease. We’re trying to understand how the mutant androgen receptor causes neuromuscular disease so that we can try to help develop effective treatment strategies.
Bruce: Morning, Golpher. Dr. Lieberman (Andy) is on with us this morning.
Butch: Good morning all. Hi Dr. Andy. How arew you?
Gopher: Good morning all
Andy: I'm great, Butch. How are you? To follow up on what we're doing in the lab...I wrote up a nice summary but it's not pasting into the chat site so it will take me a minute to type it again.
Bruce: Andy, in recent months there has been an abnormal amount of papers published on KD research. I am taking this as encouraging news for all of us with the defective gene. Even though most of the papers are focused on different areas, it appears we are making some headway in this area.
Bruce: Andy, don't worry, we'll wait.
doughboy: Dr. Andy, I read alot about what you and the other researchers are doing to research KD. I'm 51 and wondered if you actually discovered something that would help KD, would it be in time to help us or the next generation. I'm asking so I can realistically plan my future.
Andy: Bruce, I thin that's right. There's been some excite progress in many areas, from fly or mouse models up to the start of a clinical trial.
MICH entered the room.
Butch: Dr. Andy.....What can we do as an organization to help you with your research. I know we are all willing to be your guinea pigs. Use us!!!
Chuck entered the room.
mjo5712 entered the room.
Andy: So, a very important is whether there's something in the near future that might help KD patients. It's probably too early to tell with certainty, but I'm optimistic. Based on the animal models, it's become clear that testosterone is key to driving the toxicity of the mutant androgen receptor, and so anti-androgen therapy is very reasonable and is being tried by groups in the US and Japan. Studies in the animal models have suggested other potential treatment strategies and these might be useful in combination.
Bruce: There also appears to be a lot of collaboration going on between different labs. That also is positive. By the way, did you go to the Gordon Conference this year? If so, did anything interesting come out of it for people with KD?
Butch: Hi Chas and Anna Lea. How are you guys?
Chuck: We are ok - how are you and entire family??
Andy: Butch, you ask what can the KDA do. A lot is stuff you're all ready doing. I think the annual meeting that involves patients, families and investigators is wonderfully inspiring for all who attend. Also, pilot grant support is a great way to get experimental studies moving. Your support of our development of a mouse model was really important early on. And the involvement of patients in clinical trials is key.
doughboy: Andy, so are you saying we should take testosterone or we should not?
doughboy: Anybody talk to Murf this AM, it's unusal for him not to be here?
Dart! entered the room.
Bruce: Murf is signing some papers and won't be on this morning.
Andy: The Gordon Conference that Bruce referred to was a scientific meeting held last month that focused on KD and other, similar disorders (the CAG repeat diseases). It was a really wonderful chance to talk about our work with people from all over the world. The KDA was very well represented -- your financial support of the meeting was recognized and your group had a participant there.
Michael17860 entered the room.
TerryW: TJ,, I have not
MICH: Doctor, you mentioned Japan, is there a significant difference between Leuproreun and Dutasteride?
Michael17860: Hi All
Andy: Testosterone makes the disease worse in all the animal models tested so far, so there's no reason to take it.
doughboy: Andy, so is it of importance the number of CAG repeats you are diagnosed with? I was diagnosed with 61 repeats!
Bruce: Morning Dart and Michael
TerryW: TJ, Eat lots of Wheaties :)
Dart!: Humble apologies for being late - I will listen hard so as to catch up.
doughboy: Terry, do you have any way to try him? When I'm on the CPU, my phone line is tied up! I know last night he was going to be on.
Andy: Leuproleun (L) and dutasteride (D) work differently but both have the overall effect of decreasing testosterone stimulation. L is used to prevent testosterone production, whereas D effects testosterone metabollism to a more activ form.
Bruce: TJ, Murf wrote me last night and said he couldn't be on because he was signing some papers.
TerryW: let me look up his #
TerryW: oh, ok
doughboy: OK, Bruce, I'll fill in in when we meet for dinner after while!
Butch: Does that mean you will buy, TJ?
Andy: In the population, the longer the repeats, the early onset the disease. This is a general rule of thumb. It also seems that there are other factors that modify or affect onset and severity of disease, and we don''t have a good understanding of what those are. So, there are many examples where this general rule doesn't ft the individual case.
doughboy: No, hell no, Weaser is!
Butch: Poor Weaser.
TerryW: Andy can the length of the Repeats change, We had a KD individual bring this up to us.
doughboy: She luvs me
danwolfe: Andy, some of recent papers I won't mention names, involving androgen modificatin in cell and mouse models use encouraging language on treatment suggesting reversal .. is that generally current thinking
Alexandre entered the room.
Bruce: Morning Alexandre
Andy: There's evidence that the repeat number may vary slightly in different cell types in our bodies, but it's not clear how much that affects disease onset.
Butch: Dr. Andy--It is so great that you joined us today and are able to share some of your research data with us. Thanks!!
Bruce: We have Dr. Lieberman on (Andy) from the University of Michigan. Andy is also a member of our SRB.
fl-don: go blue!!!!!!!!!!
Alexandre: Good Morning to all from Brazil
Bruce: Andy, we such variability in the symptoms, onset and severity between many of our members. Do you see the same in your mouse models?
Butch: Hi Alex--glad you could join us on the chat.
doughboy: Have there been any results from our trial with the Dustdsteride?
Andy: I think we all hope that treatment with antiandrogens or some other therapy will be effective even after the onset of symptoms -- either by preventing more cells from dying or by fixing cells that are not functioning correctly. The notion that cells are still around but are sick and could be possibly rescued by thereapy is really exciting.
Bruce: That is encouragin for us older associates.
Butch: It is encouraging that there are so many of us "older" associates still around.
doughboy: I have just about given up, my arms and legs have been so sore and weak lately that I have been staying in bed alot. No energy what so ever and I've lost 30 lbs. on Nutri system in the last 90 days.
Bruce: Andy, let me try again on my earlier question. We see such variability in symptoms, year of onset, and severity between associates. Do you see this in your mouse models?
Andy: Bruce asked whether we see differences in symptoms in our mice, like is so often seen in people. There's some variability, but not as much as in people and that's because we've controlled for the main things that cause variability in people. All of our mice have the same CAG repeat length, all are housed in the same environment, eat the same food, have the same excercise options, and have the same genetic background.
doughboy: Any body else feeling like that?
Dart!: G'morning to all, and if convenient - what are the 'repeats', and how does one avoid or neutralize testosterone? Yes, that IS interesting, that ailing cells can be rejuvinated!
Michael17860: Dr. Andy, will there be any trials on ASC-J9 in the near future?
Andy: I haven't heard anything about the NIH trial results yet. I think Nick DiProspero is coming on the chat in a few weeks and it will be interesting to see what he has to say.
Butch: Yes TJ. Been having alot of trouble lately.
TerryW: Sometimes TJ
doughboy: I'm sick of it! LOL
kellyC_: How old are you...Doughboy? if u dont mind me askin the wife here is curious?
Bruce: Dart, repearts are CAG Repeats. The number of repeats in your DNA determines whether you have KD or not. Andy can do a better job of explaining this.
kellyC_: ok ty...
Butch: What about stem cell ressearch? Creating cells from tissue.
doughboy: Your Welcome Kelly
Andy: ASC-J9 is a compound identified in a lab at the University of Rochester that looks really interesting. It seems to have a very good therapeutic effect in one of the mouse models of KD, and it works seemingly differently from the antiandrogens. I think they're probably a ways away from human trials, but it's a great example of the type of compound that should get priority.
jameson411 entered the room.
Bruce: Morning James
jameson411: good morning!
doughboy: Good morning
Nick entered the room.
Bruce: Morning, Nick
Nick: Good day
Butch: WOW!!! 18 on board today. All because of you Andy.
jameson411: it seems quiet this morning
doughboy: Does KD affect the nerves, I'm asking because my arms,legs & feet tingle, hurt and go numb constantly?
Andy: Stem cell reseach is an exciting new frontier for work on neurodegeneration. It has lots of potential theoretically, but we're a long ways off from thinking about it in the clinic. As for KD research specifically, I'm not aware of labs studying stem cells in KD models. However, labs are studying it for other motor neuron diseases (eg ALS), and what we learn there would be relevant to KD.
Bruce: Jameson, read the transcript afterwards. There has been some interesting information from Dr. Lieberman.
doughboy: My feet are getting very sore to walk on, especially the bottom of the feet!
Butch: Thanks Andy.
Nick: newbie on the chat, but a long-time lurker.
danwolfe: doughboy, sounds exactly like my situation
TerryW: TJ, I you cant walk on the tops LOL
Bruce: Welcome again Nick. Please read the transcript afterwards to see what you missed.
Andy: KD definitely effects the nerves. Both the motor nerves that control your muscles and the sensory nerves are affected. It sound like the numbness you're experiencing is most like due to sensory involvement.
doughboy: So what do you do Dan?
doughboy: So what can I do about that, Dr.?
danwolfe: Bruce helped get a good response on the nerve question today on the message board...
Bruce: TJ, I found that massage helps.
doughboy: Thanks, Terry!
TerryW: Coushins TJ
Andy: One interesting thing we've found from studying our mice is that although the motor nerves are affected, we also find lots of changes in muscle quite early on. And this has led us to start testing the idea that muscle might play an important role in the disease process.
doughboy: Yes, I have been going 2 to 3 times a week for massage theraphy
Bruce: I take the time each day to exercise and massage the areas that are losing feeling. Massage seems to help and feels pretty good also.
mjo5712: what about results for the trials
doughboy: My Neurologist tells me me I'm losing muscle
Andy: Sounds like the sensory involvement is really troublesome.
Bruce: Andy, is this what you were explaining at the conference last fall?
danwolfe: My situation is I have almost 0% surface and deep sensation in the feet but pain on the soles esp when I walk. I have had elecctrodiagnostic tests run several times before find KD, but am still pursuing more diagnostic to make sure there is no other major cause of axonal degeneration
fergi entered the room.
danwolfe: I have no loss of motor function
Bruce: Morning Fergi
doughboy: It is for me because my Dr. tells me I've lost my reflexes im my feet and right wrist already
Bruce: How are things in Spain today?
doughboy: That's why I was wondering about the CAG repeat length
fergi: afternoon in Spain now
Michael17860: Dr. Andy I am taking Creatine for a few months now, and It has helped me to maintain muscle. Has there been any study on Creatine?
Nick: Anyone taking tumeric supplements?
Andy: Bruce, yes, we found that the muscle is affect really early in the course of disease in our mice, before we see any changes in the motor nerves that control muscle movement. And then our collaborators at Michigan State made a different mouse model in which the androgen receptor is over expressed only in muscle, and the mice get motor neuron diease. Our thinking is that a sick muscle might not be able to support the survival and normal function of the motor nerve cell properly and therefore contributes to the disease.
fl-don has left the room.
Butch: Interesting speculation Andy>
Bruce: Does that focus some of your research into another area then?
danwolfe: Andy, and is it also sensical that after progression of KD over exercise could accelerate the muscle deg.
MICH: Andy, glad to here my school is collaborating!
Gopher: Very interesting, Roger experienced noticable loss of muscle strength first...several years before diagnosis
Andy: Creatine has attracted attention in other disease models and so has curcumin (I assume that what's in tumeric). I don't know of data on either in KD models, and certainly there's been nothing in KD patients.
Michael17860: Nick I have started taking Tumeric, too early to see any difference.
fergi: knew a new KD in Spain. He is a Doctor in pharmacy
doughboy: Thanks to you Dr. for taking time out of your schedule to chat with us. It really helps! Everyone I have to leave, you all take care! Bruce, please try to remember to e-mail me that article, please! Goodbye all! Ya'll take care and remember the Great State of Texas just won the NBA Champiuonship, AGAIN!
Andy: We setting up some experimental systems to really test how much a role muscle pathology plays in the disease. We're doing this in a mouse model that will allow us to express the mutant androgen receptor only in nerve or only in muscle, and then we'll see how much each cell type contributes. As for excercise, I don't think it's been tested in any mouse models. It's seems like it might be a good thing to do so long as you check with your treating MD>
Butch: Just to let you guys know, I started my second year at the NIH trial research. Am glad to report that the TEAM at NIH is just as excited about the trial as they were the very first day.
Nick: Does anyone else find that the initial period of severe muscle cramping (years) fades as the muscle bulk goes down?
doughboy has left the room.
Andy: Butch, I think we're all excited to see the results of the trial.
Bruce: Andy, this sensory issue is very interesting to me. Many of us have experienced some loss early on and it increases as we become older.
Andy: Nick, my understanding is that the muscle cramping often comes before the muscle weakness. Sounds like that was your experience too.
kellyC_: Nick.I had KD now for 9 yrs now, and I have had nothin but Severe Mucles Spasm to date.. good question!
Bruce: Nick, fortunately in my case, the sever muscle cramping has deminished to almost nothing these day. That could be because I have a lot less muscle to cramp.
Chuck: Nick and all, in my case the cramping of the muscles faded away as the bulk of the muscle receded. I no longer have muscle cramps.
Butch: Sure--when we lose alot of muscle--nothing left to cramp....LOL
Dart!: Do you reckon, Dr. Andy, that supplements such as curcumin 'fill in the gaps' as to what is lacking in folks with neurological problems? Is there a supplement that will help to overcome cramping?
Nick: Good news and bad news 8-)
Alexandre: Butch what is about the NIH trial?
Bruce: I now experience deep muscle aches more often ... it almost feels like the muscle is dieing.
fergi: I agree with Bruce. When the weakness go forward, cramps desapears totally
Nick: The aches feel like they're in the bones, very deep.
Andy: The sensory involvement has not been a focus of study in the mouse models, perhaps because it's not as easy to test for. It sounds like it's an important clinical issue for many of you -- and that's one important lesson I'll take away from this morning's chat. Perhaps we need to look to see if it occurs in our mic (I suspect it does), and if so, we could try to study it to better understand it.
fergi: Befora appears weakness, cramps inme were terrififc and painfull
Michael17860: I have found that Pantothenic Acid helps with the cramping
Butch: Alex..50 guys with KD are taking a clinical trial at NIH. It is a dusteride trial. 25 guys are getting the sugar pill and 25 are getting the real deal. Results to come next year.
Gary_KS has left the room.
jameson411: Nick... I have thesame thing. Muscles, especially thigh and shoulders, ache all the time.
Gary_KS entered the room.
Bruce: Yes, we are almost 50% through the trial.
Andy: The mechanism by which curcumin might help is not absolutely clear. Curcumin seems to bind to misfolded proteins in a bunch of neurodegenerative disorders, and it may be that it's helping the cells degrade these proteins.
Nick: My neurologist suggests that some of the numbness in my hands results from leaning newly skinny arms on my elbows too much. Being aware and avoiding leaning on my elbows did seem to help a little.
jameson411: Where can i sign up for a trial.
Bruce: Cramping in some respects was easier to handle because they went away. The aches do not go away and some days the aches are pretty intense.
mjo5712: light work out has helped me with cramps
Bruce: Interesting, Nick.
jameson411: so it seems we've got to keep moving.... just keep moving :-)
Alexandre: Nice Butch, thank you for the infomation I would like to know more about this trial, can you mail me?
Nick: Is acheing universal or do some avoid it?
Andy: When have you notice the numbness and tingling in the feet? Is it early in the disease or late?
Bruce: Jameson, the trial has all the people it currently needs. We now have to wait for the results.
Butch: Jameson--the trial is full for this trial. Stay tuned for more info to come.
danwolfe: Andy, generally from what I see re more severe sensory a couple of us were talking we are talking sounds like distal focus main problem in feet but moving up the legs over time....Bruce, I also told the neurologist here that I felt like diabetic demyelinating symptoms but I am not. In thinking KD kind of synergistic interaction effects could accelrate sensory probl..
jameson411: I'm young, mobile and progressing... I think I'd be a good candidate for a trial
MICH: I'm 60 and I've never had much aching... a few cramps.. charley horses... but not very often over the years
danwolfe: I volunteer for specific sensory clincial study
Bruce: Andy, in my case it started in the 40's and has become progressively worse until today it is pretty well spread across both feet and some of the hand area.
jameson411: maybe next time
danwolfe: I now cannot walk across the room barefoot
Nick: The ticket to minimizing cramping for me was heat. Sleeping on top of my electric blanket was key. Some nights the choice was between cramping or sweating; but at least you could have a choice. Cramping much less now.
danwolfe: But I go to fitness daily and work out on the orbital cross trainer
Gopher: Heat works!!!!
danwolfe: Yes a hot bath is heaven
Andy: This NIH trial is really just an initial effort, and I think it's important to remember that we probably won't get a homerun out of it. Just as important is the fact that we've learned a lot about how to run a trial, we 'll have documented some information about the normal course of the disease, and we may have evidence that antiandrogen therapy is effective in treated patients, atleast to some degree.
jameson411: i have an electric bed warming... it is the best invention since cookies. I love it love it love it
Bruce: Reference the numbing (tingling), I just assumed that it was another result of the lack of circulation. I tested that and now do not believe that is the case.
kellyC_: Anyone with Vision problems and tension headahes.is that Kd realated to?
Butch: Andy--we don't expect miricles but we can still hope.
Gopher: sinus headaches???
kellyC_: Tension headaches
Nick: Tension headaches sounds like stress to me.
Andy: I don't think vision problems are common with KD. The stress of living with the disease is certain a reason to have tension headaches.
Bruce: Five minutes left in the formal portion of the chat. Those wanting to stay on afterwards are welcome to.
kellyC_: or Coital headaches
MICH: Do drugs like Viagra and Zocor possibly negatively affect KD and androgen and testosterone?
jameson411: Dr. Andy - is there anything that KD sufferers should NOT consume, besides testosterone of course.
Gopher: Does the phlegm and drainage come from sinus?
kellyC_: oooo ok thanks DR A
Nick: How about Cialis?
jameson411: barrage of quesitons.... :-|
danwolfe: Andy, I have tremedous admiration for your work and the others at the center of KD research. Can you mention on the atmostphere of discovery and collaboration among the groups - it seems mainoy focused in Japan and Penn / Seattle... .
Michael17860: Good question Jameson....
Butch: Well you all. I must go for now--stay healthy till next we chat...Bye!
Andy: No data on Cialis. The only thing we'll have good human data on is dutasteride from the NIH trial.
jameson411: bye Butch
Butch has left the room.
Bruce: Dart, the phlegm only becomes a problem when we can't easily clear it from our system. The choking or gagging is the result of not being able to clear it. The throat and swallowing exercises noted in the exercise guide help.
jameson411: what is dutasteride and what does the data say...
Alexandre: DR. Andy , I understand that we don't have to use testosterone?
Nick: Any sense of how much dutasteride impacts libido?
Chuck: Thanks Dr. Andy - very informative and enjoyed much.
jameson411: my understanding is testosterone will accelerate KD symptoms.... stay away!
Bruce: Andy, thank you so much for being a part of the chat today. Is there any last message you want to leave with us?
Chuck has left the room.
danwolfe: Everyone, my first chat but very helpful to hear from everyone....
Gopher: Good reminder, Bruce...we were thinking sinus problems
Bruce: Take care Dan.
jameson411: dan... how old and where from?
Andy: There a very large group in Japan study KD, and several groups in the US. Many of us trained with Dr. Fischbeck, who's now at the NIH. So the groups in Philadelphia, Seattle, and my own lab fall into that category.
Bruce: The family?
jameson411: i'm 34 and in CT
Bruce: END CHAT ... This ends the official portion of the chat. For those wanting to stay on line to chat. Please do so.END CHAT