Kennedy's Disease Association

A Public Benefit, Non-Profit Organization

"The KDA web site is a source of real information and even stories of other guys with the same problem. All of a sudden I was not alone, and also the information about the research going on gave me hope."

KDA Services

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.