Kennedy's Disease Association

A Public Benefit, Non-Profit Organization

"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."

Archives - 2015 and Older Transcripts

Kennedy's Disease Chat Transcript  06-21-2008

Topic:  Special Guest - Dr. Andrew Lieberman

Host: Bruce Gaughran


liebermn : Thanks for inviting me to participate in the chat. Do you have any questions.
Bruce : "Today we welcome Dr. Andrew (Andy) Lieberman, from the University of Michigan. His topic today is Research Update & general KD Questions"
Bruce : "Andy, what is the latest goings on in research from your lab?"
liebermn : "Bruce, I wrote up a long paragraph telling you all about some stuff, and I'm having trouble pasting it from my word doc."
Bruce : Cut it into smaller pieces and try that.
FL-DON : "bruce, sunny in mid 80s"""
mgshidler : dr liebermn i would like to know if all kd patients are affected bilaterlly
Ron : Hi Andy. I have been having alot of trouble with tendonitis. As you know we guys with KD have to use our arms and legs to rise from a chair. Especially a low chair.
liebermn : "No, that's not working. It won't let me paste."
TerryW : iit should let me check some settings
Bruce : I am sorry to hear that.
Alexandre : "Dr. Lieberman, what can you tell us about the recent researches? "
liebermn : "I think KD usually presents bilaterally, but there are probably instances when one side is worse than the other."
poohsdaddy : That's for sure--more effort to do less than before KD
liebermn : "Sorry to hear about your tendenitis, Ron. I'll try to summarize what new in the lab."
poohsdaddy : My left side is more painful with more weakness on right
mgshidler : my right side is weaker but tremors are greater on the left
liebermn : "Ah. Great to see a Michigan fan is here. So, we've recently started a collaboration with a chemical biologist at Michigan to look for new therapeutic compounds. "
poohsdaddy : Is research in MI similar to that at NIH?
KellyC. : first time yesterday my legs gave me severe problem?? felt like they were on fire? and really
Bruce : This is a test of the pasting capability from WORD into Chat.
Bruce : "Andy, I just tried to cut and past from Word and it seems to work. I use the control V for the paste."
MikeG : Andy - I had the same problem using the mouse to paste... try using the Ctrl-V key.
UTE : Are you still collaborating with my alma mater MSU?
liebermn : Our strategy is to find small molecules that activvate the cell's own protein quality control pathways. (Control V didn't work on my Mac.)
TerryW : Andy try it now
TerryW : You may have to log out and back in
TerryW : I think you will have to logout and back in
TerryW : I added you to the special guest group
poohsdaddy : It's great to see more participants this morning.
liebermn : "Okay, I'll be back in a minute."
Alexandre : "Dr. Leieberman, what can you tell us about treatment with stem cells?"
TerryW : he willbe back in 1 min
mgshidler : i have great success using creatine monohydrate and nictic oxide stimulator. has anyone else tried this combination?
Bruce : Wait one minute for Andy to log back on and then ask the question again.
Bruce : "No, MG, I don't know anything about it. What kind of success?"
carofer : mgshidler... where do you get this concoction?
mgshidler : GNC
Michael17860 : what is nictic oxide stimulator and where can you get it.
Bruce : Welcome back Andy
TerryW : you are green now
liebermn : Thanks!
liebermn : Still can't paste. Oh well.
TerryW : it is set to let you paste 2048 char in the room at a time
mgshidler : "success would be less muscle cramps, strength and longevity. nitric oxide is a blood vessel dialotor and relaxor. get it at otc at general nutrrition centers"
poohsdaddy : Tell us more about your research please.
TerryW : I am sorry
carofer : mg .. is it nitric or nictic?
liebermn : ONe of the new initiative is to look for small molecules to treat KD. (I'm going to type this in pieces.)
mgshidler : nitric oxide
poohsdaddy : That sounds like a good idea.
TRAILBLAZER : "Dr. Lieberman, why is it that if our testosterone level is below normal can we not take testosterone to build us back up too have more energy?"
liebermn : "[i]Our strategy is activate the cell's own protein quality control pathways. The idea is to rid cells of the toxic, mutant AR by promoting itss degradation."
Bruce : And how will you accomplish that ... in theory?
mgshidler : i know testoterone is the enemy but what about hgh?
liebermn : "So, trailblazer, testosterone is harmful to KD patients because when it interacts with the mutant AR protein it causes it to become toxic. And this toxicity far outweighs the helpful effects of testosterone on muscle."
Rick UK. : "I have just started taking a drug called AMANTADINE, it's supposed to help with fatigue, has anyone else heard or tried it?"
Bruce : "No, not me Rick"
poohsdaddy : Not sure about all the termonology--still learning about diagnosis and KD
Darwyn : not me rick
TRAILBLAZER : I would love to have some type of drug to allow me to have more energy - I'm sleeping 18 hours a day
liebermn : "So, to find small molecules, we've screened a large set of compounds - a so-called library of 50,000 small molecules -- for compounds that activate a protein called hsp70. "
Rick UK. : "It's given to people with Parkinson's, but apparently, it gives more energy!"
KellyC. : nope never heard of it myself
MikeG : "TJ, you need some of my special blend of coffee... :)"
liebermn : "Hsp70 is a colecular chaperone: a protein that helps other protein behave themselves (just like parental chaperones at a middle school dance) by making sure they fold properly. If hsp70 comes in contact with a misfolded protein, it sends it for degradation."
poohsdaddy : "My neurologist had me try Provigel, but insurasnce did not cover."
Bruce : "Okay, Andy, I am lost on the folded and misfolded part. "
Rick UK. : "I have just started taking it, but it takes a while to take effect. I will keep you all updated."
liebermn : "Sure, sorry. The KD mutation causes the androgen receptor protein to adopt an abnormal shape, something we call misfolding. It's probably similar to the abnormal shape that misfolded proteins take on in other neurodegenerative diseases like Alzheimer and Parkinson."
mgshidler : when liebermn said folded and unfolded did he refer to the mutated antigen receptor
poohsdaddy : "We tried Ritalin for a while, but got very Jittery. The switched to Zolpidem to help sleep at night."
carofer : why not just inject hsp70? Can this be done in mice?
Bruce : "So, Andy, you are attempting to isolate and destroy the bad stuff and leave the good stuff alone?"
liebermn : "Since the KD mutation causes the AR protein to have this abnormal shape, we've been screening for compounds that that activate hsp70 and promote AR degradation. So far, we'"
liebermn : oops. Sorry about that.
liebermn : "So far, we have some good leads that work in a yeast models, and we're now test them in our cell culture system. Our hope is to eventually try them in mice."
Bruce : Are you working with any other labs on this?
liebermn : That's right. This strategy should really help your cells get rid of the bad proteins.
liebermn : "Yes, we're working with another group here at Michigan. Our collaborator is Jason Gestwicki, a chemical biologist."
liebermn : We're also continuing to work with the group at MSU to look at the effects of the mutant AR on muscle.
carofer : It sounds like this might be an application for the use of microarrays. Have you looked at these for assisting in the research?
poohsdaddy : The fact that you are doing researcch is encouraging!
liebermn : "One of the things we learning by studying our mice is that muscle disease comes on early - in fact, before we can detect disease in spinal cord. So we recently send some muscle to our collaborators for microarry study to look at gene expression changes."
carofer : What kills the neurons? Is it testosterone gone toxic?
liebermn : "We're excited about our findings in muscle because it opens up a new potential therapeutic target and lets us think about the disease process a bit differently. So, as Barry Bonds can tell you, the AR protein is made in muscle. And we're now thinking of motor neurons and skeletal muscle as a functional pair, with each supporting the normal function of the other. And we think that disease in either one will likely affect the other."
mgshidler : what about human growth hormone?
poohsdaddy : Thanks to all for getting up early on a Saturday to share information. It helps to know that I'm not alone.
Ron : Yes! He was going to e-mail you.
Bruce : "Can you explain that a little more Andy ... let's us think abour the dease process a bit differently"""""
liebermn : "The mutant AR protein causes the disease. However, in the absence of testosterone, the protein isn't very toxic. We know this because women with the mutation don't get the disease, and female mice with the mutation don't get disease. However, if we give female mice testosterone, they get sick. Something happens to the receptor in the presence of testosterone that makes it toxic."
poohsdaddy : "Do we all get to see everyone's comments, or some limitation?"
carofer : Great concise explanation.
Bruce : Everyone's except for private messages sent to another.
MikeG : "Andy, I once participated in the protein folding study at Stanford ( would it help you research if we were to join that program? If not, what can we do to help you?"
liebermn : "Bruce, one idea that were testing is that disease arising in muscle might affect motor neuron function or survival. So, we know that motor neuron innervation of muscle is important for optimal function of skeletal muscle, and we also know that muscle sends supportive signals to motor neurons. It's our idea that this communication is disrupted in KD and that this contributes to disease."
liebermn : "Mike, I'm not familiar with the study at Stanford. "
Bruce : "Thanks, is this some of the research that was explained in Atlanta ... from the Michigan State attendee?"
liebermn : "Yes. So we're now following up on that study by trying to make a new mouse model of KD. Our goal is to make a mouse that specifically makes that mutant AR protein either in muscle or motor neurons, and use them to determine the extent to which each cell type contributes to disease."
poohsdaddy : Are you aware of other research or treatment?
Bruce : "Over the last couple of years, several carriers have mentioned having many symptoms (less severe and later onset). Has there been any study on women carriers?"
liebermn : "Well, that's one of the really great things about the KDA meeting. In addition to meeting all of which (which is truely the highlight) we get together with other researchers and share our ideas and progress."
MikeG : they decided to distribute computing to everyone who had an Internet connection - the appication on the user's CPU became the new IDLE loop... it causes your computer to do all the protein folding calculations remotely and send the results to Stanford's server. That way they can do more work than any humongous computer could.
mgshidler : this mutation is at the bulbar nerve in the spinal cord right
liebermn : "So, bulbar refers to the nerves that control swallowing muscles. The mutation, in the androgen receptor gene, is in the DNA of all cell types. For reasons we don't completely understand, the motor neurons in that control bulbar and limb muscles are particularly affected in KD. "
liebermn : "And I'm not aware of clinical studies reporting detailed analysis of female carriers recently. In our mouse model, we see relative few affects in females."
mgshidler : why are my calfs wasting more so than other mucles
UTE : So the bulbar may accounts maybe for our dry drowning/esphogil spasms?
Bruce : "Andy, you mentioned that muscle disease (damage) started much earlier then it shows up in the spinal column (I think I have that right). How early are we talking? "
liebermn : "I don't think we have a great explanation for why calves are affected early. In fact, KD often is described as initially affecting proximal muscles more than distal, but this is a generalization and disease progression clearly varies."
poohsdaddy : Two of my cousins also have KD. Our mothers were sisters. The eldest cousin died at 69 a couple years ago.
liebermn : "The bulbar symptoms include swallowing problems, yes."
carofer : back to the prior question of stem cells -- do they show promise?
mgshidler : are there any clues hiding in the progression vareables
liebermn : "Bruce, the muscle symptoms in our mice are seen at 10 - 12 weeks, which are sexually mature adult males, but the spinal cord disease isn't detected until about 2 years."
poohsdaddy : What does this mean to KD patients?
liebermn : "Yeah, I think there are probably important clues yet to be uncovered about why some people progress at different rates than others. One factor we know about is the length of the CAG repeat. Longer CAG repeats in the AR gene tend to cause earlier onset. However, there are probably other factors that also affect onset and progression, and we don't yet have a good handle on these. Studies of large groups of Huntington disease patients have uncovered the fact that there are probably genetic factors influencing progression or age of onset, but these are currently undefined."
mgshidler : any link between repeats and severity of wasting
liebermn : "Poohsdaddy, our analysis of the mice we made suggested to us that disease processes arising in muscle might contribute to the overall pathogenesis. And this suggests that muscle might be a target for therapy."
liebermn : Longer CAG repeats tend to cause earlier onset and more severe disease.
mgshidler : i have 52 repeats is that a medium
CT_Jameson : I also have 52
KellyC. : Lieberman?... is it common for Idental Twins to have kd.... is that common among KD'ers.. have u heard of this before?
liebermn : "So the range for KD patients is from about 40 to high 60s. So, yes, you're 52 repeats falls in the middle."
poohsdaddy : "Thanks, I continue Physical Therapy as often as possible to stay active. "
Bruce : Let me try again. Your labs focus is on the muscles (what is causing the misfolded proteins) and attempting to find a cleaning agent for those misfolded proteins. Is that too simplified?
liebermn : "No, I haven't heard of identical twins with KD before, so I don't think it's especially common. Are your symptoms similar in onset and severity to your siblings?"
Alexandre : I am not Idental twin and my twin brother doesn't have KD
KellyC. : well i have a Idental twin brother he has kd to were both about the same with spasms weakness bulbar etc... etc...
Bruce : "KellyC, do you two get together to compare notes?"
liebermn : "Bruce, that's right. We aren't looking exclusively at disease in muscle because we also believe that motor neuron expression of the AR contributes to the disease. Currently were working to sort out the extent to which these two cell types play a role in disease."
carofer : DNA mutations survive only if there is some advantage to them -- is there some advantage to having CAG repeats?
mgshidler : ct- does this mean we have the same progression rate since we tested at 52? i am doing fairly well with my mobility at 43 yrs of age. my main problem is with stairs. do you have the same problem? my first symptoms were notice at early 20's
KellyC. : My twin and i are about the same progression.... We hhave alot of eye problems as well spasms behing the eyebal etc
KellyC. : Poor vision
KellyC. : Yes we do bruce
mgshidler : what about lifestyle diet and big a role does this play in kd progression?
liebermn : Twin studies have been very powerful for geneticists to define the fact that there are modifiers -- either in the environment or other genes -- that influence disease onset and progression in other polyglutamine disorders.
Bruce : "Kelly, that is interesting about the spasms in the eyes. I had those for years and they finally went away. It is a very weird sensation when it happens."
KellyC. : Yes VERY.... Sometimes my eyes are so sore i cant drive my truck
liebermn : "Carofer, I don't know of a selective advantage for the long CAG repeat in the AR. But, I also don't think there's a selective pressure against in for female carriers, and therefore it persists."
Bruce : "When I explained them to my optimologist, I called them little explosions in the eye. I couldn't figure out a better way."
murf : KellyC. do you use eye drops?
KellyC. : Yes all kinds of them from the speacialist eye doc
KellyC. : He seems to think it maybe k related??????
KellyC. : I DUNNO?
murf : I'm starting to have eye problems too. Since my lasick surgery
murf : I think we all sleep with our eyes open so dry eye is an issue
KellyC. : I assume the eye muscles waste as well causing eye problems over time? i could be wrong i dont know
CT_Jameson : "mgshidler: I am 35. I noticed symptoms in late 20's. However, my mobility has decreased significantly in last 3 years. I noticed almost no problems 3-4 years ago. Now I tire quickly. Stairs are difficult."
Bruce : "Andy, as the disease progresses, I have noticed a substantial decline in the number of spasms. Is this because there are less muscles to effect?"
poohsdaddy : A female cousin's sons were diagnosed with
liebermn : I haven't heard about eye symptoms previously. It will be interesting to ask other neurologists about who see lots of KD patinets.
Bruce : "Thanks, I'll ask Dr. Fischbeck about it also."
KellyC. : yes it would be liebermn ty
poohsdaddy : "als ,but are going to be tested for KD soon"
murf : Angela is now doing an eye test when she asks you to close your eyes. she is looking for one (my right) to open
mgshidler : "i excercise 3 to 5 days a week, light weights and stationary bike. afterwards i take hot baths and it helps alot with muscle pain and tremors. it will also help me to sleep"
liebermn : "Yes, Bruce, that may be right, but it's hard to know for sure. It could be progressive muscle or nerve loss."
Bruce : I call it a negative blessing.
liebermn : "Any other questions before I go. (And Bruce, I like that egative blessing"")."""
CT_Jameson : "Dr. Lieberman... Since testosterone is the enemy that allows the mutant AR to damage the cells, is there anything we can do to lessen our testosterone levels (other than become a eunuch)."
Bruce : "MG, I exercise every day (alternating the types of exercise)."
Bruce : "Thanks, Andy for joining us today. It has been very helpful. We appreciate your time."
Ron : Well men. I must go for now. Stay healthy till next we chat.
Bruce : Thanks also to the entire research team at Michigan.
mgshidler : what about diet and nutrition. thanks andy
liebermn : "Well, the NIH is in the midst of a clinical trial to test a drug used for prostate disease that won't cause complete chemical castration, but might help prevent KD. This is an important study that many of you are participating in."
liebermn : Thanks to all of you. It
KellyC. : Well thank you very much for coming into the chat! Dr-Liebermn.... got to go everyone untill next time...... stay active!
UTE : "Yes, tks Andy, from a fellow Michigander (born in Ann Arbor) "
CT_Jameson : ty!
liebermn : It's really a wonderful opportunity to chat with you. I hope to see some of you at the next KDA meeting.
carofer : "thanks for the good info and update, andy"
Bruce : Thanks everyone for joining us today. Thanks again Andy.
poohsdaddy : "Yes, Thanks for sharing to all, need to pick up on a long distance call or just call them back later."
liebermn : You're welcome. Have a great weekend everyone. I'm off to watch my son play soccer! Bye.
Bruce : "Dart, did your system finally stabilize?"
Bruce : Tell him good luck at the game.