Kennedy's Disease Association

A Public Benefit, Non-Profit Organization

"I am very glad to see that you have added the personal stories, they are a great help. They give an outlook on what to expect with such a disease. It makes me proud to see people who are willing to express and share their stories with the world, keep up the good work!"

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The KDA's mission is to inform, support, educate, fund research, and find a cure for Kennedy's Disease 

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Kennedy’s Disease (spinal and bulbar muscular atrophy) is an adult-onset “X” linked inherited disease with symptoms usually beginning to appear between the ages of 30 and 50.

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The Kennedy’s Disease Association has worked to educate others about this lesser-known disease and to support clinical research efforts.

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It takes an enormous amount of money to fund research…more than any of us can afford alone, but together, we are capable of great accomplishments.

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It is passed on from generation to generation in families worldwide. Males generally inherit the disease symptoms and females are the carriers.

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The KDA Archives

In this section you will find older articles of chat room transcripts, research updates, News, Conferences, etc.

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Topic:  Research Update

Guest:  Christopher Grunseich, MD

Host:  Mike Goynes

 

MikeG   Good morning everyone - I see we have some earlybirds today...  :)
Alexandre   Kennedy's Disease Chat
MikeG   How are things down South today, Alexandre?
Alexandre   Good Morning Mike, here is Alexandre from Brazil!!
MikeG   Someday, God willing, I'd like to come visit you.  It really looks beautiful down where you are!
Alexandre   We have a nice sunny day here, what about there?
Alexandre   Have you seen the pictures about my place?
Alexandre   I would be very happy receiving some folks from KDA here at Estância "Kanaan"!!
MikeG   We have some clouds but it is already 81 here.  Yes, I've seen some pictures of your area... I don't remember how I got them though.
MikeG   Are you going to try to make it to the KDA conference in San Diego in November?
Alexandre   I have one site www.estanciakanaan.com.br, but the moment we are remaking it!!
MikeG   Morning Gopher
MikeG   that may be where I saw some photos
Alexandre   I don't go to San Diego, but perhaps the next year in the east coast!!
Gopher   Good morning everyone from MN. Been so long forgot how.
Alexandre   Perhaps you can realize a conference here in Brazil some time...
MikeG   :) - glad to see you're back!
MikeG   that would be great!!!
MikeG   For those who missed seeing this intro for Dr Chris in the message earlier this week:  Christopher Grunseich, MD is a clinical research fellow who is working in the Fischbeck lab at the NIH (NINDS) on basic science and clinical studies in SBMA. Chris completed his medical school training at SUNY Stony Brook and neurology residency at Georgetown University. He and Angela Kokkinis are completing an exercise study in SBMA and anticipate starting other clinical studies soon.
Alexandre   You organize the conference and I'll can organize the place and accomodation to do it!!
Alexandre   Thanks for the information about Dr. Christopher...
MikeG   Anyone who has been to the NIH for the exercise trial has met Dr Chris and knows how thorough he is with examining and recording.
david   Good Morning All
MikeG   We are all eager to hear how the trial is going and what's next as far as clinical trials go.
MikeG   hi David
MikeG   hi Tom & Bruce
Alexandre   Good Morning David
Bruce   Morning
Alexandre   Good Morning Bruce
MikeG   We're honored to have Christopher Grunseich, MD [NINDS] as our special guest today.  He should be signing in any minute now.  When he does, lets give him our attention and cut the small talk.  What he has to offer is very important to us all.
soapman1   Good morning from NC. Very interested in updates on current study .Thanks Dr Chris for your research.
Stewart   Hi Good morning from SoCal
MikeG   hi Stewart
UTE   Kennedy's Disease Chat
MikeG   hi UTE
MikeG   Good morning Dr Chris!
chrisgrun   good morning everyone
MikeG   Welcome!
chrisgrun   just chris is fine. great to be here.
Bruce   Morning Chris, thanks for joining us today.
chrisgrun   I could start to discuss the exercise study first if that is OK.
Alexandre   Good Morning from Brazil Dr. Chris!!
chrisgrun   Wow, from Brazil. that is terrific!
MikeG   Great'
chrisgrun   The exercise study has been going well. we need a few more participants to finish the study.
Alexandre   thanks!
chrisgrun   so far the exercises have been tolerated well by all of the participants. we are looking at two different types of exercises.
chrisgrun   both types so far appear to cause no significant harm, and we have not had to stop the study for any participants because they became too weak.
Gopher   [u]I would be willing to particpate, if you need more people
mattsenac   I am also willing to participate Chris
chrisgrun   Yes, it would be great to have potential participants contact us. e-mailing Angela Kokkinis would be the best way
chrisgrun   We have been collecting a significant amount of data that has helped us learn more about the disease and plan for future clinical studies in KD.
chrisgrun   Angela and Alice are also collecting information on qualitative data. to see if we can identify new measures to keep track of during our studies.
mattsenac   Where are your studies being done?
Bruce   Abgela's email address is:  This email address is being protected from spambots. You need JavaScript enabled to view it.
BobK   morning folks from Toronto
chrisgrun   the studies are done at the NIH in Bethesda, MD.. thanks for sending the e-mail address Bruce.
chrisgrun   Hi BobK.
BobK   Hey Dr. G, Hope things are well
chrisgrun   We have also been doing work on liver metabolism in KD. and we will be having more patients come back in to analyze liver function in the future.
Bruce   Chris, could you take a moment and discuss why you are working on the liver function?
chrisgrun   Angela has been great to work with during this study, and the participants have been very cooperative.
chrisgrun   Sure, the liver function is something we are exploring since patients have reported to have elevated liver function tests, and this is thought to come mostly from muscle. however, some patients have had liver ultrasounds which show liver fat.
Bruce   Connection reset by peer
chrisgrun   we are in the process of collecting this information systematically. and doing MRI measurements to quantify the liver fat.
chrisgrun   we do not yet know whether or not the liver changes are harmful or if they are benign.
chrisgrun   we will need to do liver biopsies eventually to evaluate for liver damage or scarring.
Alexandre   I've done a check up recently and the only probelm I had was live fat!!
mattsenac   I have been told I have a fatty liver but the Dr's dont seem to think much of it
chrisgrun   it is interesting to us that there may be liver involvement, since the androgen receptor is expressed in the liver and IGF-1 is synthesized in the liver.
chrisgrun   We are also doing work with the SBMA mice to determine whether or not they have changes in their liver tissue.
Bruce   Elevated CPK is fiarly common  for those of us living with KD.  The liver fat issue I had not heard of.  What might cause that?
chrisgrun   We will have MRI information on approximately 20 patients within a few months.
chrisgrun   Many processes in the liver could potentially cause the liver fat, changes in liver stress, alcohol consumption. or perhaps changes in the way in which proteins are turned over...like autophagy. We do not know the answer yet.
Bruce   Thank you.
soapman1   do we contact Angela for that study as well?
chrisgrun   we do not know why KD patients would have this finding. but it may tell us something about how the mutant androgen receptor is functioning.
chrisgrun   yes, you can contant angela regarding the liver study as well.
chrisgrun   We should have results from the exercise study by the end of the year.
MikeG   Does the study involve biopsy of the liver?
Gary_KC   Good morning. This is Gary Joining in Kansas City.
MikeG   I know John C. had that...
chrisgrun   we are asking all of the participants in the exercise study to maintain a diary. so that they can keep track of their exercising in the future.
chrisgrun   there are no biopsies that we can do now. we are in the process of writing a new clinical protocol that would allow us to do the liver biopsies.
chrisgrun   we would not have to do the biopsy on many patients.. just a few to determine whether or not the change is causing any harm to the liver.
Bruce   Chris, I have been exercising every day for years.  I also keep a daily journal and find it very helpful when looking back upon my experiences.
chrisgrun   yes, it is great that you are keeping a journal. it is good to look back and know whether or not it is helpful or harmful.
chrisgrun   the patients overall appear to feel better after exercising. we are also looking at measurements of depression , mood, and quality of life scales.
dean   What kind of exercising are you doing that is helpful?
Bruce   How many patients are currently participating in the trial?
chrisgrun   there are 45 patients who have been enrolled. and we need another 5 patients to finish the study.
chrisgrun   we have had about 10 subjects screen out because they were too strong.
MikeG   you just found 2 today in the chat... :)
Bruce   Boy would that be nice. :-)
chrisgrun   generally, it you can stand sustained on your heels and toes, then most likely you would be too strong..
chrisgrun   it would be great if you would be interested in participating..
chrisgrun   we are also collecting information on many different blood markers including IGF1
mattsenac   I live in Tampa FL is there a way to participate from here?
chrisgrun   previously we have found from the dutasteride study that subjects had low IGF-1 levels, and that seems to be holding up with this exercise study also.
chrisgrun   Yes, you can participate from Florida. if you contact angela kokkinis (e-mail above in chat) we can arrange for your transport to the NIH.
BobK   The exercise trial good study. Great initiative on part of NIH. My neurologist in Toronto very interested to hear on the outcome
mattsenac   Thank you
chrisgrun   it has been a great experience working with the KD patients. we are excited to start new studies in the future.
MikeG   How are the studies with IGF-1, ASC-J9, and JM17 coming?
chrisgrun   there are a few that look encouraging. and one should start before the end of the year.
chrisgrun   the JM17 study will not be the priority at first. the results from the recent animal study were not as robust as we had hoped they would be.
chrisgrun   there was a recent animal study that was completed by our group. Carlo Rinaldi, a neurologist in our group. The results did show some effect on muscle weight, but there was no significant effect on survival .
chrisgrun   the previous study done in Rochester showed more significant effects.
chrisgrun   overall, we will need more data before deciding to proceed with any human studies of JM17.
chrisgrun   The other drugs/treatments are more encouraging and studies with these drugs will likely start first.
Bruce   The Clenbuterol pre-trial results were interesting, but not encouraging.
chrisgrun   The first drug study will hopefully start before the end of the year, we hope that the NIH will be the site where this first part of the study will occur.
Bruce   Please keep the KDA advised, so we can send out an announcement with registration information.
chrisgrun   yes, this was interesting. a different type of drug than those that were previously tested in KD. the effects could be further investigated, but it will not likely target muscle loss.
BCPaul   depression and fatigue seem to be common, any thoiughts on the use of nootropicfs
BobK   There was mention on NIH site of genetic/ monitoring type study - for women. Did that initiative end up proceeding
chrisgrun   Yes, it is good to get evaluated if you feel as if you may be feeling depression. it is good to get treatment from a psyciatrist if this is the case.
chrisgrun   yes, we are beginning to collect this data on carriers. Alice Schindler is sending out surveys to identify those females who are having symptoms.
BobK   Thanks Dr. G, I'll pass it along.
chrisgrun   if we find those carrier females who are having symptoms we can do further workup to determine if they also have evidence of neuropathy, muscle loss, cramping, liver changes ..
chrisgrun   There have been many carriers who are having symptoms, and it would be good to learn more about this.
Bruce   Several carriers in our registry have commented about symptoms.  Some appearing earlier in life.  I think this will be an important study also.
soapman1   Any particular drugs or vitamins we should avoid?
chrisgrun   Yes, there are different types to avoid. In general it is good to avoid sedatives, because this will contribute to fatigue. it is also good to avoid excessive vitamin B6, as this can cause worsening neuropathy. Anesthetic agents can also cause more muscle weakness depending on the dose that is used. Avoid botox.
MikeG   my mother had severe cramps!
chrisgrun   There have been patients who have had cramping with statin drugs for hyperlipidemia, but this can occur with these drugs, and it is beneficial to have low cholesterol.
mattsenac   Chris can you provide  Alice Schindler e-mail
chrisgrun   cramping appears to be a common finding if carriers are having symptoms.
MikeG   is B-6 the only one to avoid?
mattsenac   Also what about testerone?
chrisgrun   This email address is being protected from spambots. You need JavaScript enabled to view it.
mattsenac   thx
chrisgrun   B6 is a vitamin to avoid because it can cause neuropathy if taken in high doses. It is good to take a multivitamin.
MikeG   I'm taking 5mg of B-6 now...
chrisgrun   I would take a mutlivitamin to get B6, and not take any additional supplementation. It is fine to take additional amounts of B12.
chrisgrun   B12 is helpful for the nervous system.
chrisgrun   Testosterone is something that we do not recommend because of its association with toxicity in the animal model of SBMA
MikeG   good - I'm taking 30mg of B-12
chrisgrun   We know that higher testosterone levels are associated with increased strength in patients, however, we also know that its presence is linked to the disease.
chrisgrun   We do not recommend that KD patients start taking this.
mattsenac   I have a very low level and tried it for a month but it just made me shake more
mattsenac   so I stopped
soapman1   So the 6 mg of b6 in a multi vitamin is ok?
chrisgrun   Yes, the B6 level in a multivitamin is OK, but I would not take any additional amounts.
chrisgrun   We do not yet know how different concentrations of testosterone are interacting with the disease severity.
Bruce   I also take a B suppliment pill along with my multi.  Perhaps I need to rethink this.
MikeG   me2 Bruce!
Gopher   Need to go..will read the end later THX Info helpful!
chrisgrun   Drugs and treatments that are being tested in the future will hopefully preserve some of the beneficial functions of the androgen receptor while stopping the toxic functions.
mattsenac   Thank you Chris I am very happy you joined us this morning and hope to work with you and your associates in the near future
dean   So do not take testosterone.
chrisgrun   In general B vitamins are good, but the B6 specifically can be bad if taken at a high dose. it really depends on which B vitamin it is.
david   I also have a very low level of testosterone normally and have been on a low dose supplement for a few years and it seems to help me.  It is carefully monitor by my endocrinologist
Bruce   In earlier discussions, it appeared that IGF-1 would be beneficial for pre-or early onset and not so favorable for thos of us much older.  Is that still the view?
chrisgrun   Yes, it is good that you are being carefully monitored. this is helpful. Don't take too much so that your levels goes high.
chrisgrun   It is interesting that you mention the age/progression association with IGF-1. The levels normally decline with age. We see that our younger patients are the ones with the lower levels of IGF overall.
david   even with the supplement my tested levels remain below the low end of the "normal" range
soapman1   do all KD patients have neuropathy and does the IGF-1 slow it down.How old is old?
chrisgrun   For studies in the future we will monitor IGF-1 levels
chrisgrun   Not all KD patients have neuropathy. However, in most patients, even if they do not notice sensory changes, they can be found if an EMG or nerve conduction study is done. we do not know whether or not additional IGF-1 will slow down the disease.
BCPaul   are the age related neuopathy symptoms related to CAG repeats <50>?
chrisgrun   There does not appear to be an assocaition that I know of between the CAG size and the type of symptoms. Only the CAG size and the age of onset of the disease.
chrisgrun   We have seen some patients in our clinic who have had the onset of weakness before age 20.
chrisgrun   they had large expansions, over 60.
Bruce   Neuropathy has been a frustration for several yers for me.  It progressively gets worse.
chrisgrun   yes, the neuropathy can be frustrating. There are patients who can experience pain, but this is rare.
Bruce   WOW - over 60 is pretty well unheard of.
chrisgrun   usually the neuropathy is causing more sensory loss and not pain.
soapman1   That's my experience
chrisgrun   We have had one patient recently who responded well after he started taking neurontin for the pain and cramping.
Bruce   Mine is both, but more loss than pain.
chrisgrun   Yes, we were surprised that this patient had over 60.
MikeG   I take neurontin or gabapentin.
MikeG   it will be interesting to see how those patients with CAGs of over 60 progress as they age.  We need another survey...
BobK   Are most instances for onset of symptoms a fair bit later than 20yrs old.
chrisgrun   The neurontin is a good medication, but it is also important not to take too much.
MikeG   I take 300mg twice a day
mattsenac   quinine seems to work great for cramps is that OK in low doses?
chrisgrun   Yes, most patients have the onset of their weakness in the 30's and 40's with some even later than this.
BCPaul   When you speak of sensory loss, does this also extend to nerves like the Vagus nerve and awareness of Gerd , bladder symptoms?
MikeG   seems to help the dry drowning - for me anyway.
chrisgrun   300mg twice a day is fine.  it is very specific to the individual patient.
chrisgrun   yes, quinine is good. it is tough to get in the US.
BCPaul   Has"t Quinine been linked to tinnitus?
chrisgrun   usually the gut and autonomic nervous system are spared in KD. this is fortunate.
mattsenac   yes but it is in tonic water just enough for me
chrisgrun   i am not aware about the assocation with tinnitus, although this may be possible.
chrisgrun   one of the drug studies in the future will likely be multi site. we will hopefully do the first part of the study at the NIH.
chrisgrun   the NIH subjects will need to live near that NIH since they will have to make frequent visits to the NIH campus.
Bruce   I like to hear that.  Travel is not in my capabilities.
chrisgrun   Yes, we are excited that it will be geographically spread out.
soapman1   Can anything be done to increase jaw strength having trouble chewing.
chrisgrun   it shoudl be helpful to look at teh results across several centers to see how robust the results are.
chrisgrun   I have heard some patients report improvement after doing chewing exercises.
BobK   Any sense of frequent visits, or too early to tell?
Bruce   Yes, chewing, jaw and throat exercises have been helpful for several of us with KD.
chrisgrun   the exercises can be provided by a speech/language therapist or a therapist doing swallow evaluation.
chrisgrun   The visits will likely be every one to two weeks for less than a day
soapman1   Good stuff thanks
chrisgrun   We should have updates also at the KDA meeting in the fall.
dean   What are the other locations?
chrisgrun   I will be there with Kurt, Angela, Alice, Carlo, and Laura. We are looking forward to attending.
BCPaul   Have gone the speech therapist route, viewing the barium swallow videos was very informative, I am not starting any exercise routine for that pending my involvement with the exercise trial in June
Bruce   We appreciate your involvement.
chrisgrun   I do not know what the locations are right now, this has not been decided.
chrisgrun   We will be starting this study in the fall if everything goes well this summer.
mattsenac   Chris do you have an email list we can join to keep us up on your studies?
Bruce   We like to see trials.  We might get lucky one of these times.
chrisgrun   Please contact Angela, if you are interested in the exercise study.!!
chrisgrun   yes, Angela maintains an e-mail list and it would be great to have you on it. Just let Angela know.
mattsenac   OK thx
chrisgrun   Yes, the trials have been progressing well. We need to have good biomarkers to know whether or not a drug is likely to be successful at an earlier time point. THis way we know whether or not it makes sence to continue.
chrisgrun   There are two different approaches.. either preventing the progression or building new muscle so that the patients are stronger than they were before.
chrisgrun   The ideal drug will be able to do both of these functions.
BobK   Is there a thought that muscle can be regained where it has been lost?
mattsenac   Oh we all pray for that "ideal" drug
chrisgrun   I think that our understaning of the disease and potential drugs has expanded tremendously and we will have more possibilities in the future.
Bruce   Chris, you have been a great guest.  We would love to have you back at some time.
chrisgrun   Yes, I think that the muscle can be regained, this is possible.
MikeG   preventing the progression is good enough for me!
Bruce   That would be wonderful!
BCPaul   tried to get a test for 8-OHdG, an oxidative stress biomarker locally, but they refused
MikeG   Chris, we really appreciate you taking the time to give us these updates today!!!  You have been very helpful and I hope there will be enough people interested in the exercise trial to complete the study now.
TomK   Good Presentation thank you chris!
BobK   That sounds very promising! Ditto what Bruce said - thank you Dr G!!
chrisgrun   Yes, we would be happy to prevent progression, but drugs that will increase muscle mass could produce even greater benefit.
chrisgrun   Sounds good. It has been great to do this and hear from  all of you.
MikeG   that would be our best hope!
chrisgrun   i would be happy to do this again sometime. just let me know.
MikeG   THANKS!!!
Bruce   Our thanks to you and all of the researchers at NIH.
Gary_KC   Thank you very much for nice chat.
Stewart   Thank you, This was very informative
chrisgrun   thankyou for having me. have a great weekend.
Alexandre   Thank you Dr. Chris, it was very hepful for all of us!!
UTE   Yes great info
MikeG   Take care and have a great weekend!
BobK   Good session. Thanks everyone. Have a good a weekend.

Topic:  Research Update

Guest:  Diane Merry, Ph.D.

Host:  Jameson Parker

-

Hugo Rodriguez   Good morning
CTjameson   Good morning!
CTjameson   You're both here early
Hugo Rodriguez   How do you doing CT?
Hugo Rodriguez   I always are confused with the chqange of time
CTjameson   Body is weak, but the spirits are high!
CTjameson   And you Hugo?
Hugo Rodriguez   Excellent!
CTjameson   Where are you from?
Hugo Rodriguez   I'm from Mexico. I already don't have meany troubles with the disease
Hugo Rodriguez   I suffer more with two disc lumbar hernias and the prostate
CTjameson   Sounds painful.
Hugo Rodriguez   Only sometimes, now is not bad at all
Hugo Rodriguez   next tuesday I have my first appointment with the neurosurgeon to see the possibilitu
Hugo Rodriguez   possibility of having a surgery
Hugo Rodriguez   From where are you CT?
CTjameson   How old are you and when were you diagnosed with KD?
CTjameson   Jameson is my name, CT is where I live.  CT is Connecticut.  I live near New York city is the USA.
Hugo Rodriguez   I'm 60. 5 years ago I was diagnosed with ALS and after was discarded for Kennedy's
Hugo Rodriguez   Thanks James, sorry for naming you CT
Hugo Rodriguez   The KD diagnosis was after the DNA test
Hugo Rodriguez   NOw, the genetis
Hugo Rodriguez   tthe genetist is trying to find, more relatives affected in my family
CTjameson   It is very common for people with KD to get an ALS diagnosis.  KD is not good, but it is much better than ALS!
Hugo Rodriguez   How early are we in the scheduled time for the chat?
CTjameson   It starts at 10:30.  I am hosting which is why I am here early
CTjameson   I am 39 and was diagnosed 6 years ago.
Hugo Rodriguez   You're right. The first diagnose got a lot of depression in my. Later I rev
CTjameson   Good morning Diane!
CTjameson   You are early :-)
Hugo Rodriguez   Later I recovered, before the right diagnosis
Hugo Rodriguez   Good mo
Hugo Rodriguez   Hello Diane!
Diane Merry   Sorry; I was just checking to see if I could get in.  I'm not quite ready anyway.  But now I can't figure out how to log out!  Obviously, I'm not savvy about chatting!
CTjameson   lol
CTjameson   You can just close the chat.  We'll see you in 20 minutes or so.
CTjameson   Hugo, Dr. Diane Merry is a researcher and long time friend of the KDA.  She will be sharing her research with us today.
Hugo Rodriguez   Thnak James, I read something about that in the messages we receive in the mail
Hugo Rodriguez   that IFG-1 is discarde, to cope with the KD?
Hugo Rodriguez   IGF-1 is right, it is not?
CTjameson   Yes, IGF-1 is right.  Dr. Merry has logged out and will be back at the start.
Hugo Rodriguez   Thanks again James, I just understand that
Hugo Rodriguez   What treatments have you tried James?
CTjameson   none
CTjameson   yet
Hugo Rodriguez   I have had Dutasteride for some weeks, not for KD but for benign prostatic hyperplasia
Hugo Rodriguez   Have you tried the smart exercises of the guide published at the KDA's pages?
CTjameson   not consistently.  You?
Hugo Rodriguez   Or the exercises of the clinic trial of the NIH at Bethesda?
Hugo Rodriguez   Actually not. Years ago I had
CTjameson   I have not.
Hugo Rodriguez   I had exercising my muscles at the gym, before knowing about my disease and that that could be harmful, but my wife told me that was beneficial
Hugo Rodriguez   Good morning Tom and Bruce.
Bruce   Morning everyone
david   Good Morning All
connie   good morning
TomK   Good Morning sorry if we interrupted your chat
Hugo Rodriguez   At this moment  I don't how much could be the exercise and after someone encouraged me to request to participate in the clinic trial of the NIH, finally I was accepted in the program.  I will fly to Bethesda next june.
Hugo Rodriguez   Not problem Tom. Happened that James and me started too early.
CTjameson   Good morning Tomk and david
CTjameson   Bruce, good morning
david   I am glad you will be able to particpate in the NIH trial
Bruce   Hey Jameson
CTjameson   That is excellent Hugo.  That must be a long trip.
Hugo Rodriguez   Thank you David, have you participated?
david   Yes my testing period was about a year ago and I found it challenging and rewarding.  I am still doing some of things they taught me and I look forward to reading about the results.
CTjameson   Excellent.  Thank you david.
TomK   Just started with a new Neurologist; does anybody know of Hani Kushlaf MD he just came off a fellowship from the MAYOa Clinic now teaching at the Univesitry of Cincinnati?
Hugo Rodriguez   Certainly Jameson, I found a cheap flight to Los Angeles (where a sister of me lives) and later I will fly to Washingtong
Gary_KC   Good morning! This is Gary. It was snow in May this year in Kansas City.
CTjameson   we'll hear about some of the results of the NIH trial on a chat June 1st.
david   Hi Gary
Bruce   Gary, my daughter and son, both in MN, said they had between 8 and 18" depending upon the location.
CTjameson   yikes.  I do not envy that.
Hugo Rodriguez   You are invited to come to Mexico
CTjameson   I suppose the only snow you see is in your freezer.
david   TomK, my nephew Michael's neurologist is also at UC Medical center but I cannot recall the name.  I will check with my sister later and let you know.
Bruce   Where do you live in Mexico?
Gary_KC   Hugo, sound good! I like warm country.
Hugo Rodriguez   I lñive in Queretro, at the center of the country
Hugo Rodriguez   Querataro is right, sorry for the mistake
TomK   Thanks David first visit was on April 23, seems Knowlwdgeable about kennedy's disease?
Bruce   I have been to a few border cities and also Mexico City
david   Hugo I had the opportunity to travel on business in Mexico City and Pueblo in the mid-1980s and enjoyed my time in your country
UTE   Kennedy's Disease Chat
CTjameson   Good morning Dr. Merry
Diane Merry   Good morning folks; I'm back now!  Good thing I started early, since i had to download some software to allow me to get into the chat.
Bruce   Thank you for taking the time to join us this morning
Hugo Rodriguez   I also have enjoyed the US (and the snow)
Diane Merry   That is, for those who don't know, I checked into the chat around 10 am - a bit early, but just making sure that i could get in!
Hugo Rodriguez   Welcome again to the chat, Diane
CTjameson   We are fortunate to have Dr. Diane Merry join us for today’s chat.   Today she will be giving us an update on current Kennedy's Disease research.  Doctor Merry is an Associate Professor at Thomas Jefferson University and a member of the KDA's Scientific Review Board.   She is also a longtime friend of the KDA.
Diane Merry   I hope everyone is doing well on this beautiful spring morning (at least it's beautiful here in Philadelphia!)
CTjameson   Perfect in Connecticut.
TomK   Nice day in Cincinnati also
Bruce   Rain in Georgia ... Snow in Minnesota
connie   Cloudy in Florida
CTjameson   Dianne, how long have you been in KD research?
Hugo Rodriguez   A little chilly in Queretaro (only chilli to mexicans)
david   It's a little cloudy in Cincinnati area but otherwise a typical spring morning
UTE   clear skies in slc
Diane Merry   Yes, thank you for asking me to join you today.  I'm happy to give some updates on research as well as tell you about the upcoming Gordon Conference that I am cochairing, and which the KDA is generously supporting.
Stewart   Good morning from SoCal
Bruce   We are all eyes (ears)
Diane Merry   I've been doing research on KD since I joined Kurt Fischbeck's lab as a postdoc in 1993.
Hugo Rodriguez   ymy que3stion is on the probable effectiveness of IGF-1
CTjameson   We are all excited to hear about what you are doing.
Diane Merry   Regarding Hugo's question about IGF-1, this is of course Dr. Fischbeck's work, and it is very interesting and exciting.  IGF-1 can effect muscle directly, and by improving muscle function can benefit neurons as well.  I think it is a smart direction to go.
Diane Merry   Shall I start off telling you about the Gordon Conference or about my research?
Bruce   Your choice
Hugo Rodriguez   also, I would like to know about the most harmful anesthesia during surgery. I have programmed a surgery for the end of june, for cope the benign prostatic hyperplasia
Diane Merry   Okay; becasue it's a more limited conversation, I'll tell you about the Gordon Conference first, and then we'll talk about research, since I'm sure you'll have more questions about that.
Bruce   Diane, some might not know what the Gordon Conference is all about.
Diane Merry   Probably best if I do short sentences.  Answering Hugo here - unfortuantely, Hugo, this is not my area of expertise, so I can't really give you information about anesthesia.
Bruce   Hugo, we have information on the KDA website that will be helpful.
Hugo Rodriguez   Thanks Bruce
Hugo Rodriguez   I'll see it.
Diane Merry   Good point  Bruce.  The Gordon Conference organization runs a LOT of small meetings throughout the year of very focused topics.  They are small, limited to about 150 - 200 scientists.  EVeryone is expected to stay for the entire time (5 days) and there is a lot of time for informal discussions.  Everything is "off the record".
Diane Merry   We started a Gordon Research Conference (GRC) on trinucleotide repeat diseases in 2001, and they have been held every two years since then.
Diane Merry   They focus on the CAG repeat disorders, KD being one of those, but also incorporate invited speakers on toher repeat diseases, since we can learn a lot from studying as well - diseases like myotonic dystrophy and fragile X syndrome.
Diane Merry   I was the chair of the GRC in 2007, when it was held in France, the co-chair in 2005 and now was invited to co-chair this one when the previous co-chair was unexpectedly unable to do it.
Diane Merry   It's a lot of work, but Leslie Thompson, the chair and an HD researcher, has done an excellent job at putting togehter a stellar slate of speakers, many of them in the KD field.
Ron M   Kennedy's Disease Chat
Diane Merry   For example, Kurt Fischbeck is speaking on the opening night, Al La Spada is a discussion leader, and Gen Sobue is the keynote speaker of the whole conference.
Bruce   A great lineup for KD related researchers
Hugo Rodriguez   Do you think that a report on my CAG repetitions could be usuful for you, Dr. Diane. I can send you a copy.
Diane Merry   Also, Andy Lieberman is a discussion leader at the meeting that precedes the GRC, which is for grad students and postdocs only.  It's a great addition to hte meeting and helps to get students and postddocs more engaged in discussions.
Diane Merry   Thank you very much, Hugo, for your kind offer to share that information.  At this time, however, I don't think it helps my research.  It may be improtant if you are involved in a clinical trial at some point, but I'm not sure that it is necessary then.
Bruce   For the group, Diane Merry, Kurt Fischbeck, Al La Spada and Andy Lieberman are members of the KDA's Scientific Review Board.
Hugo Rodriguez   You are welcome Diane.
Diane Merry   I should also say that the KDA has been generous in providing some support for registration for junior (students and post-docs) to attend hte meeting.  It's an expensive meeting, and the travel funds on NIH grants (and other) are really limiting scientist's involvement, so it s a HUGE help!
Diane Merry   The meeting this year is in Waterville Valley, New Hampshire, so it's expensive for scientists from Europe and Asia (and even the west coast and  Canada).  It's a great venue for sharing unpublished data - always helps to get scientists collaborating and sparks new ideas.  I'm excited to be a part of it.
CTjameson   We are excited to see so many excellent researchers involved!
Bruce   And for those of us living with KD, we are appreciative of all the researchers involvement.
Diane Merry   Yes, one of the good things about this meeting is that there is at least one of the 7 or so sessions completely devoted to therapeutics.  And the KDA researchers always have a round table meeting during one of the free afternoons.  It has become "famous" for always happening at the GRC meetings and several non-KD-focused researchers like to join as well.
CTjameson   We get to meet many of them at the KDA conferences, it is an excellent experience.
Hugo Rodriguez   Diane, years ago, before knowing I have KD, I was exercising my muscles (not too strongth) and getting some benefits. Later I knew that that could be harmful. I beleive that exist a critical point between this two states: beneficial-harmful.
Diane Merry   I say "round-table" but we usually have it outside under a tree somewhere!
CTjameson   lol
CTjameson   Diane, how many researchers focused on KD are attending?
Diane Merry   Yes, there is likely a balance between helpful and harmful exercise.  There are a lot of good reasons to exercise.
Diane Merry   I don't have the exact number of KD-focused scientists in front of me, but I think that it's about 15-20 or so of the current 120 or so attendees.  Students and post-docs from many of the KD-focused labs.
TomK   Diane are there any researchers on KD from the state of Ohio?
Diane Merry   Students coming when even the PIs cannot.  The KDA grant recipient from last year, Jamie Johansen, is attending.
Diane Merry   TomK, I think that there are, but am blanking on their names right now.  There have been some clinicians from Ohio involved in KD research.
Bruce   Diane, what is going on in your lab these days?
Bruce   And, did I hear some exciting news about Heather?
Diane Merry   Bruce and everyone, thanks - let me give you an update.  There are a few areas, several basic, some translational.
Diane Merry   And yes, Heather Montie, a postdoctoral fellow in my lab and a friend of the KDA and previous KDA grant awardee, has taken a faculty position at PCOM, Philadelphia College of Osteopathic Medicine.
Hugo Rodriguez   Diane, how much could be related my CPK levels and the damage produced to my muscles. My levels are between 1500 and 1800 without doing exercises.
Diane Merry   And as a reminder, the KDA award to Heather allowed her to generate preliminary data on the role of AR acetylation in KD (I'll explain that in a minute).  We published a paper on it in late 2011.  Her preliminary data also allowed us to get a small grant from the NIH to fund the creation of a new mouse model of KD, to test the role of this acetylation change in a mouse.  Now I'm working on getting more funding from the NIH to finish the characterization of the mice.
Diane Merry   Hugo, I'm so sorry that I'm not very good at the more clinically-relevant questions, since i myself am not a neurologist.  That might be a good question for your neurologist or for Dr. Fischbeck if you get him on a chat.
Hugo Rodriguez   Ploease don't mind. I understand.
Diane Merry   So we've been focusing on the androgen receptor protein itself, trying to understand how it misfolds in the cell, and specifically in the nucleus of the cell, where it needs to be to cause toxicity.
Diane Merry   We've found a couple of aspects of the androgen receptor protein that really seem to be important for toxicity and we're trying to fully validate those findings in mice (we have a LOT of new mouse lines right now) and to identify compounds that will help.
Bruce   Diane, would you take a moment and talk about the role of the AR (day job) and why it is a problem in those of us with KD?
Diane Merry   REgarding the acetylation project that I mentioned, acetyl groups are small chemical modifications that are attached to proteins and play a role in their function.  They are attached by enzymes and removed by enzymes.  We found that the "toxic" form of the androgen receptor in our KD models has more of these acetyl groups.  If we remove them by putting in more of the enzyme that removes them (that enzyme is called SIRT1), it protects motor neurons.
Hugo Rodriguez   Sounds promising
Diane Merry   Yes, thanks Bruce.  Let me back up a bit.  THe androgen receptor's "day job" is to bind to testosterone, move into the nucleus of the cell, and activate the expression of a lot of other genes.  It is called a transcription factor because it activates the transcription "transcribing" the information from DNA into RNA.
Diane Merry   There is some controversy about whether that "day job" is part of the disease process.  Data from my lab says that it is not.
Diane Merry   However, there are some aspects of the androgen receptor protein in KD that are different from normal androgen receptor.  One is that acetylation difference.  And just to mention where we are going with that work, we want to validate the effect in mice (that is Heather's work in my lab and she will continue to work on that in her new lab).  Also, I started a collaboration with a company "Sirtris" which is a part of GlaxoSmithKline, and now that is completely within GSK, to test compounds that they are developing to activate the enzyme, SIRT1, that removes acetyl groups from the AR.
Diane Merry   We've started testing these compounds in cell models and one of them looks promising.  We have a lot to do, but I am submitting a translational grant to the NIH this June to try to get major funding to really push this project forward.
CTjameson   what kind of company is Sirtris?
Bruce   So I gather we all have this enzyme?  Are we just not producing enough or does it take more with the defect?
Diane Merry   Sirtris was started by a group of scientists who were studying the effect of resveratrol (that's the compound that comes from the skin of red grapes) on various pathways.
Diane Merry   It was bought by GSK and now the work is completely within GSK.  I continue to collaborate with the group within GSK.
CTjameson   and what is a "translational" grant?
Diane Merry   Yes, great question, Bruce.  We all have this enzyme.  We're doing experiments now (even as we speak!) to determine whether the SIRT1 enzyme is deficient in KD neurons or whether the enzyme is fine but it just can't bind as well to the AR.
Bruce   Thanks, that is helpful.
Diane Merry   Jameson, a translational grant is a grant that focuses on a therapy.  No basic science about mechanisms.
Diane Merry   The goal of these translational grants is to move potential compounds into clinical trails.  The best compoudns with all of the right pharmacological characteristics.
Bruce   Would this be an oral medication?
Diane Merry   The NIH has finally realized that to do this correctly, these grants have to be properly funded, so the budgets for these grants are higher than usual.  We tried to work with one of these translational grants before but the budget just wasn't high enough to cover the expensive mouse work.
CTjameson   How do you recruit for clinical trials?  I bet you would have a few volunteers right here in this chat :)
Diane Merry   I'm not sure yet about delivery of the SIRT1-activating compounds, since we haven't started any of the mouse work yet.  I need to sit down with my GSK colleagues and talk about them more.  I do know that the compound that we are working iwth has good availability in the nervous system.
Bruce   So, it could be just needing something to open the valve a little more?
Diane Merry   Jameson, I myself am not doing clinical trials, since I am not a physician.  Dr. Fischbeck is the one who would do a clinical trial.  For the compounds that we are currently interested in, we would wait until we have mouse data, what we call "pre-clinical trial" and then discuss with him (and with the NIH for funding) to think about a trial.
Diane Merry   It's wonderful that many of you have been interested in and so helpful with volunteering for clinical trials.
Diane Merry   Yes, Bruce, we think that removing these acetyl groups somehow prevents the AR from misfolding and aggregating.  We've been working on new ways to analyze the misfolding and we can see that this is true.
Bruce   Thanks
CTjameson   With five minutes left, are there any questions for Dr. Merry concerning the research that happens in her lab?
connie   Could you please give us a time line about the mouse trials before we even get to the clinical trials?
Diane Merry   The other area of therapy development that we're working on is with AR ligands (like testosterone)), both that activate or inhibit the activity, as potential therapeutics.  We know that bicalutamide (casodex) is protective, and we are now testing a newly FDA-approved for prostate cancer, compound called Xtandia (enzalutamide).
Diane Merry   We have some promising results in motor neurons in a dish.  We need a bit more validation and then we'll start testing mice.  This is a project htat Lori Cooper, a student in my lab, is working on.
Bruce   I know this research takes time and we appreciate your labs continued focus and involvement.
Diane Merry   Yes, Connie, the funding for the mouse trials should take 6 months to a year to obtain.  Then the mouse work takes about a year, maybe two.  There are pilot studies for dosing and delivery mehtods, for example.
Diane Merry   The good thing about the new compound, Xtandia, is that we know that it gets into the brain.  This is better than the previous, similar compound, Casodex, which doesnt get into the nervous system very well.
CTjameson   Over the course of your 20 years researching KD, how many mouse trials would you estimate you have done?
Diane Merry   The other thing that we are doing is useing, not only our mouse model for testing, but Andy Lieberman's mouse model as well.  This gets at effects in muscle.
Bruce   That is great to test both models.
Diane Merry   I have really only done two mouse trials, one with Dutasteride, and one more recently with Bicalutamide (Casodex).  We've done lots of "genetic" trials, that is to test hypotheses about mechanism.
Diane Merry   Yes, Andy and I agree that there is real power to this, since one tests the motor neuron effects while the other tests muscle effects.  I am keeping fingers crossed for the NIH funding!
Bruce   Diane, thank you so much for participating today.  We appreciate all that you do for those of us living with KD and for the KDA.
CTjameson   Thank you for you time Dr. Merry.  You expertise and time you've invested help to cure this disease is most appreciated.
UTE   do u interact with Andy and Jamie quite a bit as u move forward
CTjameson   We are all thankful
Gary_KC   Diane, thank you very much for your time this moring.
Hugo Rodriguez   Thanks for being with us Dr. Merry, we wish you a lot of success!
UTE   Very eye opening...tk u
Diane Merry   Thank you so much for having me.  I've enjoyed chatting wiht you all.  Yes, I interact a lot iwth Andy Lieberman, not as much with Jamie, though I am very supportive of her work.  Hopefully I can give you promising updates not too far in the future, certainly at the KDA meeting in the fall!
connie   Thank you. Best of luck.
Diane Merry   Take care everyone.  You are always in my thoughts.
Bruce   We appreciate that ...
Bruce   Say HELLO to Heather
Diane Merry   I don't want to drop off too soon.  Any last questions?
Hugo Rodriguez   No from me
Diane Merry   I will certainly say hello to Heather for you!  I am thrilled that she will be starting in her own lab.  She is an outstanding scientist!
UTE   tks again
david   Thank you this has been very informative
Hugo Rodriguez   Thanks for all
Diane Merry   Great; thanks again and I will say good bye now!  Best to all of you!
Hugo Rodriguez   bye everybody
CTjameson   Have a great day all!
Gary_KC   Bye all.

 

Hugo Rodriguez   Good morning
CTjameson   Good morning!
CTjameson   You're both here early
Hugo Rodriguez   How do you doing CT?
Hugo Rodriguez   I always are confused with the chqange of time
CTjameson   Body is weak, but the spirits are high!
CTjameson   And you Hugo?
Hugo Rodriguez   Excellent!
CTjameson   Where are you from?
Hugo Rodriguez   I'm from Mexico. I already don't have meany troubles with the disease
Hugo Rodriguez   I suffer more with two disc lumbar hernias and the prostate
CTjameson   Sounds painful.
Hugo Rodriguez   Only sometimes, now is not bad at all
Hugo Rodriguez   next tuesday I have my first appointment with the neurosurgeon to see the possibilitu
Hugo Rodriguez   possibility of having a surgery
Hugo Rodriguez   From where are you CT?
CTjameson   How old are you and when were you diagnosed with KD?
CTjameson   Jameson is my name, CT is where I live. CT is Connecticut. I live near New York city is the USA.
Hugo Rodriguez   I'm 60. 5 years ago I was diagnosed with ALS and after was discarded for Kennedy's
Hugo Rodriguez   Thanks James, sorry for naming you CT
Hugo Rodriguez   The KD diagnosis was after the DNA test
Hugo Rodriguez   NOw, the genetis
Hugo Rodriguez   tthe genetist is trying to find, more relatives affected in my family
CTjameson   It is very common for people with KD to get an ALS diagnosis. KD is not good, but it is much better than ALS!
Hugo Rodriguez   How early are we in the scheduled time for the chat?
CTjameson   It starts at 10:30. I am hosting which is why I am here early
CTjameson   I am 39 and was diagnosed 6 years ago.
Hugo Rodriguez   You're right. The first diagnose got a lot of depression in my. Later I rev
CTjameson   Good morning Diane!
CTjameson   You are early :-)
Hugo Rodriguez   Later I recovered, before the right diagnosis
Hugo Rodriguez   Good mo
Hugo Rodriguez   Hello Diane!
Diane Merry   Sorry; I was just checking to see if I could get in. I'm not quite ready anyway. But now I can't figure out how to log out! Obviously, I'm not savvy about chatting!
CTjameson   lol
CTjameson   You can just close the chat. We'll see you in 20 minutes or so.
CTjameson   Hugo, Dr. Diane Merry is a researcher and long time friend of the KDA. She will be sharing her research with us today.
Hugo Rodriguez   Thnak James, I read something about that in the messages we receive in the mail
Hugo Rodriguez   that IFG-1 is discarde, to cope with the KD?
Hugo Rodriguez   IGF-1 is right, it is not?
CTjameson   Yes, IGF-1 is right. Dr. Merry has logged out and will be back at the start.
Hugo Rodriguez   Thanks again James, I just understand that
Hugo Rodriguez   What treatments have you tried James?
CTjameson   none
CTjameson   yet
Hugo Rodriguez   I have had Dutasteride for some weeks, not for KD but for benign prostatic hyperplasia
Hugo Rodriguez   Have you tried the smart exercises of the guide published at the KDA's pages?
CTjameson   not consistently. You?
Hugo Rodriguez   Or the exercises of the clinic trial of the NIH at Bethesda?
Hugo Rodriguez   Actually not. Years ago I had
CTjameson   I have not.
Hugo Rodriguez   I had exercising my muscles at the gym, before knowing about my disease and that that could be harmful, but my wife told me that was beneficial
Hugo Rodriguez   Good morning Tom and Bruce.
Bruce   Morning everyone
david   Good Morning All
connie   good morning
TomK   Good Morning sorry if we interrupted your chat
Hugo Rodriguez   At this moment I don't how much could be the exercise and after someone encouraged me to request to participate in the clinic trial of the NIH, finally I was accepted in the program. I will fly to Bethesda next june.
Hugo Rodriguez   Not problem Tom. Happened that James and me started too early.
CTjameson   Good morning Tomk and david
CTjameson   Bruce, good morning
david   I am glad you will be able to particpate in the NIH trial
Bruce   Hey Jameson
CTjameson   That is excellent Hugo. That must be a long trip.
Hugo Rodriguez   Thank you David, have you participated?
david   Yes my testing period was about a year ago and I found it challenging and rewarding. I am still doing some of things they taught me and I look forward to reading about the results.
CTjameson   Excellent. Thank you david.
TomK   Just started with a new Neurologist; does anybody know of Hani Kushlaf MD he just came off a fellowship from the MAYOa Clinic now teaching at the Univesitry of Cincinnati?
Hugo Rodriguez   Certainly Jameson, I found a cheap flight to Los Angeles (where a sister of me lives) and later I will fly to Washingtong
Gary_KC   Good morning! This is Gary. It was snow in May this year in Kansas City.
CTjameson   we'll hear about some of the results of the NIH trial on a chat June 1st.
david   Hi Gary
Bruce   Gary, my daughter and son, both in MN, said they had between 8 and 18" depending upon the location.
CTjameson   yikes. I do not envy that.
Hugo Rodriguez   You are invited to come to Mexico
CTjameson   I suppose the only snow you see is in your freezer.
david   TomK, my nephew Michael's neurologist is also at UC Medical center but I cannot recall the name. I will check with my sister later and let you know.
Bruce   Where do you live in Mexico?
Gary_KC   Hugo, sound good! I like warm country.
Hugo Rodriguez   I lñive in Queretro, at the center of the country
Hugo Rodriguez   Querataro is right, sorry for the mistake
TomK   Thanks David first visit was on April 23, seems Knowlwdgeable about kennedy's disease?
Bruce   I have been to a few border cities and also Mexico City
david   Hugo I had the opportunity to travel on business in Mexico City and Pueblo in the mid-1980s and enjoyed my time in your country
UTE   Kennedy's Disease Chat
CTjameson   Good morning Dr. Merry
Diane Merry   Good morning folks; I'm back now! Good thing I started early, since i had to download some software to allow me to get into the chat.
Bruce   Thank you for taking the time to join us this morning
Hugo Rodriguez   I also have enjoyed the US (and the snow)
Diane Merry   That is, for those who don't know, I checked into the chat around 10 am - a bit early, but just making sure that i could get in!
Hugo Rodriguez   Welcome again to the chat, Diane
CTjameson   We are fortunate to have Dr. Diane Merry join us for today’s chat. Today she will be giving us an update on current Kennedy's Disease research. Doctor Merry is an Associate Professor at Thomas Jefferson University and a member of the KDA's Scientific Review Board. She is also a longtime friend of the KDA.
Diane Merry   I hope everyone is doing well on this beautiful spring morning (at least it's beautiful here in Philadelphia!)
CTjameson   Perfect in Connecticut.
TomK   Nice day in Cincinnati also
Bruce   Rain in Georgia ... Snow in Minnesota
connie   Cloudy in Florida
CTjameson   Dianne, how long have you been in KD research?
Hugo Rodriguez   A little chilly in Queretaro (only chilli to mexicans)
david   It's a little cloudy in Cincinnati area but otherwise a typical spring morning
UTE   clear skies in slc
Diane Merry   Yes, thank you for asking me to join you today. I'm happy to give some updates on research as well as tell you about the upcoming Gordon Conference that I am cochairing, and which the KDA is generously supporting.
Stewart   Good morning from SoCal
Bruce   We are all eyes (ears)
Diane Merry   I've been doing research on KD since I joined Kurt Fischbeck's lab as a postdoc in 1993.
Hugo Rodriguez   ymy que3stion is on the probable effectiveness of IGF-1
CTjameson   We are all excited to hear about what you are doing.
Diane Merry   Regarding Hugo's question about IGF-1, this is of course Dr. Fischbeck's work, and it is very interesting and exciting. IGF-1 can effect muscle directly, and by improving muscle function can benefit neurons as well. I think it is a smart direction to go.
Diane Merry   Shall I start off telling you about the Gordon Conference or about my research?
Bruce   Your choice
Hugo Rodriguez   also, I would like to know about the most harmful anesthesia during surgery. I have programmed a surgery for the end of june, for cope the benign prostatic hyperplasia
Diane Merry   Okay; becasue it's a more limited conversation, I'll tell you about the Gordon Conference first, and then we'll talk about research, since I'm sure you'll have more questions about that.
Bruce   Diane, some might not know what the Gordon Conference is all about.
Diane Merry   Probably best if I do short sentences. Answering Hugo here - unfortuantely, Hugo, this is not my area of expertise, so I can't really give you information about anesthesia.
Bruce   Hugo, we have information on the KDA website that will be helpful.
Hugo Rodriguez   Thanks Bruce
Hugo Rodriguez   I'll see it.
Diane Merry   Good point Bruce. The Gordon Conference organization runs a LOT of small meetings throughout the year of very focused topics. They are small, limited to about 150 - 200 scientists. EVeryone is expected to stay for the entire time (5 days) and there is a lot of time for informal discussions. Everything is "off the record".
Diane Merry   We started a Gordon Research Conference (GRC) on trinucleotide repeat diseases in 2001, and they have been held every two years since then.
Diane Merry   They focus on the CAG repeat disorders, KD being one of those, but also incorporate invited speakers on toher repeat diseases, since we can learn a lot from studying as well - diseases like myotonic dystrophy and fragile X syndrome.
Diane Merry   I was the chair of the GRC in 2007, when it was held in France, the co-chair in 2005 and now was invited to co-chair this one when the previous co-chair was unexpectedly unable to do it.
Diane Merry   It's a lot of work, but Leslie Thompson, the chair and an HD researcher, has done an excellent job at putting togehter a stellar slate of speakers, many of them in the KD field.
Ron M   Kennedy's Disease Chat
Diane Merry   For example, Kurt Fischbeck is speaking on the opening night, Al La Spada is a discussion leader, and Gen Sobue is the keynote speaker of the whole conference.
Bruce   A great lineup for KD related researchers
Hugo Rodriguez   Do you think that a report on my CAG repetitions could be usuful for you, Dr. Diane. I can send you a copy.
Diane Merry   Also, Andy Lieberman is a discussion leader at the meeting that precedes the GRC, which is for grad students and postdocs only. It's a great addition to hte meeting and helps to get students and postddocs more engaged in discussions.
Diane Merry   Thank you very much, Hugo, for your kind offer to share that information. At this time, however, I don't think it helps my research. It may be improtant if you are involved in a clinical trial at some point, but I'm not sure that it is necessary then.
Bruce   For the group, Diane Merry, Kurt Fischbeck, Al La Spada and Andy Lieberman are members of the KDA's Scientific Review Board.
Hugo Rodriguez   You are welcome Diane.
Diane Merry   I should also say that the KDA has been generous in providing some support for registration for junior (students and post-docs) to attend hte meeting. It's an expensive meeting, and the travel funds on NIH grants (and other) are really limiting scientist's involvement, so it s a HUGE help!
Diane Merry   The meeting this year is in Waterville Valley, New Hampshire, so it's expensive for scientists from Europe and Asia (and even the west coast and Canada). It's a great venue for sharing unpublished data - always helps to get scientists collaborating and sparks new ideas. I'm excited to be a part of it.
CTjameson   We are excited to see so many excellent researchers involved!
Bruce   And for those of us living with KD, we are appreciative of all the researchers involvement.
Diane Merry   Yes, one of the good things about this meeting is that there is at least one of the 7 or so sessions completely devoted to therapeutics. And the KDA researchers always have a round table meeting during one of the free afternoons. It has become "famous" for always happening at the GRC meetings and several non-KD-focused researchers like to join as well.
CTjameson   We get to meet many of them at the KDA conferences, it is an excellent experience.
Hugo Rodriguez   Diane, years ago, before knowing I have KD, I was exercising my muscles (not too strongth) and getting some benefits. Later I knew that that could be harmful. I beleive that exist a critical point between this two states: beneficial-harmful.
Diane Merry   I say "round-table" but we usually have it outside under a tree somewhere!
CTjameson   lol
CTjameson   Diane, how many researchers focused on KD are attending?
Diane Merry   Yes, there is likely a balance between helpful and harmful exercise. There are a lot of good reasons to exercise.
Diane Merry   I don't have the exact number of KD-focused scientists in front of me, but I think that it's about 15-20 or so of the current 120 or so attendees. Students and post-docs from many of the KD-focused labs.
TomK   Diane are there any researchers on KD from the state of Ohio?
Diane Merry   Students coming when even the PIs cannot. The KDA grant recipient from last year, Jamie Johansen, is attending.
Diane Merry   TomK, I think that there are, but am blanking on their names right now. There have been some clinicians from Ohio involved in KD research.
Bruce   Diane, what is going on in your lab these days?
Bruce   And, did I hear some exciting news about Heather?
Diane Merry   Bruce and everyone, thanks - let me give you an update. There are a few areas, several basic, some translational.
Diane Merry   And yes, Heather Montie, a postdoctoral fellow in my lab and a friend of the KDA and previous KDA grant awardee, has taken a faculty position at PCOM, Philadelphia College of Osteopathic Medicine.
Hugo Rodriguez   Diane, how much could be related my CPK levels and the damage produced to my muscles. My levels are between 1500 and 1800 without doing exercises.
Diane Merry   And as a reminder, the KDA award to Heather allowed her to generate preliminary data on the role of AR acetylation in KD (I'll explain that in a minute). We published a paper on it in late 2011. Her preliminary data also allowed us to get a small grant from the NIH to fund the creation of a new mouse model of KD, to test the role of this acetylation change in a mouse. Now I'm working on getting more funding from the NIH to finish the characterization of the mice.
Diane Merry   Hugo, I'm so sorry that I'm not very good at the more clinically-relevant questions, since i myself am not a neurologist. That might be a good question for your neurologist or for Dr. Fischbeck if you get him on a chat.
Hugo Rodriguez   Ploease don't mind. I understand.
Diane Merry   So we've been focusing on the androgen receptor protein itself, trying to understand how it misfolds in the cell, and specifically in the nucleus of the cell, where it needs to be to cause toxicity.
Diane Merry   We've found a couple of aspects of the androgen receptor protein that really seem to be important for toxicity and we're trying to fully validate those findings in mice (we have a LOT of new mouse lines right now) and to identify compounds that will help.
Bruce   Diane, would you take a moment and talk about the role of the AR (day job) and why it is a problem in those of us with KD?
Diane Merry   REgarding the acetylation project that I mentioned, acetyl groups are small chemical modifications that are attached to proteins and play a role in their function. They are attached by enzymes and removed by enzymes. We found that the "toxic" form of the androgen receptor in our KD models has more of these acetyl groups. If we remove them by putting in more of the enzyme that removes them (that enzyme is called SIRT1), it protects motor neurons.
Hugo Rodriguez   Sounds promising
Diane Merry   Yes, thanks Bruce. Let me back up a bit. THe androgen receptor's "day job" is to bind to testosterone, move into the nucleus of the cell, and activate the expression of a lot of other genes. It is called a transcription factor because it activates the transcription "transcribing" the information from DNA into RNA.
Diane Merry   There is some controversy about whether that "day job" is part of the disease process. Data from my lab says that it is not.
Diane Merry   However, there are some aspects of the androgen receptor protein in KD that are different from normal androgen receptor. One is that acetylation difference. And just to mention where we are going with that work, we want to validate the effect in mice (that is Heather's work in my lab and she will continue to work on that in her new lab). Also, I started a collaboration with a company "Sirtris" which is a part of GlaxoSmithKline, and now that is completely within GSK, to test compounds that they are developing to activate the enzyme, SIRT1, that removes acetyl groups from the AR.
Diane Merry   We've started testing these compounds in cell models and one of them looks promising. We have a lot to do, but I am submitting a translational grant to the NIH this June to try to get major funding to really push this project forward.
CTjameson   what kind of company is Sirtris?
Bruce   So I gather we all have this enzyme? Are we just not producing enough or does it take more with the defect?
Diane Merry   Sirtris was started by a group of scientists who were studying the effect of resveratrol (that's the compound that comes from the skin of red grapes) on various pathways.
Diane Merry   It was bought by GSK and now the work is completely within GSK. I continue to collaborate with the group within GSK.
CTjameson   and what is a "translational" grant?
Diane Merry   Yes, great question, Bruce. We all have this enzyme. We're doing experiments now (even as we speak!) to determine whether the SIRT1 enzyme is deficient in KD neurons or whether the enzyme is fine but it just can't bind as well to the AR.
Bruce   Thanks, that is helpful.
Diane Merry   Jameson, a translational grant is a grant that focuses on a therapy. No basic science about mechanisms.
Diane Merry   The goal of these translational grants is to move potential compounds into clinical trails. The best compoudns with all of the right pharmacological characteristics.
Bruce   Would this be an oral medication?
Diane Merry   The NIH has finally realized that to do this correctly, these grants have to be properly funded, so the budgets for these grants are higher than usual. We tried to work with one of these translational grants before but the budget just wasn't high enough to cover the expensive mouse work.
CTjameson   How do you recruit for clinical trials? I bet you would have a few volunteers right here in this chat :)
Diane Merry   I'm not sure yet about delivery of the SIRT1-activating compounds, since we haven't started any of the mouse work yet. I need to sit down with my GSK colleagues and talk about them more. I do know that the compound that we are working iwth has good availability in the nervous system.
Bruce   So, it could be just needing something to open the valve a little more?
Diane Merry   Jameson, I myself am not doing clinical trials, since I am not a physician. Dr. Fischbeck is the one who would do a clinical trial. For the compounds that we are currently interested in, we would wait until we have mouse data, what we call "pre-clinical trial" and then discuss with him (and with the NIH for funding) to think about a trial.
Diane Merry   It's wonderful that many of you have been interested in and so helpful with volunteering for clinical trials.
Diane Merry   Yes, Bruce, we think that removing these acetyl groups somehow prevents the AR from misfolding and aggregating. We've been working on new ways to analyze the misfolding and we can see that this is true.
Bruce   Thanks
CTjameson   With five minutes left, are there any questions for Dr. Merry concerning the research that happens in her lab?
connie   Could you please give us a time line about the mouse trials before we even get to the clinical trials?
Diane Merry   The other area of therapy development that we're working on is with AR ligands (like testosterone)), both that activate or inhibit the activity, as potential therapeutics. We know that bicalutamide (casodex) is protective, and we are now testing a newly FDA-approved for prostate cancer, compound called Xtandia (enzalutamide).
Diane Merry   We have some promising results in motor neurons in a dish. We need a bit more validation and then we'll start testing mice. This is a project htat Lori Cooper, a student in my lab, is working on.
Bruce   I know this research takes time and we appreciate your labs continued focus and involvement.
Diane Merry   Yes, Connie, the funding for the mouse trials should take 6 months to a year to obtain. Then the mouse work takes about a year, maybe two. There are pilot studies for dosing and delivery mehtods, for example.
Diane Merry   The good thing about the new compound, Xtandia, is that we know that it gets into the brain. This is better than the previous, similar compound, Casodex, which doesnt get into the nervous system very well.
CTjameson   Over the course of your 20 years researching KD, how many mouse trials would you estimate you have done?
Diane Merry   The other thing that we are doing is useing, not only our mouse model for testing, but Andy Lieberman's mouse model as well. This gets at effects in muscle.
Bruce   That is great to test both models.
Diane Merry   I have really only done two mouse trials, one with Dutasteride, and one more recently with Bicalutamide (Casodex). We've done lots of "genetic" trials, that is to test hypotheses about mechanism.
Diane Merry   Yes, Andy and I agree that there is real power to this, since one tests the motor neuron effects while the other tests muscle effects. I am keeping fingers crossed for the NIH funding!
Bruce   Diane, thank you so much for participating today. We appreciate all that you do for those of us living with KD and for the KDA.
CTjameson   Thank you for you time Dr. Merry. You expertise and time you've invested help to cure this disease is most appreciated.
UTE   do u interact with Andy and Jamie quite a bit as u move forward
CTjameson   We are all thankful
Gary_KC   Diane, thank you very much for your time this moring.
Hugo Rodriguez   Thanks for being with us Dr. Merry, we wish you a lot of success!
UTE   Very eye opening...tk u
Diane Merry   Thank you so much for having me. I've enjoyed chatting wiht you all. Yes, I interact a lot iwth Andy Lieberman, not as much with Jamie, though I am very supportive of her work. Hopefully I can give you promising updates not too far in the future, certainly at the KDA meeting in the fall!
connie   Thank you. Best of luck.
Diane Merry   Take care everyone. You are always in my thoughts.
Bruce   We appreciate that ...
Bruce   Say HELLO to Heather
Diane Merry   I don't want to drop off too soon. Any last questions?
Hugo Rodriguez   No from me
Diane Merry   I will certainly say hello to Heather for you! I am thrilled that she will be starting in her own lab. She is an outstanding scientist!
UTE   tks again
david   Thank you this has been very informative
Hugo Rodriguez   Thanks for all
Diane Merry   Great; thanks again and I will say good bye now! Best to all of you!
Hugo Rodriguez   bye everybody
CTjameson   Have a great day all!
Gary_KC   Bye all.