Kennedy's Disease Association

Kennedy’s Disease Knows No Boundaries...

Kennedy's Disease Chat Transcript  01-21-2006

Topic: Special Guest - Nicholas Di Prospero, M.D., Ph.D.

Host: Bruce Gaughran

Chat Participants:

BEGIN CHAT

You are in Kennedy's Disease Chat.

.

Bruce: BEGIN CHAT

Bruce: The KDA would like to welcome Dr. Di Prospero to our chat room this morning.  Today's topic is the: "NIH Drug Development Programs and the upcoming Kennedy's Disease Trial"  For those of you who missed it, here is a brief bio of Dr. Di Prospero.  He received his MD from the University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School and his PhD in pharmacology jointly from UMDNJ and Rutgers University.  Following training in internal medicine at Georgetown University, he received a fellowship in clinical pharmacology from NIGMS and joined the Neurogenetics Branch with Dr. Fischbeck at NIH in 2003.  He currently investigates mechanisms underlying polyglutamine pathogenesis and conducts a variety of clinical trials for neurodegenerative d

murf: Morning Nick

LouLou: Hi doc--thanks for joining us.

Dr_D: Happy to be here in cyberspace.

Bruce: The world has changed us all

billeric has left the room.

murf: How are our flies? LOL

billeric entered the room.

Bruce: Dr., can you give us an update on current KD research?

billeric has left the room.

Dr_D: In our lab (Fischbeck), there are people looking at different pathways involved in cell death and thereby ways to interrupt the process.

Bruce: Are you using fruit flies or mice?

Dr_D: Additionally,  Dr. Chen and I are starting the clinical trial using Dutasteride.  We should begin end of March/April.

Dr_D: We are using a cell line.

Dr_D: I do collaborative work with Dr. Taylor using the flies

MikeG entered the room.

Bruce: We know Dr. Taylor well here at the KDA.

Bruce: What is Dutasteride normally used for?

denny entered the room.

Dr_D: Dr. Taylor has made a very interesting observation using his flies and ones I have generated as well which we believe may point us to an effective therapy but I will let him chat about this.

Bruce: Dr. Taylor will join us in June as our guest.

Dr_D: Dutasteride is marketed for benign prostatic hypertrophy.

Terryw: So it's already and FDA approved drug?

murf: If their is anything we can help you with related to the clinical trial please just let us know.

Dr_D: It is a very safe drug taken once a day

LouLou: What is prostatic hypertropy?

Dr_D: prostatic hypertrophy is enlargement of the prostate gland which results in urinary difficulty.

Bruce: Is there some part of the drug that makes it look advantageous for a treatment for KD?

Terryw: How many KD individuals do you have signed up for the clinical trials, and how long will it last?

Terryw: many

Dr_D: We hope the KDA will spread the word for the trial and help us get volunteers for the study; the faster we recruit patients the faster we can complete the study.

Bruce: Dr, we are going to discuss how we can help in today's Board meeting.

Dr_D: We will need 50 volunteers and it will run for 2 years for each patient.

Terryw: do clinical trials cover travel expenses?

Bruce: We believe we can get the word our to several hundred possible candidates.

Dr_D: We cover travel, lodging, and $20/day for food.

LouLou: We have been involved with Dr. Chen since she first said she was going to have a clinical trial. How can we help?

Terryw: thanks for that info

Bruce: From all of us at the KDA, we will do everything possible to support your work.

Terryw: I know that some Canadian KD individuals were interested. Does it cover those in Canada

Dr_D: Yes.  Canadians are welcome

LouLou: Is there a cap on travel expenses?

Dr_D: No cap.

craig_h entered the room.

Terryw: how many time a year would travel be for the trial?

Bruce: For those that joined us late:  The KDA would like to welcome Dr. Di Prospero to our chat room this morning.  Today's topic is the: "NIH Drug Development Programs and the upcoming Kennedy's Disease Trial"  For those of you who missed it, here is a brief bio of Dr. Di Prospero.  He received his MD from the University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School and his PhD in pharmacology jointly from UMDNJ and Rutgers University.  Following training in internal medicine at Georgetown University, he received a fellowship in clinical pharmacology from NIGMS and joined the Neurogenetics Branch with Dr. Fischbeck at NIH in 2003.  He currently investigates mechanisms underlying polyglutamine pathogenesis and conducts a variety of clinical

Dr_D: We would see each patient every 6 months.

murf: I just talked to John and he said he would shot us an e-mail before the BOD meeting on the conversation he had with NIH. Nick were you in on that conversation?

LouLou: Alot of KD'ers will be glad to hear that. Many are not well off enough to spend alot out of pocket to join the trial.

craig_h: I am sure I missed this be being late, but is the trial scheduled to begin yet?

Terryw: The trial is in MD correct?

Bruce: Approx. April of this year.

gofr entered the room.

murf: MD?

billeric entered the room.

Dr_D: Dutaseride looks promising because it blocks the formation of the more potent more of testosterone called DHT.  This enzyme is found in motor neurons but not muscle.  We believe it will protect the neurons while sparing the muscle.  Dr. Taylor and I have good evidence in flies that this will be effective.

Terryw: state

Bruce: If you missed the beginning, you will be able to read the transcripts later this week.

murf: I can't believe I said that//10

Dr_D: No, murf, I wasn't in that conversation.

craig_h: when would patients know if they are a part of the trial? Dr. Taylor gave you my name Dr_D

murf: ok Say Hi to Dr. Chen for me

gofr: Thanks Bruce, and good morning all

Bruce: After the BOD meeting today, we hope to put out an email to all registered associates explaining the trial and asking if they are interested.

murf: I'll get John to copy you on the e-mail

craig_h: awesome

Dr_D: As soon as we have NIH approval (probably early March), we will contact everyone in our database and ask the KDA to advertise it.

craig_h: I'm only about 5 hours from Bethesda

LouLou: How soon will they make a list of who they would like to have in the trial? It would be nice to find out if we are included or not.

Dr_D: If people are interested in having their name in our database, please call Alison La Pean at 301-496-8969.

Terryw: me to, on a plane

Bruce: Dr, this trial sounds promising.  Besides trials in Japan that we know about, are there any other trials for KD right now?

Dr_D: The one in Japan and the one we are panning is the only ones I know of.

murf: I heard the one in Japan did not bring the results they wanted

Bruce: Are there any side effects from the drug?

Terryw: Bruce we think alike

Terryw: I will look it up on the net

Bruce: Dr, do you see patients with KD as part of a clinic or something like that?

mobiusloop entered the room.

LouLou: Anna Lee--How are you and Charlie doing? Louise--How are you?

Dr_D: We think that the problem with Lupron (the Japan trial) is that it shuts down all testosterone whereas we only want o shut it down in the neurons.

mobiusloop: Hello, this is too early for me

Dr_D: So, the men in the Japanese trial would lose the benefits of testosterone on their muscles which we would like to preserve.

LouLou: Hey--better too early than TOO LATE. LOL

Chuck4524: Ron,  we are doing ok.  Hi to you and your family.

craig_h: Dr_D , if this drug is a benefit, do you see a decrease in muscle loss, a stoppage in loss, or (please) a strength increase?

Bruce: Dr, let's say the trial is conclusively positive, does that mean that because the drug is already FDA approved it will become available as a treatment immediately?

Dr_D: The major side effects of the drug are decreased libido and impotence.

Dr_D: We would expect an increase in muscle strength (fingers crossed).

Bruce: Would that be great or what!

Dr_D: If the trial is conclusive, it would be available immediately.

craig_h: fingers crossed doubled here

billeric: pretty good trade off-in my book

Terryw: would Viagra counter effect the side effects

LouLou: Decreased libido--So what's new!!!

Terryw: counter

Dr_D: Please note that side effects are not seen in all patients; maybe around 1 in 10.

craig_h: impotence versus not the strength anyhow , no brainer trade off

Bruce: Dr, you being a scientist and a realist, what are the chances that this is going to work?  10% - 25% - 50%???

mobiusloop: I know that this my be a dumb question but has steroids or growth hormones been tried?

Dr_D: I think the chances are around 50%.

Terryw: that's as good as getting KD

LouLou: Sounds good to me.

Terryw: and I got it

Bruce: I believe I can state that everyone with KD is most appreciative of your team's work and also state that you are our hope for us and our families.

Dr_D: There are several types of steroids.  The one you may be thinking of are anabolic steroids (like athletes) which is really just testosterone.

billeric: well said Bruce

LouLou: How can we help with the everyday struggles in your lab?

gofr: So steroids being testosterone, and the Japanese test kills testosterone - a dead heat?

Dr_D: Testosterone has been tried in one early trail (Dr. Jerry Mendel in Ohio) which seemed to offer some benefit in the short term which is why we believe we need to preserve testosterone for muscles and shut it off around the neurons.

murf: I just got of the phone with John and we (KDA) will put out an e-mail to all associates in the next week explaining the upcoming clinical trial and asking for your assistance.

craig_h: I agree Bruce, just knowing there might be some help has raised my spirits

Dr_D: Sounds good, Murf.

wolfman has left the room.

LouLou: We want to let the Drs. and researchers that we are here and will do anything to help find a cure.

Dr_D: The only struggle in the lab is finding more time; anyone want to support my experiments to clone myself - LOL

mobiusloop: At 79 years a short term effect would be fine with me!

Terryw: Send me a fly, mouse and Petrie dish. I will do my part

Bruce: Good point!

murf: If you find that cloning machine please let me know LOL

Gary_KS has left the room.

Bruce: Dr, I am certain that there has to be a degree of excitement and optimism in the lab right now with the upcoming trial.

Chuck has left the room.

LouLou: Good to keep your sense of humor.

murf: Have to Ron

Dr_D: We are excited and we are happy to have such support from everyone in the KDA.

murf: Can't type!

gofr: The trial, then, involves drugs?

Gary_KS entered the room.

Gary_KS: I came back.

Chuck4524 has left the room.

murf: and we're happy you are looking for a cure!!!

Bruce: Yes, there is a drug mentioned earlier and it will be available on the transcripts later this week.

Bruce: The drug is already FDA approved.

Terryw: I will have this transcript posted by Monday

Chuck entered the room.

craig_h: Dr_D, will the trial be a blind/placebo group, or varying dosages?

murf: Craig the e-mail will explain all of this

craig_h: ok

gofr: Do you find sometimes that the side effects are worse than the disease?

craig_h: I'll try to be a patient patient   :)

Dr_D: It is a drug trial.  But please realize that it will be a placebo-controlled blinded study.  That means that half the patients (25) will be taking "sugar" pills and the other half will be taking actual drug (only one dose).  Blinded means neither the patient nor the researchers will know who is taking what until the end of the study; this is done to prevent bias.

murf: What are you talking about my third eye?

Dr_D: The think the side effects in the general population are mild, but since some of the KD folks have some of these problems already, I am uncertain how "bad" they may be.

Bruce: That is what the trial will also uncover.

Dr_D: Yes.

murf: Exactly

mobiusloop: Gotta go, breakfast is ready. I'll be watching for the transcript

Bruce: Take care

mobiusloop has left the room.

Dr_D: Additionally, the placebo group will also provide us with EXTREMELY valuable information about what we call natural history.

Bruce: Dr, besides the trial, is there other news/research taking place that the group might be interested in learning more about?

LouLou: So long *!@#--Watch for the trial.

Bruce: Natural history ... meaning what?

Dr_D: Natural history is how the disease affects each patient and therefore how to design better/faster trials in the future.

denny has left the room.

LouLou: So long *!@#-- Watch for the trials.

murf: You ok Ron?

LouLou: &*!@

gofr: What is involved in proving for sure that a person HAS kd?

LouLou: When using his name only the #@%%&&^^ comes up.

Bruce: In the research leading up to the trial, has there been a significant strength improvement in your lab tests?

denny entered the room.

Dr_D: Basically, we need to know at what rate muscle function (let's say) changes over a given period of time.  It allows us to determine how much a drug needs to do and how quickly to have an effect.

Dr_D: To make sure a patient has KD, we use genetic confirmation from a blood sample.

Bruce: Gofr, go to our web site and you will see information on testing for KD.  It is an easy and very effective way to conclusively determine if you have it.  (Blood test)

craig_h: so, during the trails, you will be measuring muscle strength how?

gofr: Thanks kindly - will do.

LouLou: I am sure that the progression of the disease which is different in all KD'ers will get different results in the trial.

murf: gofr - the process is explained on the website if you want to read up on  it

murf: Timing is everything //11

gofr: I DO want to, Murf and Bruce, and will do so right after the chat.

Dr_D: That's true, LouLou.  But by having a mix in both arms of the trial we hope to get a slope of the line through the data points

billeric: Dr.D.  will study participants have to travel to NIH?

Dr_D: Yes

Dr_D: We will cover travel expenses.

gofr: Where is NIH?

murf: Bethesda MD

LouLou: I'm sure the Drs. and researchers will want to keep track of each individual at least at the 6 months intervals.

Dr_D: We will measure muscle strength grossly using a functional assessment (asking you do do certain tasks like holding your head up) and then quantitatively by having you pull/push against a machine that has a transducer hooked up to a computer to read the amount of force generated.

LouLou: We have been looking forward to the trials since early Aug. of 2005.

Bruce: Dr, will part of the testing process require something other than taking the drug ... some exercise program for example or a different diet?

gofr: Ahhh,so, the 'head up' thing - that is the first that I have seen that mentioned!

Dr_D: No, Bruce, but those are important questions.

LouLou: Good question Bruce.

craig_h: that sounds great. I've wondered how my doctors at UVa hospital can check strength by push/pull against them, when I see then once a month

wolfman entered the room.

Bruce: I know some of us exercise every day and others don't.

Dr_D: I want to investigate exercise in the KD mice.

craig_h: oops, see them once a year

Bruce: Those of us who exercise, swear by it, but we might be doing more damage than good.

Dr_D: We have to accept a certain amount of variability with things like exerceise.

billeric: I think all of us would like guidance on excercise.  What kind and how much.

gofr: Do those who exercise find that there is an improvement in strength?

Dr_D: I agree with you; I believe mild exercise is beneficial and this is supported by studies in other populations of patients.

Bruce: I am an advocate of exercise (the right kind and not too much or too often).  It is a balancing act.

craig_h: I want to get back into the water exercise

Dr_D: The exact exercise program should probably be devloped with a physical therapist.

Bruce: My brother has KD and is in his mid 70's.  He still exercises every day.

LouLou: Some of the guys who exercise reguarly, also fall regularly. Can exercise of too much at a time cause more damage than good?

Dr_D: Yes.  As Bruce said it is a balacning act which is why I would advocate it being developed with a physical therapist.

craig_h: terry, I sent an e-mail asking if the KDA site was down. I finally got in on work computer. So ignore that email

gofr: Now to find a physical therapist that knows which way is up!

Bruce: We have about seven minutes left in today's chat.

Bruce: Gofr, you will find that you need to educate most therapists.

craig_h: Dr_D, thank you so much for working on KD, it raises my spirits to know that relief could be around the corner

billeric: It's been a good one Bruce.  I think we all feel a little more positive because of this chat.

Dr_D: It is a partnership and I am happy to be on the team.

Bruce: Most MDA clinics in the country have theraposts that are more educated in this area.

Dr_D: That's right Bruce.

craig_h: well, personally I would rather NOT be on the team, but it wasn't my choice !!!

murf: and we are happy to have you!

gofr: Sorry, MDA?

LouLou: Doc, thanks for coming on board to the chat today. You don;t know how much this chat means to us. THANKS!!

Dr_D: You are welcome!

billeric: Well said LouLou.

Bruce: Five minutes left in the chat.  What other questions do you have for our guest?

craig_h: the clinic in Bethesda, is there a long walk ?

Bruce: All of us live for the day that there is a treatment or cure.  If not for us, then for our families.

murf: taxis

MikeG: Dr are you familiar with the amino acit Arginine?

gofr: For sure, it helps a lot to know that there are efforts put forth to help overcome.

craig_h: well, I meant from parking lot

MikeG: acid

Dr_D: Valet parking!

Bruce: Again, I want to mention that the KDA will put out an email this week that will explain the trial and give everyone interested a chance to reflect their interest.

craig_h: ok , from Valet parking to office, lol

murf: The parking lot is down hill so its an up hill climb from the parking lot

Dr_D: We do have people walk as part of the testing, but it is limited.

wolfman has left the room.

Dr_D: Yes, I am familiar with Arginine.

murf: Most Hotels in the area will have a shuttle service

murf: We also have a list of hotels for you

MikeG: Do you see any benefit of a person with KD taking it?

Bruce: Dr., thank you so much for participating today.  We also want you to thank your entire team.  We really appreciate all of your efforts.

gofr: Arginine was mentioned before. Another trial drug?

craig_h: looking forward to the email, and possibly meeting some of you, especially Dr_D !!!

MikeG: ok

Terryw: Yes thank you

murf: Thanks Doc. we really appreciate what you are doing.

denny has left the room.

LouLou: Doc, Will the KD'ers have to pay for trvel then be reimbersed or will there be a voucher?

craig_h: and thanks to KDA for setting this up

MikeG: Thank you very much Doc.

MikeG has left the room.

Dr_D: Arginine is a simple amino acid found in protein.  There is some data to support that taking supplements in atheletes helps with reducing muscle fatigue, but I have not heard of any patint with KD taking it.

Gary_KS: Dr._D, thank you very much!

Bruce: END CHAT - if you want to stay on line and chat the chat room remains open 24 hours a day.