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LK-Beitel
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Good morning
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Bruce
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Good morning, Lenore, where are you located this chilly morning?
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LK-Beitel
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Bruce, I am in Montreal, Quebec, Canada
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Bruce
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A beautiful city that I have had the good fortune of visiting a few times in the past.
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Terryw
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I would like to thank Dr. Beitel for joining us today. She is here to answer any questions you may have on research that they are doing.
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Bruce
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Could we get a short introduction of the type of research that is going on in her lab?
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murf
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Dr. Beitel can you tell us what you and your lab has been doing lately?
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LK-Beitel
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Our lab been studying the androgen receptor for many years and so we were very excited in 1991 when Drs. La Spada and Fischbeck found the mutation that causes Kennedy's disease was in the androgen receptor gene. We study the polyglutamine-expanded receptor protein in cells in the lab.
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LK-Beitel
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Lately, we have been focusing on the theory that the mutant AR can affect proteasome function in neurons. Proteasome are like the recycling bin of a cell, and dispose of unused proteins.
Bruce:Lenore, has there been anything new coming out of your research on the AR? Anything that will help move forward with a treatment or cure?
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murf
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So I guess our recycle bins are full??
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LK-Beitel
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If the proteasomes aren't working well, then other neuronal cell functions could be compromised.
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billeric
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Any breakthroughs dr. Beitel?
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LK-Beitel
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Right now we are doing basic research, and are hoping that once we understand how proteasomes are affected that ways could be found to make the proteasomes work better.
Bruce:It is my understanding that the AR can't clean itself (discard) the used proteins and it becomes so clogged that the AR or muscle eventually dies. Is that correct (in a very simplistic explanation)?
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LK-Beitel
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AR=androgen receptor. Bruce, you're basically right. The neurons could become dysfunctional if they can't degrade proteins properly.
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Terryw
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Dr. Beitel , do you work with Mice Models or flies in your research?
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LK-Beitel
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We are only working with models cells, not mice or fruit flies. Our expertise is putting normal and mutant ARs into cells and determining what happens.
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Bruce
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If I may ask, Lenore, how is your research project funded? Government grants, MDA, other?
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LK-Beitel
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Our research at this point is funded by the Canadian government through the Canadian Institutes of Health Research (CIHR). In the past, we also had funding from the March of Dimes
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murf
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Dr. Beitel - Will you benefit from a tissue donation program?
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Bruce
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Thank you for that information. We are trying to learn more about how research is funded outside the US.
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Bruce
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From your research perspective, Lenore, how far along is KD research as related to finding a treatment or cure?
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LK-Beitel
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Yes, It's always in the back of our minds that any findings will have to be tested in tissues from KD patients. We collaborated with Dr. Diane Merry to check if a specific kind of protein cross-linking was present in her model mice.
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Bruce
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The KDA hopes to launch a tissue donation program in 2006. All tissue will be used for KD research.
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murf
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We need to look at funneling Canadian donations to your research. Any ideas?
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billeric
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Will we be contacted Bruce to donate tissue?
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JoeK
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Is there any stem cell research at this time for KD?
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LK-Beitel
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I've seen tremendous progress in the 15 years I've been involved in this field. Researchers around the world are working cellular models, fly model and mouse models of KD. Particularly, in the last two years a number of treatments have been shown to improve symptoms in KD mice. I don't know how long it will take for these results to be translated into clinical trial. However, the paper by Katsuno et al in 2002 showed that reducing testosterone levels could help mice and I understand that the NIH is setting up a clinical trial next year on a related concept.
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Bruce
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The KDA will make an official announcement of the new program hopefully in the next three months.
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Terryw
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I feel that with the progress the researchers have made that they are very close to a major breakthrough.
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Bruce
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Lenore, it is my understanding that we are experiencing some technical problems with the chat room this morning where people are being kicked out of the chat frequently or having to re-enter their comments before they are posted. Sorry
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Terryw
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We thank all the researchers for their hard work and collaboration and hard work.
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LK-Beitel
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Re Canadian funding. Perhaps a not-for-profit organization that gives grants could be set up in Canada, so Canadians could get a tax deduction.
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Bruce
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Lenore, I think it is wonderful that so many research organizations are collaborating to share information and results. This has to help the process.
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JoeK
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I took testosterone shots for several --- not sure if it was good or bad. Insurance would not pay for treatment several years
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billeric
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I wore a testosterone patch for a year. Sounds like a big mistake.
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LK-Beitel
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I am not a medical doctor, but as I understand it, testosterone shot/patch would not currently be recommended. The thought was that the AR was not functioning well, so testosterone would help. However, now we know that testosterone could also cause the mutant AR to become harmful to neurons.
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Terryw
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Dr Beitel, does the AR always show a mutation in KD?
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FL-DON
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hindsight is great and error proof. at the time, testosterone was considered a big help for us. could be many other dead ends before a cure is found.
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Bruce
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You are making the case for clinical trials before widespread distribution of potential treatments.
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murf
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We are having difficulty finding someone in Canada to set-up a non-profit as it is a lot of work. If Canadians want to donate funds for your research what would be the best way to get it to you? research
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LK-Beitel
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Yes, but it is one particular mutation (an increase in the number CAGs to about 40 or more) that causes KD. Other mutations in the can cause androgen insensitivity or are associated with prostate cancer. None of those mutations however cause neurons to die.
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Bruce
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Can you explain that last comment further about causing neurons to die? I am a little slow this morning.
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Terryw
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I have a brother that has all the physical signs of KD, but he has had the DNA test 2 times from different labs and no sign of the AR mutation and his CAG is only 27. Strange
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LK-Beitel
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Yes, I understand that clinical trials are usually considered necessary before a new drug is used for treatment.
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murf
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There might be something there Terry.
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LK-Beitel
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Funds: Perhaps donations could be sent through the Hospital where we have our research lab. They gratefully accept donations.
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murf
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OK! we need details please send them to us
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murf
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Lenore If you could send details to the KDA e-mail later we may be able to help you with funding here
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Bruce
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Murray, I asked Lenore for that information already. I'll bring it forward afterwards to the BOD.
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murf
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OK great!!
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LK-Beitel
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Bruce, I used the term "neurons to die" rather than neurodegeneration. In autopsies of men with KD the number of certain types of neurons found in particular areas of the spinal cord (spinal anterior horn neurons) is reduced. In other words, neurodegeneration is not seen with other kinds of mutations in AR. Expanded CAG tract in the AR causes the polyglutamine-expanded AR protein to gain a new function harmful to cells.
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Bruce
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Thank you. That helps. So, the $64,000 question (for those of us old enough to remember that program) is: "What is your educated guess as to when to expect that a treatment will be discovered?
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murf
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We promise not to hold you to it!
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LK-Beitel
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Back to Terry. Was it only his blood DNA that was tested? In certain other AR mutations, it actually has been shown that cells can mutate back to have normal ARs again. It's possible that the blood cells that were tested reverted to a normal sequence, but the CAG mutation causing KD may be found in other tissues.
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Terryw
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yes just the blood test.
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Bruce
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So, what other tests would a person have to determine if they have KD (if the DNA test shows normal but all indications and family history show they could have it)?
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LK-Beitel
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My best guess it that treatment(s) for KD will be in place in 5-10 years. Many researchers are approaching the problem from many different angles so a combination of treatments may turn out to be useful.
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LouLou
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Dr. Beitel--it is dedicated researchers who will some day come up with the cure for KD. THANKS for caring.
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Bruce
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It has been said before, but you are our hope for the future. Your efforts are much appreciated.
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Terryw
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Dr. Beitel, Thank you again for joining our chat on your time off. This means a lot to us. Also thanks once again for your research into finding a cure/treatment for KD.
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LK-Beitel
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I understand there are clinical tests that can be done by neurologists. I've read about them but you could look it up in PubMed by searching for SBMA or "androgen receptor muscular atrophy" or "Kennedy's Disease".
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JoeK
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My older brother had problem with KD symptom, I have KD I have a niece that has it (rare) and a cousin and a 2nd cousin with KD. Thank Dr.
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LK-Beitel
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The chat has gone quickly. But it's been my pleasure and I look forward to meeting with you guys again the next time you have a conference.
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Bruce
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Lenore, again, we apologize for the technical problems we were having. It makes chatting more difficult. We hope to see you in Atlanta in October of 2006.
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murf
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Next conference will be in Atlanta GA Oct 11-13 2006
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