Kennedy's Disease Association

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Kennedy's Disease Chat Transcript  12-05-2009

Topic:  Heather Montie - Research Update

Host: Murray Williams




Bruce: Morning Murray and Heather
murf: morning
Bruce: Oops. No Heather yet
murf: Heather loged in last night
murf: morning God
Bruce: Murray, we are getting the snow you guys had yesterday.
God3n1maloney: hello
murf: u can have it . LOL
murf: Morning Heathger
murf: Heather
Bruce: It is beautiful. We live on a ridge in the forest and everything is covered with white.
Bruce: Morning Heather
HMontie: Bruce Morning All!
Bruce: How is your dad?
HMontie: He is hanging in there. But we wish he was doing a bit better than he mom is taking amazing care of him!
HMontie: thanks for asking:)
Bruce: Good to hear. Caregivers are wonderful!
God3n1maloney: My name is Jami. My husband Greg was diagnosed with Kennedy's a year ago.
HMontie: Yes...thank your wives everyday:)
HMontie: Hi Jami
Paulette24: Hi Heather Dad and I are here waiting
Bruce: Welcome Jani, thanks for joining us today.
murf: Hi Jami
God3n1maloney: Hi all
HMontie: Hi mom and dad...glad to see you on:) I'm proud of your computer skills
murf: U are more than welcome to call us anytime to answer questions
Bruce: I saw that Grand Rapids had some snow. How far are you from there?
Bruce: My email was addressed to Paulette
HMontie: Bruce, I was in Grand Rapids for undergrad. I am in Philly now...and it is rainy and chilly. We don't get anywhere near the amount of snow as GR.
God3n1maloney: I am in Midland, about two hours northeast
HMontie: Oh sorry Bruce:)
Bruce: No problem. Do you know a Doug Chung? He is a professor at Grand Rapids?
HMontie: Jami you are near my parents then. They are in downriver (Lincoln Park)
HMontie: No, I went to Aquinas...where does he teach?
God3n1maloney: Is that near Detroit?
murf: I'm in my green chair lol
Bruce: I think it is Great Valley State University or something like that
HMontie: God3n1maloney is 15 miles south of downtown Detroit Jami
murf: yuck
murf: any crime?
HMontie: murf Murray it is not so bad, we are a bit more suburbia
murf: Houston you can't be that close
murf: I'm 18 miles out and it's starting to rise here
HMontie: murf That sounds similar to where my parents are...the crime is leaking in. Are you getting snow down in Houston?
Bruce: Morning Billeric
murf: We got about 1 in last night
murf: first snow I;ve seen in 13 years
HMontie: murf Wow, I murf can't beleive that!
God3n1maloney: You have more than Midland MI
billeric: Good morningf guys.
murf: I still have some in the flowers
murf: Morning
Bruce: I am in Georgia and we got about 1½ inches this morning. It is beautiful.
God3n1maloney: So do I
Bruce: Morning Gary
murf: It followed the jet stream yesterday
murf: Hey Gary
God3n1maloney: It will come back up here where it belongs. It always does
murf: ok we post so ......
Bruce: And you can keep it
gary_kc: Good morning. This is Gary joining from KC. It is 22 degrees this morning. It is the coldest day. :-(
murf: Heather Monte received her BA in biology from Aquinas College (2000), Ph.D. in Physiology from Wayne State University (2005) and is now a postdoc in Dr. Diane Merry’s lab where she studies SBMA. Heather became interested in researching SBMA due to her personal experience with the disease (her father, two uncles and a cousin have SBMA). She has recently published a portion of her postdoctoral project that has defined the role of the nucleus in SBMA. Heather Monte received her BA in biology from Aquinas College (2000), Ph.D. in Physiology from Wayne State University (2005) and is now a postdoc in Dr. Diane Merry’s lab where she studies SBMA. Heather became interested in researching SBMA due to her personal experience with the disease (her father, two uncles and a cousin have SBMA). She has recently published a portion of her postdoctoral project that has defined the role of the nucleus in SBMA.
gary_kc: Hi murf!
Bruce: I was born and raised in Minnesota. I think the snow is great, but the cold is too tough on me these days.
gary_kc: Hi Bruce!
HMontie: Jami, where does your husband for neuro clinic? My dad's neurologist in at Henry Ford in downtown Detroit and he is amazing. If you ever would like to meet with him please let me know and I can give you contact info.
murf: Her research now focuses on nuclear AR events that may be involved in pathogenesis, with the goal of determining additional therapeutic targets. She received a KDA grant to study how an AR modification called acetylation impacts disease. The preliminary results she has generated with this grant has allowed her to apply for another grant from the NIH, which (if funded) will enable her to begin an independent research program in SBMA.
loshimo11: Hello everyone. This is Luis Shimomura joining in from a rather chilly San Francisco.
God3n1maloney: He has been going to U of M in Ann Arbor. That's where he received his diagnosis
Bruce: Morning Luis
HMontie: Moring all you that have just logged on
murf: Heather how is your research going?
Bruce: God3N, who have you been seeing at U of M?
HMontie: It is going great Murray, I am making good progress....a little at a time.
HMontie: U-M is a great hospital..Jami. Glad to hear.
murf: can you give us a breif in English what you do ... lol
Bruce: Welcome dbymay
HMontie: Sure can
God3n1maloney: He has seen Dr Gruis and Orme. He has seen a nurse practioner and a physical therapist
HMontie: So, as you read in my bio I have found that the mutant androgen receptor (with the expanded CAG tract) needs to be in the nucleus with it's ligand (testosterone or DHT) to be toxic
HMontie: I have also found that if we keep it in the cytoplasm it inhibits disease in cells and in mice
murf: oh
HMontie: That is the work I published a few months back. I am also working on another project that the KDA funded
God3n1maloney: He is an iron worker. His legs are the most affected part of his body right now and is having great difficulty. He should be on disablitiy, he has started falling now and then at work, but we don't know how to go about that without losing everything we've worked for.
HMontie: One thing about keeping the AR in the cytoplasm is that it can't do its ""day job""...which we want it to do
Bruce: Heather, is there currently a drug that keeps the AR from entering the nucleus?
murf: maybe thats why Avadart did not work
Bruce: Morning Michael
murf: hey mike
michael17860: Hi All
HMontie: So leuporelin, the drug they used in Japan, which inihibts testosterone formation keeps the AR out of the nucleus.
HMontie: To an extent, Avodart does kind of the same thing, since it inhibits the more potent androgen (DHT) from being made.
Bruce: Oh, that takes us to the chemical ""C"" word that men do not like to use.
murf: can't
HMontie: Yes Bruce you are right, leuoprelin is a chemical form of the ""C"" word
murf: lol
murf: ok dry humor
loshimo11: Wait... Let me cross my legs...
Bruce: Diane Merry also uses the term ""to do its day job"" ... I like that term.
HMontie: The work I have done to keep the AR out of the nucleus is more of a ""proof of principle""...not a direct means to a therapy
HMontie: I learned from the best:)
murf: but still needed
HMontie: Rather, my work gave us clues as to what we need to focus on the direct a therapy towards
HMontie: And that is events that occur within the nuclues when the mutant AR is there...that lead to toxicity
HMontie: so that has lead me to the project the KDA has funded me for over the past year...thanks again!
Bruce: I just believe us farm boys have a problem with the ""C"" word.
murf: if you get NIH funding and your own lab ... will that make 4 specifically working on Kennedy's?
murf: 4 labs
HMontie: I think we call agree that ALL men would havea problem with that word Bruce:)
Bruce: :)
HMontie: Yes Murray, the grant I applied for would allow me to train with Diane for two more years and then start me own lab...and it is ALL SBMA work for now
murf: Woo Hoo
HMontie: Cross your fingers I get it!
murf: we are so lucky to have all the support
HMontie: The project concerns a modification that normally occurs to the AR...called Acetylation
HMontie: Acetylation is the addition of a chemical group to the AR protein, which allows it to do various things withing the nucleus
HMontie: There are a few parts of the AR protein upon which this ""modification"" occurs
HMontie: I have found (with the KDA money) that if you inhibit this modification it inhibits the toxicity of the mutant AR.
HMontie: But, this poses a little bit of an issue, because inhibiting this ""modification"" decreases the AR's ability to do its ""day job""
Bruce: Got it.
murf: that is big bang for your donated dollar
HMontie: So, I have also found, that if you just ""toggle"" down this modification a little bit, it still rescues cells and motor neurons from mutant AR's toxic effects
HMontie: Hi Uncle Gerry!
gmontie1: Hi, its Uncle George
murf: so they regenerate?
Bruce: How does acetylation figure into this process (what is supposed to happen or what doesn't happen)?
murf: the cells I mean
HMontie: Oh>...even better:) !!! So glad to see you on here...saw the G and thought it ws Uncle Gerry...he and Aunt Maria are supposed to be on today too
Paulette24: Hi Gerry and George It's Ed and Paulette
murf: Hey Gerry !!!
HMontie: So Murray, the work I have done are in cultured motor neurons from our mice...and can only show right now that we can stop them from dying
murf: thats important lol
HMontie: Bruce, actetylation allows the AR to normally interact with some protiens and to DNA in the nucleus so it can ""activate"" genes that it normally turns on or off..
billeric: Really important!!!!!!!
HMontie: that is some of its ""day job""
Bruce: Morning Utah
Bruce: Formally Mich
UTE: Morning Allo
HMontie: the studies I have done in the motor nueron culutres need to be repeated, but are promising
HMontie: and those studies, along with some in other cell lines are using a protein that is a hot topic in the field of aging
HMontie: That protein is an enzyme that acts to take off acetyl groups from the AR.
HMontie: It is exciting because it means we can ""tell"" that protein to do ITS job more and make the mutant AR less toxic that way
HMontie: There are drugs that are known (but not ready for humans) and being developed to activate that enzyem
HMontie: So my work is not ready as a means of therapy right now, but is moving in that direction
HMontie: any questions thus far?
Bruce: What is the next step?
HMontie: So i need to further validate this work in my cells and in the motor neurons (which is still part of the KDA grant).
murf: 1000 but go a head lol
michael17860: Any time line when therapy might be ready?
Bruce: Michael, that seems to always be the question we KD'rs ask.
HMontie: The grant I applied for from the NIH would allow me to test it out in the mice; which is an important and crucial next step
Bruce: Morning Dean
michael17860: I know, I cant help it.
Bruce: I don't blame you. The older I get, the more I want to see that treatment.
dean: good morning everyone
murf: the last time I spoken with Kurt & Angela we are at lest 2 yrs away from another clinical trial
HMontie: So it will be a few years (if all goes well), but I can't put a number on it. however, there are some other therapeutic avenues in the pipelines that will come sooner and are also promising
murf: Hey Dean
Bruce: Like what?
michael17860: That good news.
HMontie: and that is right about what Kurt and Angela said.
Bruce: IGF-1 looks promising also.
HMontie: I beleive that there is talk about targeting IGF1 (Maria Pennuto's work) and Diane spoke of some other compounds that modulate the AR in her CHAT
Bruce: Yes
Bruce: But, the end goal is to find something that works while still allowing the day job to be done. Right?
HMontie: Does anyone need a more laymen's explanation about anything I have already spoken of, or just in general?
murf: beaner?
murf: lol
murf: I love u
Bruce: Yes ... THat always helps.
HMontie: Yes that is right Bruce...the AR does ALOT of normal ""good"" things in the cell (motor neurons and muscle) that we want it to continue to do....while we also INHIBIT te ""bad"" things the mutant AR does
HMontie: Beaner?
murf: beanergirl just loged in
Bruce: This defect (mutation) does not allow the AR to process DHT correctly ... is that correct?
HMontie: oh..sorry, thought you were asking me something
Bruce: Morning Jeffrey
HMontie: Bruce, no quite Bruce. The mutant AR can still ""bind"" DHT...
Bruce: But, ?
Bruce: Morning Ed
HMontie: Bruce, are you getting at the ""loss of function"" of the AR that seems evidents in patients?
Ed M: Hello all
Bruce: Yes
HMontie: About time ED! :)
Jeffrey S. Pauly: Good Morrning.... I tried signing in as poohsdaddy, but it wouldn't accept me for some reason.
MikeG: :)
Ed M: I am having computer problems
MikeG: MS OS?
Bruce: Jeffrey, contact Terry Waite afterwards by email and explain your problem. He might be able to help.
Ed M: hard drive problems
HMontie: So, we (and you guys know) that your AR doesn't work up to par. Studies have shown that that lack of work contributes to disease, but I beleive (and think alot of us do) that that ""loss of function"" is NOT the PRIMARY cause of SBMA....just adds to it
MikeG: :(
Ed M: am trying to recover data and files from a drive that says there is nothing there
Paulette24: Hi Ed M This is Ed and Paulette, Heather Parents
HMontie: MikeG is that a confused or sad face? please expand
Ed M: How are y'all doing?
MikeG: just referring to Ed's problem...
Ed M: We had a touch of Michigan weather yesterday - I saw 5 snowflakes
HMontie: Ed M Doing good Ed, do you have snow down there too? None here in Philly...oh don't you miss it?! :)
Paulette24: OK
Bruce: Ed, is our resident ""explainer"". When we get stuck and do not understand something in the research area, he has a way of explaining it that even I can understand ... usually anyway.
Ed M: HMontie - so have you been able to keep up with all the questions?
HMontie: Yes...Ed does a good job at that. And yes I am doing pretty good I think Ed:) I hope!
Jeffrey S. Pauly: Our son and daughter-in-law live in Central Philly; and we've ben there a few times.
Bruce: I am always impressed with our researchers, because they have dozens of questions thrown at them and they do a good job of trying to explain things so we laymen can understand.
HMontie: Jeffrey S. Pauly, I work at Thomas Jefferson Univeristy right in center city. How do they like Philly?
murf: Heather u r doing Great!
Ed M: Bruce I am impressed on how they can type so fast to keep up
HMontie: Bruce murf ..thanks! And we are always glad to do it.
Paulette24: Heather ditto
HMontie: Ed M It's from all the grant writing we have to do with deadlines:)
Bruce: So, Heather, is your focus more on finding something that will allow the day job to be done, but counteract what the mutation prohibits the AR from processing correctly?
HMontie: Now what is better than having your Mom's approval? :)
Bruce: Moms are great
murf: my typing is getting worse ... keep hitting wrong keys
Jeffrey S. Pauly: Missed out on chats since October 5th.... Broke my leg and spent that time in the hospital and Nursing Home trying to learn to walk all over again. They love being in Philly; and we enjoy our visits too!!!
beanergirl: heather did u see the dvd i sent u ?
HMontie: Bruce correct Bruce, but even more importatly we need (want) to inhibit what the AR does wrong to cause cell death
murf: Jeffrey S. Pauly u ok now?
HMontie: Uncle Gerry beanergirl is you? :) I watched some of it this morning but didn't get to finish. But I get the general idea. Do you have a specific question about it? (Epigenetics)
beanergirl: yeah, maria's logg in
Bruce: Heather, you have quite the family audience today. That is great! Your family has reason to be proud.
Jeffrey S. Pauly: Murf, better, but still need severay weeks of PT,
beanergirl: is anyone exploring this tract? /why not?
HMontie: Jeffrey S. Pauly sorry to here:( Glad you are back now tho! Stay tough. My dad used to fall and break his legs all the time too. Be careful!
murf: I'm going to be in trouble if I break another bone
HMontie: beanergirl Do you mean as far as effects on the AR gene or others?
beanergirl: yeah
Jeffrey S. Pauly: Thanks for the good advice ... It's not the fall that hurts; It's the sudden ""
Bruce: Several of us have several broken bones that show our walking capabilities (or falling capabilities).
beanergirl: ar
Jeffrey S. Pauly: stop
Bruce: :}
Jeffrey S. Pauly: I'll need to reas up on chats that I've missed to catch up on things.
murf: I don't walk anymore so I should b ok
Bruce: Heather, who else are you working with on your current projects?
Jeffrey S. Pauly: read
MikeG: took me 12 weeks to recover from 3 broken metatarsals in my left foot!!!
HMontie: No, beanergirl, for the most part the AR is expressed in a similar fashion among men, but methylation status may alter the amount that is expressed and this may contribute to various levels of severity among individuals
MikeG: good thing about being in the chair is I didn't have any back pain for 12 weeks! lol
HMontie: But, a ton of other genes may also be contributing to variaiton in disease among men, that is really too cumbersome to explore at this point in time
Bruce: Heather, can you amplify on what you just mentioned about ""severity"".
michael17860: Heather this might sound like a dumb question but, Is there a chemical change when a man gets his tubes cut to stop sperm production??????
HMontie: Bruce, I mean that there seems to be some variation in the onset and speed of progression of SBMA among patiens.
HMontie: patients
UTE: I've broken the metatarsals in both feet but not at the same time...amazing how they heal eventually
murf: one of the foot bones I broke a few yrs ago did not heal proporly and is giving problems
Jeffrey S. Pauly: Does that make a difference to guys with KD?
HMontie: There are and could be MANY factors that contribute to this both genetically and enviornmentally that we don't fully understand. But we do know that the greater the CAG tract, disease usually begins earlier and is a bit more severe
Bruce: There seems to still be some questions as to why some men have onset at 20 or 30 and others at 60+. That still needs to be explained.
murf: swhould we encourage deposits in the sperm bank for younger members?
dbymay: Please explain CAG tract, thanks
HMontie: michael17860 I do not beleive that inhibiting sperm formation has any affect on testosterone levels and thus any changes that would alter SBMA.
murf: k
michael17860: O K Thank You.
Jeffrey S. Pauly: HMontie, each patient has similar symptoms, but the onset and progression seem different. Is there any predictability? based on your research?
HMontie: murf I do not feel that I can make any suggestions such as that. Storing sperm is a personal choice and the idea of it should be consulted with a physician. We know that SBMA patients have reduced fertility, but are still capable of producing offspring...look at me:)
MikeG: I need to go - great chat Heather, thanks a million and keep up the fantastic research!!!
murf: thank God for u!!
HMontie: dbymay CAG are three parts that make up DNA and in SBMA there is a tract of CAGCAG that is expanded in the AR gene. CAG in DNA codes for a protein called glutamine, which is why SBMA is referred to as a poly-glutamine expansion disease. Is that sufficient?
Bruce: Heather, has it been proven that the higher the CAG, the earlier the onset and severity of the disease? I always thought that, but I believe I read somewhere recently that it might not be the case.
dbymay: Yes thank you
murf: Look at TJ and me
HMontie: Jeffrey S. Pauly, well not base on my research, but research in the field makes the case that a higher CAG number coorelates with an earlier age of onset, but cannot predict a specific age with a specifice CAG number. There are other variables at play as well that we don't understand
murf: TJ is 102 CAG
murf: I'm 48 CAG
HMontie: MikeG by Mike! Thanks!
murf: he is better than me
billeric: Mine is 48 also.
michael17860: Heather does the CAG stay the same, or does it change with time and severity?
murf: we r one month out in age
Bruce: Murf, I thought the highest CAG count so far (recorded) was 57. I could be wrong, but I think Kurt said that.
murf: oo[ps
murf: sorry
murf: fingers
murf: TJ is over 100
Bruce: There are still so many unknowns with KD. That is the frustrating part.
Jeffrey S. Pauly: Thanks! There are things that don't understand, but I'm always willing to learn more about KD.
murf: and still walking
HMontie: murf Wow. Is TJ your brother Murray? Or friend? THere is some work the the Huntington's Disease field that shows (in mice) that a VERY high number of CAG's in the huntingtin genes causes less disease compared to a moderate expansion. This may be in part because that HUGE expansion might decrease the expression of the gene or may decrease the protein's ability to get in the nucleus. But it is not completely clear yet.
murf: no friend .... Noack u met him in Vegas
HMontie: Can you please suggest that he speak with Kurt about getting his CAG recorded? It would be VERY useful!
murf: sister Lousie (Weaser)
Bruce: Heather, if we have a conference this coming year in San Diego, do you believe you will be able to come?
murf: He has been to NIH with Kurt
murf: I don't knoe why we don't have it
billeric: Me neither
HMontie: michael17860, in dividing cells is known that the CAG tract can expand (and to a lesser degree contract)....and we know that motorn neurons do NOT divide. You keep the same ones you were born with. But, there is also some data that there can also be changes in the number of CAGs in non-dividing cells, but I beleive that the rate of that change is less than in dividing.
Jeffrey S. Pauly: What happened to the idea of a conference in Chicago?? Why San Diego?
HMontie: Bruce, is that where SFN is next year (sorry I have not looked into where it is next fall).
michael17860: Thank You again Heather.
murf: yesw
beanergirl: it always follows a
murf: west coast SD
murf: Nov mid month
Bruce: Yes, SFN is in San Diego. We are talking about having our conference right before SFN.
Bruce: Nothing confirmed yet, however, just talking.
murf: Chicago was an idea for this yr
michael17860: By all, Got to go, Thank You Heather for a Great Job....God Bless
Bruce: We had a poor response this last year about a conference in Chicago. Economy? So, we had to cancel plans.
murf: last month
Bruce: Well, I have to take my dog for a walk. He is chomping at the bit. Heather, thank you thank you thank you ... We appreciate all that you do.
murf: yes we do
Jeffrey S. Pauly: Thanks to all for being here today.. Bye till next time.
HMontie: Jeffrey S. Pauly, SFN was in Chicago this year and that is why there was that talk. But, as others said the KDA has had conferences right after or before SFN so that researchers can easily attend. SFN is the society for neuroscience conference that we go to to present our reserach and learn from others.
murf: like we can't express how much
HMontie: michael17860 by! Great talking to you too!
gary_kc: Heather, thank you very much for joining us this morning. It was a great chat.
HMontie: Bruce , bye! Glad to talk to you. Take care.
HMontie: I can stay on a bit if anyone else wants to chat more.
gary_kc: I got go. Stay warm all. Bye.
murf: Heather , thanks for taking the time. we always love talking to u
dbymay: Heather, thank you for taking the time to help us better understand KD and what is being done to help us all.
Paulette24: Heather, great job as aways How is Grandma and Grandpa's Lexie.
beanergirl: Your uncle thanks you Bye
HMontie: And I love talking to you all and hope I get to see you next fall. If you have a conference I am there come wind, rain or storm:)
HMontie: Bye Uncle Gerry and Aunt Maria.
gmontie1: Thanks Heather. I have some catching up to do. You've helped.
murf: we will becuse of the friday meeting y'all have at our conference
gmontie1: Lexie is great as always, Paulette.
HMontie: Glad to hear Uncle George. How are you and everyone? I will be in town for the Montie Holiday party...I hope to see you all there....please encourage your brood to attend:)
murf: we'll be in San Diego
billeric: By guys. Stay upright.
gmontie1: We'll be well representd. I""ll be talking to you then. Bye.
HMontie: Uncle George I think she is talking about my dog Lexie:) But glad to hear Donnie's daughter is great:) And the rest of your grandkids?
murf: I'll stay seated lol
murf: bye now
HMontie: Mom, Lex is good. John brought her to dog park this morning and trying to get her to groomer today cuz her skin is dry. he is a good doggie daddy:)
gmontie1: Oops.
UTE: Sorry to show up late...tis the season..thanks for all the info Heather..yall have a great week
HMontie: :) You all better stay up right and do whatever you need to to not fall and break anything...especially if there is already snow in Texas!
HMontie: Thanks for having me guys! It was a great way to start the day!
HMontie: Anyone else with any burning questions?
Paulette24: By everyone a great chat day
HMontie: Bye mom...thanks for joining:)
Paulette24: Heather, Dad says great job on all you do. I think he enjoyed the chat.
HMontie: Good:)
HMontie: Ok, I think I'm gonna head out...I have to get some errands done then go into the lab:)