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Archives - 2015 and Older Transcripts

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.