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September 29, 2005
Dr. Martha Nance Chat
The Washington Post has posted a fascinating transcript of an online chat with Dr. Martha Nance, a Minneapolis Huntington's Disease researcher. You can read the whole chat here.
A sampling from the chat:
On "Hot Flashes": Many people with HD seem to be metabolically "overactive", so that they are hot when other people are cool or comfortable....On Juvenile HD research: You are correct that the main focus of clinical research in HD is on the adults who make up about 90% of affected individuals. However, one could argue that the mouse models of HD used in laboratories are actually models of juvenile HD, as the HD gene mutations put into their cells more closely resemble those of children with HD than adults...
On what vitamins to take: Regarding vitamins, none have any proven effects, but the things people talk about include Vitamin E (with the recent report suggesting that doses >400IU/day can be harmful), multivitamins, which would cover any nutritional deficiencies, perhaps the B-vitamins, which are important for the brain, fish oil or omega-fatty acids--in standard doses, and Coenzyme Q10. There is a lot of research interest in CoQ10, although again no proof that it slows the course of the disease, and the doses that are being considered for research trials are very high--over 1,000mg/day. The decision about how much of what vitamin to take has to be made by the individual, knowing that there is no proof they will help at all! And do let your doctor know what you are taking...
On gene therapy: A very exciting "gene therapy" approach under study today is the idea of "gene silencing" by means of "RNA interference"--a recently discovered cell mechanism that has the ability to stop a gene from being expressed. Delivering the interfering RNA to the brain cells at the right time is the trick--and proving that the interfering RNA only blocks the gene of interest and not any other gene...Stay tuned, it is an exciting possibility!...
If you are going to have any chronic disease, whether it is HD, diabetes, or Parkinson's, you will do better if you a) eat right, b) sleep well, c) exercise regularly (especially if you have a movement disorder), d) engage in activities that you enjoy or that make you feel good (which for some people includes participating in research), and e) have good spiritual health--acceptance without resignation...
Responding to a question from Gene Veritas of the At Risk For Huntington's Disease blog: You are correct that the answers to HD may in fact be, or may quickly lead to, much better answers for other more common diseases like PD, Alzheimer's, and ALS. Just as is the case for cancer, there are similarities (and probably some differences as well, but let us focus on the similarities for now) between different types of neurodegenerative diseases. So a drug that slows down nerve cell degeneration in HD may also slow down nerve cell degeneration in AD or PD too. There are likely also to be unique aspects to each disease, so there may be treatments that are special for one or another disease that would not work for the others.
In addition, if we want to start treatments very early in the course of the disease, perhaps even before the doctor can clearly diagnose the disease, then the best disease to study first is HD, as we have the ability to know in advance who will one day develop HD. We do not yet have that ability for PD or AD. But if a treatment slows HD in the very earliest stages, then maybe it would do so also in the other diseases....That is an exciting thought!...
A comment on giving birth to a child that might have HD: On the other hand, music in America would not be the same had Woody Guthrie and his son Arlo not existed, or if my many patients who are successful doctors, lawyers, teachers, mothers, artists, children, etc etc etc not existed. One could even argue that HD is part of what gave Woody Guthrie his creative genius.
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As they say...read it all.
Posted by Dave at 06:28 AM | Comments (0) | TrackBack
Miraxion Update
Amarin has released a few more details on Miraxion (formerly LAX-101).
They've posted a corporate presentation on their website that includes these tidbits:
They've started enrolling people in their Phase III trial for treating Huntington's Disease. The enrollment is expected to end 2Q '06. The last person is expected to finish the trial in 4Q '06 and it looks like they'll be presenting the results to the FDA around 1Q '07. This would indicate that a FDA (hopefully) approval for use in HD would come by 3Q '07.
In this trial Miraxioni is being tested on HD patients with a CAG count less than 44 and with mild to moderate HD symptoms. Roughly two-thirds of all HD patients have CAG counts less than 44. They are measuring the results based on the patient's TMS-4 scores (Time course motor skills).
In the first Phase III trial, those on the placebo showed their scores increase (not a good thing) by 5.7%. However, those taking Miraxion showed a DECREASE in their scores (a very good thing) by 22.7% over the course of the 12 month study. As mentioned previously here, doses are 1 gram taken twice a day.
Amarin estimates there is a potential worldwide market for Miraxion of $500 million. A recent research report (which cannot be considered reliable) estimates that the Amarin could generate as much as $150 million in revenue per year from US sales (if approved).
Posted by Dave at 05:43 AM | Comments (0) | TrackBack
September 28, 2005
Bob Dylan
Some people consider their lives over when they learn they have the gene for Huntington's Disease.
That's a shame because many with the disease have accomplished so much. Last year I wrote about Bert Eymberts, the Redmond,WA firefighter who saved lives for over 20 years and ended up immortalized in a lifesize bronze honoring all firefighters.
Perhaps the best known person with Huntington's Disease was Woodie Guthrie, the folk singer. Aside from his musical legacy, his ex-wife ended up founding the organization that eventually became the largest HD organization in the United States. His son still raises money for HD.
However, it is his musical legacy that is still reverberating through popular music today as this article on Bob Dylan shows.
Dylan first came to New York on a quest to meet his idol Woody Guthrie, the iconic folksinger whose Huntington's disease landed him in a mental hospital. Dylan says no one reached him musically before Guthrie... Guthrie "had a particular sound, and besides that he said something," Dylan recalls. "He was a radical -- (I thought) that's what I want to say. I want to say that."
Bob Dylan is just one of many artists influenced by Guthrie. Dylan's work has influenced Joan Baez, Peter, Paul & Mary, The Rolling Stones, The Byrds, Neil Young, & John Lennon. From MTV:
Bob Dylan's influence on popular music is incalculable. As a songwriter, he pioneered several different schools of pop songwriting, from confessional singer/songwriter to winding, hallucinatory, stream-of-conscious narratives. As a vocalist, he broke down the notions that in order to perform, a singer had to have a conventionally good voice, thereby redefining the role of vocalist in popular music. As a musician, he sparked several genres of pop music, including electrified folk-rock and country-rock. And that just touches on the tip of his achievements. Dylan's force was evident during his height of popularity in the '60s -- the Beatles' shift toward introspective songwriting in the mid-'60s never would have happened without him -- but his influence echoed throughout several subsequent generations. Many of his songs became popular standards, and his best albums were undisputed classics of the rock & roll canon. Dylan's influence throughout folk music was equally powerful, and he marks a pivotal turning point in its 20th century evolution, signifying when the genre moved away from traditional songs and toward personal songwriting. Even when his sales declined in the '80s and '90s, Dylan's presence was calculable.
Martin Scorsese now has a PBS documentary on Bob Dylan called "No Direction Home". The reviews have been outstanding so check it out when you get a chance and think back to the man with HD who inspired him in the beginning.
Posted by Dave at 07:24 AM | Comments (0) | TrackBack
ReNeuron Update
ReNeuron reports that it is still on track with its ReN001 stroke treatment program. They plan to apply for Phase I clinical trials next year.
ReN001 is a stem cell therapy designed to repair brains after strokes. ReN001 uses the same cells as their ReN005 treatment their developing for Huntington's Disease.
Successful trials of ReN001 would be very encouraging for those following the developments of the ReN005 Huntington's treatment.
More background in this post from last year.
Posted by Dave at 07:07 AM | Comments (0) | TrackBack
Rape Trial
I didn't hear about this story until yesterday.
A trial is being held in Pittsfield, PA for a man charged in raping a 44-year-old Huntington's Disease patient in a nursing home. You can find the story about the case here (warning: graphic details).
Posted by Dave at 06:52 AM | Comments (0) | TrackBack
September 12, 2005
FDA Blesses HD Phase III Trial
The Miraxion/LAX-101 trial, TREND-HD, now has the FDA's green light. If you or a loved one has got mild- to moderate-HD then call 1-800-487-7671 to see about enrolling in this study. (More Info Here.)
Here's some key information from Amarin's press release:
The U.S. and European trials will be multi-centre, randomized, double blind, placebo –controlled studies of Miraxion at 43 sites in the U.S. and up to 28 sites in Europe. The trials are expected to involve a total of up to 540 Huntington’s disease patients with approximately 300 in the U.S. Phase III trial and approximately 240 in the European Phase III trial over a 6 month period. Patients in the U.S. trial will participate in a further 6-month extension period. ...The primary endpoint of the trials will be to determine whether Miraxion taken 2 grams per day (1gram twice daily) results in clinically and statistically significant changes in the Total Motor Score-4 subscale of the Unified Huntington’s Disease Rating Scale (UHDRS).
Here's the full press release:
Amarin Receives Special Protocol Assessment From FDA For Two Pivotal Phase III Clinical Trials For Miraxion In Huntingdon's Disease
LONDON, United Kingdom, 12th September, 2005 -- Amarin Corporation plc (NASDAQ: AMRN) today announced that it has reached an agreement with the U.S. Food and Drug Administration (FDA) under the Special Protocol Assessment (SPA) procedure for the design of two pivotal Phase III clinical trials of MiraxionTM (ultra-pure ethyl-EPA) in Huntington’s disease. The Special Protocol Assessment (SPA) is a process under which the FDA provides evaluation and guidance on clinical trial protocols for Phase III trials.
Rick Stewart, Chief Executive Officer of Amarin, commented; "Reaching agreement with the FDA on the trial designs is a positive development for Amarin. This is a major milestone for the company and we look forward to immediate enrollment in the U.S. trial."
The U.S. and European trials will be multi-centre, randomized, double blind, placebo –controlled studies of Miraxion at 43 sites in the U.S. and up to 28 sites in Europe. The trials are expected to involve a total of up to 540 Huntington’s disease patients with approximately 300 in the U.S. Phase III trial and approximately 240 in the European Phase III trial over a 6 month period. Patients in the U.S. trial will participate in a further 6-month extension period.
The Huntington Study Group (H.S.G.), based at the University of Rochester, will conduct the U.S. clinical trial on behalf of Amarin. The H.S.G. is a non-profit group of physicians and other health care providers from medical centers in the U.S., Canada, Europe and Australia, experienced in the care of Huntington’s disease patients and dedicated to clinical research of Huntington's disease. The European clinical trial will be conducted in collaboration with EURO-HD and ICON, a leading contract research organization (CRO). EURO-HD is a non-profit group of physicians and other healthcare professionals dedicated to the research and care of Huntington’s disease patients.
The primary endpoint of the trials will be to determine whether Miraxion taken 2 grams per day (1gram twice daily) results in clinically and statistically significant changes in the Total Motor Score-4 subscale of the Unified Huntington’s Disease Rating Scale (UHDRS).
Posted by Dave at 10:42 AM | Comments (0) | TrackBack
Bad Science (Writing)
...or why the media often gets in wrong in reporting science.
Several good points from this excellent article that should be read by all. An excerpt:
Science is done by scientists, who write it up. Then a press release is written by a non-scientist, who runs it by their non-scientist boss, who then sends it to journalists without a science education who try to convey difficult new ideas to an audience of either lay people, or more likely - since they'll be the ones interested in reading the stuff - people who know their way around a t-test a lot better than any of these intermediaries. Finally, it's edited by a whole team of people who don't understand it. You can be sure that at least one person in any given "science communication" chain is just juggling words about on a page, without having the first clue what they mean, pretending they've got a proper job, their pens all lined up neatly on the desk.
Posted by Dave at 08:40 AM | Comments (0) | TrackBack
September 11, 2005
Old Drug Shows New Promise
From the University of California - San Francisco:
Old drug shows new promise for Huntington's Disease
Clioquinol, an antibiotic that was banned for internal use in the United States in 1971 but is still used in topical applications, appears to block the genetic action of Huntington's disease in mice and in cell culture, according to a study reported by San Francisco VA Medical Center (SFVAMC) researchers.
The study, led by principal investigator Stephen M. Massa, MD, PhD, a neurologist at SFVAMC, was reported in the August 16, 2005 issue of Proceedings of the National Academy of Sciences.
Huntington's disease is a hereditary, degenerative, and ultimately fatal disease of the brain that causes changes in personality, progressive loss of memory and cognitive ability, and a characteristic uncontrolled jerking motion known as Huntington's chorea. There is no known cure or effective treatment. A person who carries the mutant Huntington's gene may pass it on unknowingly because the disease often manifests in early to late middle age after the carrier's children have already been born.
During the course of the disease, the Huntington's gene causes the production of a toxic protein, mutant huntingtin, in neurons (brain cells). Eventually the protein kills the neurons, causing the disease's degenerative effects.
In Massa's study, Clioquinol appeared to interrupt the production of mutant huntingtin. In the first part of his study, Massa and his research team tested the effect of Clioquinol on neurons in cell culture that contained a form of the mutant Huntington's gene. "We found that not only did cells look better and survive a bit longer when exposed to the drug, but they also seemed to make less of the toxic protein," observed Massa, who is also a clinical assistant professor of neurology at the University of California, San Francisco (UCSF).
Based on the in vitro results, Massa decided to test the drug in vivo, on mice bred to express the toxic huntingtin protein. The mice were given approximately 1 milligram of Clioquinol per day in water. After eight weeks of treatment, they had accumulated four times less toxic protein in their brains than control mice given water alone. The experimental animals lived 20 percent longer than the control animals, did better on tests of motor coordination, and had less weight loss.
"It's a limited study, in that we used the same drug dose on all the animals as opposed to comparing different doses, but fairly convincing," Massa concluded. "Together, the in vitro and in vivo results suggest that Clioquinol has an effect of decreasing the symptoms of Huntington's, its pathology, and perhaps even the actual production of the toxic protein."
However, he noted, "the drug's mechanism of action remains unclear." The clearer the mechanism of the drug, he explained, the better the chance that researchers might eventually be able to create a medication that is both safe and effective.
Like some other antibiotics, Clioquinol is known to be a chelator -- that is, it binds metals in body tissues, particularly copper and zinc, and removes them when it is excreted. Massa and other researchers believe that this chelation effect may interfere with production of the mutant huntingtin protein in some way. "But there are still a couple of explanations we need to rule out," he said.
To that end, Massa's next studies will involve the creation of an in vitro system in which toxic and non-toxic forms of huntingtin are made in the same cell. He and his team will then evaluate the effects of Clioquinol on several phases of protein synthesis within the cell. Massa hopes these experiments will confirm initial indications that Clioquinol preferentially interferes with synthesis of the toxic form of the protein. "Then we can move on to trying to isolate the actual mechanism of the drug," he predicted.
"However," Massa cautioned, "the record of successfully translating drugs from animal to human use is not good."
Clioquinol has shown promise as a potential treatment for Alzheimer's disease in recent studies in mice and humans. Apparently through chelation, it interferes with the creation of beta-amyloid plaque in the brain, which has been implicated in the progression of Alzheimer's symptoms.
Currently, Clioquinol is banned for internal use in many countries because of its side effects. In Japan in the late 1950s and 60s, the drug was found to cause a neurologic condition called subacute myelo-optico-neuropathy (SMON), with symptoms including visual loss, muscle weakness, and numbness, in several thousand people. However, noted Massa, the doses given in current clinical trials are much smaller than were commonly prescribed in Japan. In addition, he explained, it has been found that vitamin B12, when taken along with the drug, protects against its potential toxic effects.
Co-authors of the study were Trent Nguyen, PhD, and Aaron Hamby, BS, of SFVAMC and UCSF.
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The research was funded by a grant from the U.S Department of Veterans Affairs.
Posted by Dave at 02:44 PM | Comments (0) | TrackBack
September 06, 2005
Looking For HD Families - Katrina
HDSA is coordinating efforts to identify and locate HD families who have been displaced and/or affected by Hurricane Katrina, and help them receive appropriate medical care and support services. We request your help in this effort.Please notify us of any HD patients/families you know who have been displaced or are in need of help
If you have a local center where displaced persons are being processed, please find out how you can contact the people managing intake to make them aware that we can help with medical and social resources for HD patients and families.
Distribute our email, Katrina@hdsa.org and our number 1-800-345-HDSA (4372) extension 26 to patients, families and medical personnel to request help or provide information.
Please forward any other ideas you have on how we can identify our families and help bring them relief for Fred Taubman (212 242 1968 ext 29 ftaubman@hdsa.org), who is coordinating these efforts.
Thank you for your help. We hope that through these efforts we will help the HD patients and families affected by this tragedy.
Barbara Boyle
Posted by Dave at 06:37 PM | Comments (0) | TrackBack
Disability Benefits - How To
This is the best resource on the web for information on applying for disability benefits for those with Huntington's Disease - http://huntingtondisease.tripod.com/benefits/index.html
Posted by Dave at 10:34 AM | Comments (0) | TrackBack
September 05, 2005
Celebration of Hope Dinner
HDSA has had their annual Celebration of Hope dinner and it looks like it was a financial success. $54,000 was raised for the local HD Center of Excellence.
Posted by Dave at 07:40 AM | Comments (0) | TrackBack
September 04, 2005
Vitamin E
The vitamin acted as an antioxidant in the mice, slowing the ageing process,” Boveris explains. They found that the mice that had received vitamin E showed reduced levels of free radical mediated reactions and oxidative damage in their mitochondria, the cell’s power packs, than other mice.“Normally in ageing there is an increase in products of oxidation, but the mice on vitamin E actually showed a reduction. And the protective effects were particularly noticeable in the brain,” Boveris says. He admits that he has increased his personal intake of the vitamin to 400 mg per day.
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