Terryw entered the room.

LouLou entered the room.

Terryw: hi

Terryw: did not know if I was going to make it in here today

Terryw: been so dang busy

Bob-B entered the room.

Terryw: Hi Bob

LouLou: Hi Guys. How are you both doing? It is great to have Dr. Merry on board today.

UandS entered the room.

LouLou: Hi Bob. Where are you located.

Bob-B: North Carolina

LouLou: Stay DRY.

murf: Morning I was on the throne

LouLou: Hi U&S where are you located?

UandS: California

Terryw: Calif

Terryw: where in Calif

LouLou: Bob--do you have Kennedy's?--U&S do you have Kennedy's?

UandS: Husband does

Terryw: I am North of Fresno by Yosemite

Terryw: Fresno

Terryw: Fingers not working to well

UandS: Palm Desert today

Bob-B: Yes, I have KD, diagnosed in ~1986.

Terryw: ok

Terryw: Murf , how you been?

LouLou: Murf--what time is Dr. Merry joining us?

murf: Busy, Just got back from a visit to NIH on Monday

Terryw: have not heard from you in a while

murf: Ron- any time

MikeG entered the room.

Terryw: hi mike

MikeG: hi terry

murf: Morning Mike

MikeG: morning murray

LouLou: How was your trip to NIH and what did you find out?

Terryw: hi ron

LouLou: Hi Mike.

murf: Coffee is boiling ..One minute

MikeG: hi lou

Terryw: Been Crazy here Susanne was out of town for a week, she comes home today

MikeG: I'm on my 4th cup Murray

murf: Got it

MikeG: It's tough when your spouse goes out of town, isn't it?

murf: Those people at NIH are so nice it's unbelievable

Dr__M_ entered the room.

LouLou: Terry--I thought once she got some more help at work things would slow down for her.

Terryw: She did get a 2nd assistant

Terryw: that allowed her to travel now LOL

Dr__M_: Good morning everyone.

LouLou: Hi Dr. Merry.

Terryw: Hi

Dr__M_: Am I too early?

murf: Morning Dr. Merry

LouLou: NO right on time.

UandS: Good morning, Dr. Merry

Bob-B: Welcome

murf: Perfict timing!!

LouLou: Murf--what did they do for you or what could they tell you?

murf: We'll start the chat now...

Terryw: Dr. Merry what's been going on in your lab lately?

Bob-B: Dr. Merry, can you also tell us about the progress of your work with dutasteride?

LouLou: Murf--did you start the chat?

murf: Not much more than I did know already but they have another piece for the data base

murf: Ron - Yes

Gary_KS entered the room.

murf: Morning Gary

Gary_KS: Good morning! It is a nice sunny day in Kansas City.

Chuck entered the room.

Gary_KS: Good morning, Murf!

Dr__M_: We have a number of projects underway. Some projects, as you know, are designed to test new therapies in our mouse model. Other projects are designed to get at details of the disease process so that we can design effective therapies based on that knowledge.

LouLou: Hi Anna Lea and Chuck.

Michael17860 entered the room.

Michael17860: Hi All

murf: Morning Michael

LouLou: Dr. Merry--What help do you get from MDA as financial assistance?

Coak entered the room.

Terryw: Dr Merry did you see the following article published last week - A chemical compound has been found that prevents a neuron-degeneration process that destroys nerve cells and can lead to the gradual loss of the use of hands and feet, a group of researchers said. The findings of the research conducted by a team from the Nagoya University Graduate School of Medicine appear in the latest issue of the U.S. medical journal Nature Medicine. www.asahi.com

Terryw: directly related to SBMA

Terryw: n an experiment, laboratory mice genetically modified to possess spinal and bulbar muscular atrophy, one form of the motor neuron degeneration, were injected with 17-AAG.

murf: Morning John - good party!

Terryw: Hi John

Coak: Hi all. Thanks Murf-Great that you came up.

Chuck: Hi Ron -missed you and family at Hoe Down. Everyone enjoyed so much.

LouLou: Hi John C. Did you get everyone out of the pond?

Coak: 10-4

Terryw: Here is the link to the article. I will also be putting it on the research new page of the website http://www.asahi.com/english/Herald-asahi/TKY200509130229.html

denny entered the room.

Coak: Yard will be back to "normal" after my son comes over this afternoon.

murf: Thanks Terry

Terryw: don't click on it now or ir will kick you out of chat

Terryw: While Dr. Merry writes her response I have a question for all you KDers. Do any of your mothers have symptoms of KD?

murf: TJ is still in Bethesda with Dr.Chen and Alison

Dr__M_: Dutasteride, as you know, is a drug that inhibits the enzymes that convert testosterone (T) to its more potent form dihydrotestosterone (DHT). We've been testing it in our mice. The difficulty with mice, as you can imagine, is that we can't get them to take a pill or swallow a liquid easily. So figuring out the best delivery method is often the biggest hurdle, especially given the chemical characteristics of different drugs. We did a trial with dutasteride, but found that the drug wasn't effective, DUE THE WAY IN WHICH WE WERE DELIVERING IT (PUMPS) , in inhibiting the enzyme. We have just started a ew trial delivering the drug by injection. The mice have only been on it for 2 months. We don't see an effect yet, but we don't know the DHT levels yet (waiting for t

Dr__M_: Sorry; perhaps I'm writing so much that it takes a long time to send. So we don't have the DHT measurements back yet, and thus it's difficult to know how well the drug is working. We're taking the study out 6 months, so we still have some time.

murf: I guess we don't think of things like how to tell a mouse to take his pills on time

Coak: Diane, you need to sugar coat those mouse pills.

Dr__M_: Ok, I've figured out how to make it go faster. To answer your question, Terry, I didn't see the paper yet (just back and catching up with the growing lab), but I'm familiar with the study, if it's what I think it is. The 17-AAG I believe is also called geranygeranylacetone. The group reported results at several meetings recently. It works by helping neurons to get rid of the bad protein. It looks pretty good in their study. We haven't tried it in our mice, although we are testing other compounds that work in a similar way, to help the cells get rid of the protein.

Terryw: Great

LouLou: Dr, Merry, Is there anything you might tell us that might make things easier for us with KD? Any new drugs for cramping or twitching, etc. I have been having trouble with my eating and swallowing lately.

Terryw: Same here ron, I have to frink now with almost every bite

Dr__M_: To answer the question about MDA funding, yes, the MDA has been extremely supportive of our work for over 10 years. They are now supporting the therapeutic efforts of the lab, and I've just submitted a new grant to continue this work with their help.

Terryw: drink

kelly entered the room.

murf: Morning Kelly

Coak: This is a quiet bunch this AM. Are everyone's fingers broken

kelly: good morning murf.

kelly: //1

murf: Every one is all ears maybe. LOL

LouLou: Dr. M--glad to hear that you receive support from MDA. Jerry and his kids do a fabulous job.

MikeG: Ron, Terry - are you guys taking Neurontin or Gabapentin?

Terryw: Not me

LouLou: I take naproxen.

Dr__M_: Unfortunately, since I am not a neurologist, I don't have much information on drugs to help specific symptoms. Dr. Fischbeck would be the best to answer that question (or your neurologist). But I can say that with the various drugs that we are testing, or planning to test, we are mainly testing effects on strength. If we find something effective, we can then look at other symptoms, although it;s tough to study cramping in the mice.

Michael17860: Dr. Merry, Please tell Dr. Arnaudo that Mike Gill has asked about her.Thank You

kelly: here in sask my Dr. gave me CLOBAZAM.&CLONAZIPAM for the cramp's

Dr__M_: My lab is currently focusing on two types of drugs, those that affect testosterone/DHT or their binding to the androgen receptor, and those that we think will help the cell to get rid of the mutnat protein.

LouLou: I think we all could use more stregnth. Most times when we fall--if we had more stregnth, we could keep from falling.

murf: The NIH are planning to do the clinical study around Q4 2005 / Q1 2006, do you know what drug they will try?

Coak: For what it's worth -- I've taken Quinine Sulfate 325 mg daily for the last 40 years. It really helps with the cramping & I don't have many problems with that.

Dr__M_: Hi MIke, I will certainly do that. Dr. Arnaudo is about to start working with us to do EMG studies on our mice. This will help us to understand the disease better and how various drugs that we are testing are effecting nerve function.

Terryw: John I now found out that Quinine sulfate is no longer available over the counter. By perscription only here in Calif

MikeG: Come to think of it John, my mother takes Quinine Sulfate and it really helps her too!

kelly: I have tried quinine to.

Coak: Same here in MD -- It looks like cocaine powder. Rx is ez to get from MD.

MikeG: Yes you'll need a perscription for it.

Dr__M_: The only NIH trial that I know of for KD is the one that Dr. Fischbeck's group is planning with dutasteride (Avodart).

UandS: Dr. Merry, is dutasteride similar to finasteride?

murf: That's it

UandS: OK, thanks

Dr__M_: Yes, finasteride blocks on of the enzymes (5 alpha reductase type II) that converts testosterone to dihydrotestosterone, while dutasteride blocks both enzymes (types 1 and II).

murf: I hope I don't get sugar

LouLou: Murf--you are sweet enough already. LOL

Dr__M_: Dutasteride is currently used to treat benign prostatic hypertrophy, and it is in clinical trial for prostate cancer.

murf: Thanks Ron...I love you too bud

UandS: Dr. Merry, have you been able to uncover any new aspects of the disease process?

Coak: The NIH trial is planned for Q4 of '05 or Q1 of '06 with Dutasteride. Dr. Chen & Fischbeck are going to conduct the study.

murf: Very good questions this morning

kelly: Dr._M what's your profession? dr, fishbeck assitant?

Dr__M_: Yes, we have been studying what happens to the androgen receptor (AR) once it binds hormone. We know that hormone binding sends it into the nucleus, causing it to bind DNA. We have found that if we keep it from going into the nucleus (through a genetic manipulation), the cell can get rid of it faster. We're now trying to figure out what's different between the two compartments of the cell in the way that they can degrade the mutant protein. We have some clues and are testing them now.

LouLou: Dr. M. Do many of the researchers check on the KDA site for information. Our data base has grown considerably over the past 5 years. Thanks to Terry and Susaanne and the Board.

kelly: good question,, lou lou.

Dr__M_: I am an associate professor in Biochemistry at Thomas Jefferson University. I did some of my training with Dr. Fischbeck 10 years ago, but n now I have my own lab with 10 people or so.

Terryw: I am suprised to see new KD individuals from far away countries that have found us.

kelly: oooo ok so you are working on kennedys disease then etc...

Dr__M_: Yes, I do check the KDA website fairly regularly. I do it more from the personal side than the scientific side, since we regularly search new literature for scientific advances.

Coak: Kelly- Dr Merry is THE researcher at Thomas Jefferson University in Philadelphia

LouLou: Dr, M--So glad to have you on OUR TEAM. Thanks for being there for us.

kelly: ooo ok thank you, coak

Coak: She's "The Man" to use the vernacular.

UandS: Dr. Merry, is the idea that lowering the levels of DHT reduces the level of hormone binding thus keeping it out of the nucleus where it has a greater chance of being eliminated? Is this a stupid question?

LouLou: See Terry--all your hard work pays off.

Dr__M_: Yes, my entire lab works on KD. There are 4 Ph.D. students, 3 outstanding technicians, a post-doc (Heather Montie, who you might remember), and a professor on sabbatical (Ed Meyertholen, known to many of you). Erica, the student who worked to characterize the mice has received her Ph.D. and will move on to her post-doctoral training in a couple of months.

Terryw: Not only mine, it's a group effort. And that includes the KD members also sending in articles they come across. Thank you all

kelly: WOW-...!!!!! wish we had a team like that here in canada.

LouLou: Dr. M.---If you need any guinea pigs for research--Here we are.

Coak: It really is great to have so many experts working for/with us to help find a cure.

kelly: Iam available dr .m lol

murf: Kelly ... you do ..they just live down here LOL

kelly: lol well if they want to fly me to america that's fine lol

Terryw: I have put the KD in my Will to be able to continue to run & fund grants.

Dr__M_: No the question about dutasteride is not a stupid question at all. We know that dihydrotestosterone (DHT) binds to the androgen receptor (AR) better than testosterone (T) does, and we know that motor neurons are especially efficient at making lots of DHT. There are also other ways that the cell has to get rid of T. So we think that by blocking the conversion of T to DHT, we might allow the motor neurons to convert T to something that doesn't bind the AR as well (like estrogen, for example). This way, the AR will stay int he cytoplasm, not go to the nucleus, and get degraded better.

murf: Me too Terry

Terryw: TY murf

Coak: Terry-I think Murf wanted to also be named in your will -

Terryw: LOL

murf: That too!!

Dr__M_: Thanks for "The Man" reference, John!

murf: Good move John!

Terryw: Dr. Merry, Can non US citizens participate in USA based clinical trials

Dr__M_: It is really great to know that when we want to move something to a clinical trial, we will be able to work with Dr. Fischbeck and with all of you!

Coak: Dr. Merry -- some of us are geographically close. You can always call for a volunteer.

murf: Dr. Merry You are quite the LADY!!

Coak: 10-4 Murf. Let's buy her another dinner soon.

murf: And some of us can fly over any time

kelly: so I assume DR-M,, they will find a way to rejuvanate the dead cells concerning motor nerons ???? maybe? in the future

Dr__M_: Thanks, John, for that offer. It's very helpful to the lab, now that Ed Meyertholen, a KD patient himself, has joined for a year. He offered himself for a partial clinical exam yesterday at lab meeting, and it was very helpful. Regarding non-US citizens in US-based trials, my guess is that it doesn't matter, but you should ask Dr. Fischbeck to be sure.

Terryw: I wish my General doctor had the dedication & sincerity that Dr. Merry has towards KD.

Coak: All: FYI - Ed M. has run in the Boston Marathon for the last ___ years (5?). He has more strength than the rest of us combined.

murf: Alison said we could pass on her phone number at NIH to any one so please contact me by e-mail if you would like it.

Terryw: I think he has Bionics LOL

Dr__M_: Regarding rejuvenating dead cells, that's a difficult task. Stem cells are the only way to restore cells that are no longer there. However, the mice have given us some new information that is very hopeful. THe symptoms in the mice actually arise int he absence of cell loss. So we thing the neurons are dysfunctional for a long time before they die. If we can stop the disease progression before there are a lot fo neurons lost, we could really make a difference. We'll have to see if the same holds true (from EMG studies) in KD patients.

LouLou: I can't believe how well informed most of the KD'ers are about our disease.

Terryw: I am hoping that it is the web site & the KD conferences that have made that possible LouLou

LouLou: Thanks to the Drs. and researchers sharing their knowledge and experience with us.

UandS: Dr. Merry, do you know of any reason why heart meds might be difficult for Kennedy's patients?

Dr__M_: It's true that the KD conferences, and these chats, have really helped in disseminating information about research and trials.

Dr__M_: REgarding heart meds affecting KD, I don't know the reason for that.

murf: Ron ...I need to talk to you about the cruise at the BOD meeting

MikeG: Does anyone know what Ed's CAG repeat count is?

Dr__M_: It's really true that the conferences have been tremendously helpful. When Dr. Fischbeck and I used to be the only ones talking to KD'ers at the FSMA meetings, there was a different level of knowledge. You are all becoming experts.

wolfman entered the room.

LouLou: EX Spurts--has been little drips under pressure---LOL

murf: Morning Wolfman, we have Dr. Diane Merry on the Chat

Dr__M_: Knowing a specific CAG repeat doesn't actually give a lot of information about disease onset and progression, since is some much variability in age of onset and progression for a specific repeat length. It seems that there are many more factors affecting disease than simply the repeat length.

murf: Or has been spurts LOL

wolfman: morning to you all.

Coak: Mike - I know that Ed has family members with KD and that he got DNA tested early. He has not "deteriorated" as bad as some of us at this time.

Dr__M_: Sorry for my poor typing. I'm trying to type TOO fast!

murf: I really did in my legs on that last trip to NIH

Michael17860: Dr. Merry do you think that diet has anything to do with the progression?

kelly: Yeah There seem's to be some kd'er's who never ever had the muscle spasm's unlike me? why is that?

MikeG: I know - I'm doing good to walk a block... no way I could ever dream of running - even a few feet!

murf: We don't look at typing os spelling here....thank GOD

Coak: Run?? LOL

mobiusloop entered the room.

Coak: Andd wie ahl spel evriethng finne.

LouLou: It is amazing how some times major changes to my KD show up and other times very little change. Don't know why but hope for very little change.

murf: I'm with you John!

Dr__M_: Yes, there is so much variation from person to person in disease progression. The research community is really hoping that one thing that comes out of the clinical trial that Dr. Fischbeck's group is planning is a "natural history" of disease, with good objective markers that could be used for evaluating treatments.

LouLou: Don't worry about you typing--we can't read so well anyway.

mobiusloop: Sorry I'm so late, insomnia is messing up my sleep pattern

Terryw: If any of you have missed part of this chat you will be able to see the transcript online in the next couple of days. I have a few updates to post.

MikeG: Kelly - I too had the spasms in my 40's but they went away in my 50's. No more muscles to spasm I guess... LOL

kelly: DR. MERRY-? is kd kinda like ALS in gentic's???? or not?

Dr__M_: We also think that we may be seeing a variation in the rate of disease progression in the mice, and we are now determining ways to sort this out. Working with Dr. Marc Diamond on some of this.

Coak: Mike-LOL, same here.

murf: Terry did you get the one I sent last?

Terryw: It was a partial only

kelly: oh ok mike-g maybe when i hit 50 ILL be ok then lol?? hopefully then probably start falling down///10

murf: Mike me too and I'm not 50 yet...werd.

Dr__M_: Kelly, KD is not like ALS in the genetics of the disease. First, KD is always inherited, while ALS is inherited only in a small fraction of patients. There are many genes that cause ALS, while only one that causes KD. But there are similarities in that it appears that there is bad protein accumulation in ALS too, so there might be some common therapies.

Coak: All: I must go now. Thanks to Dr. Diane Merry for being here this AM. Bye for now.

Terryw: Murray are you talking about the 3rd Sept chat

murf: I cam in late remember

Coak has left the room.

Terryw: Yes then all I got was a partial

kelly: oh ok thank you DR. MERRY

UandS: Dr. Merry, do you know of any trend of heart problems associated with KD?

Coak entered the room.

Coak has left the room.

LouLou: so long John. Stay healthy.

Terryw: UandS I have not heard of any

MikeG: Dr - Speaking of FSMA... are you familiar with the Valporic Acid and Carnitine trial that they are starting?

murf: Yes

mobiusloop: Dr. Merry, my delimma is with my back. I have weakness in my left leg, probably because of disc degeneration. Left foot is dropped and has no strength while right foot is fine. Can we rule out KD and go on to operate on the spine?

Dr__M_: I don't know of heart problems trending with ALS, and I am not aware of any study that has addressed that issue. There of course may be some relationship to lower aerobic activity, in terms of keeping the heart muscle strong. There are so many factors that affect heart disease.

Terryw: mobious, Dr. Merry is more on the research side of the house not the clinical side.

Terryw: Maybe Dr. Fischbech would know better on that

UandS: Thanks, Terry and Dr. M. I had not read or heard of any either.

Dr__M_: Sorry, mobius, Terry is correct. I am not a physician. I would think that your neurologist and orthopedist should speak about this issue.

mobiusloop: OK I will have Dr. Chapman of the WSU Center try to contact Dr. Fischbech.

mobiusloop: Thanks

kelly: so DR. merry. is or?, the mouse model ever going to be successful? in terms of motor nerons

Dr__M_: I think that sounds like a good idea. Good luck with that decision.

Terryw: I would like to thank Dr. Merry and the past doctors/researchers that give their time to join our chats and answer questions. It is a big help and a moral boost to us all to see the dedication and care for us KDers.

Dr__M_: Kelly, I'm sorry, I didn't understand your quesiton.

kelly: the mouse model that your lab is working on is it successful

Chuck: Thanks Dr. Merry and I feel the chat was very informative.

Dr__M_: Thanks, Terry. I'm happy to join any time to give you updates and answer quesitons. I hope we have great news for you all soon!

UandS: Thank you Dr. Merry for all the information and for your time.

Chuck has left the room.

Dr__M_: Kelly, yes our mouse model is a good one, I believe, in that it develops disease like KD at an early age. This helps in testing drugs.

murf: Yes we all appreciate the time and effort you and all of your team puts in to try and find a cure/treatment. Thank You

Gary_KS: Dr. Merry, thanks lots............!!

Terryw: Any last questions for Dr. Merry?

MikeG: Thank you Dr Merry for all that you are doing for us.

Dr__M_: Your welcome, all. You had great questions!

kelly: thank DR> merry

Michael17860: Thank You DR. Merry.

Bob-B: Dr. M, thanks for all the work you and your lab are doing.

Terryw: Ok them Murray do you want to end the official chat?

mobiusloop: Thank you from me too!

LouLou: So long for now--Great chat--Thanks Dr. Merry.

murf: I'll save in a minute

Dr__M_: You are all so welcome. I will take your thoughts back to the lab to share with the scientists doing the bench-work.

END CHAT