In this issue:
On reflection, we have witnessed enormous advances in research, care and management of people affected by Huntington's Disease symptoms and their families. The isolation of the gene in 1993 and subsequent trials of drugs and treatments have provided great hope and expectation for us all, and the future looks brighter and brighter with each release of research information and knowledge.
The Association has changed considerably since that first meeting, where a small group of people formed the basis of the present organisation, and today our membership totals in excess of 470. There are however many more non-members who access the Association's services. Your financial membership and support is vital in maintaining both financial stability and morale within the Association and its staff.
I would like to encourage each of you, who are not financial members of the Association, to seriously consider your position, as payment of membership and donations form a large part of our annual fundraising and our ability to lobby government and make representations on behalf of our clients. Generally speaking, we provide a Newsletter to all persons listed on our confidential mailing list, however the costs of maintaining a service such as we provide, continue to rise, and any available assistance would be appreciated.
As your President, I look forward to a busy and productive year, and I anticipate meeting with many of you, especially at our 25th Anniversary Celebrations.
Gerry Doyle, President
My name is Tracey Hender and I am also gene-positive with Huntington's Disease. I am currently undertaking a Masters of Training and Development at Edith Cowan University (Western Australia).
As my Masters Project, I am putting together a support package for people who have been through the predictive testing procedure and received a gene-positive result. As such, I would be extremely grateful for your participation in a short questionnaire which hopes to identify those areas where people like ourselves would like information or support.
Questionnaires are available through the HD Office in Brisbane - please contact Gwen if you would like one forwarded to you. All information will remain confidential.
Happy New Year from Cathy and Gwen. We hope all of you found enjoyment during the festive season.
The New Year has begun at the HD Centre with some changes to the manner in which we offer some of our services. For many years we have attempted to provide a weekly Day Respite Service for in excess of 20 people experiencing Huntington's Disease symptoms. Some of these people live as far away as Redcliffe, Redland Bay and Ipswich. Providing transport for all of the clients has been our greatest challenge.
After a lot of consideration a decision has been made to restructure the entire Day Respite Program. In the past, the service was offered on a Tuesday and a Wednesday, with each client attending on one of those days.
As from the 6th February, 2001, we have decided to combine the two groups and offer the Respite Service on Tuesdays only. Inevitably, when services are being offered to persons affected by a degenerative condition, consideration as to the appropriate level of function of each client is constantly reviewed.
The Management Committee has made the decision to reduce the number of persons participating in the program to 15, thereby providing a more stimulating service to our clients who are functioning at a relatively high level. For those persons who will not be included, the Welfare staff will offer increased support in a variety of ways, some of which are yet to be determined.
Kathy Roberts and Theressa Byrne both resigned as Facilitators of the Day Respite Program at the end of last year. Kathy decided to take a well earned break after many years of involvement with our Association and Theressa gave birth to a second baby girl late last year and is unable to return to the work force at this time. I would like to express our thanks to Kathy and Theressa, and I trust they will visit with us whenever they are able.
Kaye Evans, who has been an excellent volunteer in the Day Centre, was appointed to replace Kathy; and Jasmine Wilson, who came to us as a student and maintained her interest, has been employed to replace Theressa. We welcome both Kaye and Jasmine and trust they will enjoy working with all of us. Each of these women has experience in the respite area.
Providing a respite service is a very costly, labour intensive exercise, and part of the decision process to restructure our operation involved looking at the overall costs, and maximizing the benefits for the clients participating in the weekly program.
The Association receives some Government funding for respite services; however, the majority of the costs are met through fundraising, donations and membership of the Association. We believe we can offer a fairer, cost-effective service to a wider cross section of our families.We will keep you informed in future Newsletters as to our success or otherwise.
Regional visits by both Welfare staff are being planned, with Cathy working in the Bundaberg area in March and Gwen working in the Mackay area in February and the Townsville and Cairns areas in March. If you have issues to address, please call the HD Office. We will be attempting to contact all of the families known to us in these areas.
On behalf of the Association, I would like to express my condolences to the families of Alan Morgan and Sherry Jukes who have recently passed away. Both Sherry and Alan were attending our Day Respite Centre, and will be sadly missed by us all.
Townsville Support Group - Another year upon us! I hope everyone is back to normal after the festive season. Just to recap on the Group's last six months of the year 2000:
Vic Wakefield, Chairperson
Bundaberg Support Group
We were thrilled with our latest fundraising efforts in the Sunrise Rotary Trailer Raffle. The Group raised $3,000.00. This result was due to a tremendous effort put in by Nancy who spent many hours of her time selling tickets. Nancy, thank you for your dedication, not only in fundraising, but also for your assistance to HD families in the area.
The Second Annual AstraZeneca Lecture presented at the Huntington Society's Annual General Meeting and Conference held October 19-21, 2000 in Montreal, Quebec. This year's guest lecturer was Dr. Gillian Bates, Professor of Neurogenetics at King's College, London, and one of the world's leading HD investigators.
The scientist who developed the first mouse model of Huntington disease, Dr. Bates was also the first to report breakthrough observations of protein balls in these animals. "The pace of HD research is phenomenal," said Dr. Bates, setting the stage for her presentation. She emphasized that in the space of four years, HD research has progressed from its first animal model of HD, to drugs that delay symptoms in the HD mouse.
Genes and Proteins: As Dr. Bates explained, the only difference between the normal version of the HD gene and the one which leads to the disease is the number of CAG repeats that the gene contains. Someone with 33 repeats will not have Huntington's, someone with 43, will. It is also the case, she said, that there is a rough correlation between the number of CAG repeats and the age at which Huntington disease begins.
Scientists are working hard to understand these problems: Why is it that a few extra CAG repeats trigger disease? What other factors help to explain the age of onset? Genes produce proteins, and Dr. Bates suggested that the protein produced by the defective HD gene probably folds into a different shape than the normal protein. This leads to the formation of protein aggregates in brain cells, and in some way which we do not yet fully understand, is linked to the signs and symptoms of Huntington's Disease.
Mouse models of HD: Dr. Bates herself developed the first transgenic mouse model of Huntington's Disease. She pointed out that this model, and others developed in the past few years, are essential for studying the early steps in the disease process, and for testing new strategies for treatment.
With the HD mouse, scientists have been able to gather all kinds of new insights into the disease process in Huntington's - the formation of protein balls, the early signs of cell dysfunction, the onset of symptoms, and actual brain cell death.
Scientists now know that certain genes are "turned up" or "turned down" in conjunction with HD. These other genes and pathways not previously associated with HD are providing invaluable clues as to how the progress of the disease might be slowed down or stopped.
Dr. Bates also took the time to discuss the development of a new mouse model by Dr. Ai Yamamoto (see Horizon, 98.2000). The so-called reversible model was developed with a "switch" that allows researchers to "turn off" the expression of the HD gene. The mouse develops symptoms of HD in the same way as the Bates mouse. However, when the HD gene is switched off, the symptoms of HD in the mouse start to reverse, and the protein aggregates begin to disappear - a remarkable finding, in Dr. Bates' view. This does not represent a treatment. But it does mean that if it is possible in the future to find a treatment which blocks the HD gene, there may be greater hope even for those with early symptoms.
Approaches to Therapy: According to Dr. Bates, given what is now known about HD and how it works at the cellular level, investigators are trying to find drugs that will:
To that end, large-scale drug screening has been undertaken to identify compounds that have an effect on the huntingtin protein.
To date, Dr. Bates indicated that tens of thousands of compounds have already been screened. Thus far, 689 compounds have been identified that affect the process of aggregation, 78 of these at relatively low concentration levels.
In addition to testing experimental compounds, investigators are also testing drugs which are already used for other conditions.
Riluzole and minocycline, for example, have both shown potential, and are being explored further as possible therapies (see Horizon, 98:2000).
Closer to the cure: In concluding her presentation, Dr. Bates asserted that "everything is in place" for finding a cure. To show just how fast the research is progressing, she listed the more critical breakthroughs in research that have occurred since the discovery of the gene.
The underlying optimism was unmistakable. As Dr. Bates put it, "Things are really accelerating." In other words, she and her colleagues in the research community are convinced that many new breakthroughs are just around the corner.
RM Reprinted from "Horizon", No. 99 Winter 2000,
A jellyfish from Puget Sound off the Washington state coast is helping scientists tackle one of the most daunting challenges facing drug-hunting researchers, quickly turning the spate of new gene discoveries into innovative medicines.
The jellyfish species, Aequorea victoria, emits a green fluorescent flash when it's agitated - likely an attempt to defend itself by confusing enemies.
Scientists at Aurora Biosciences Corp., a small biotech company in San Diego, are harnessing the chemical responsible for the sea animal's eerie green glow in experiments designed to literally illuminate new ways to attack a host of gene-related illnesses.
Aurora have announced that it will soon begin experiments using the gene that generates the jellyfish's green fluorescent protein, or GFP, to search for a long-elusive treatment for Huntington's Disease, an inherited disorder that erupts without warning at midlife, causing severe muscle gyrations, degeneration of brain function and, eventually, death.
Although the gene and its illness-causing defect responsible for Huntington's was identified seven years ago, following an intense 25 year gene-sleuthing effort, no headway has been made in finding a treatment.
Drug makers have been unwilling to stake the funds needed to find a cure because the gene defect is complicated and the number of people with the disease - about 35,000 to 50,000 Americans have it - is relatively small. "We've been terribly frustrated because we had found what causes the disease but we couldn't get any company to look for a drug to counter the defect's devastating effects," says Nancy Wexler, the co-founder, along with her 92-year old father, Milton, of the Hereditary Disease Foundation.
The foundation launched a quest for the Huntington's Disease gene in 1968 after Dr. Wexler's mother developed the illness that had also claimed her mother's three brothers. "One major problem we've faced is that, despite years of research, we still don't know the role the gene plays in the body and how, when defective, it causes disease," says Dr. Wexler, who has a doctorate in psychology and is a professor of neuropsychology at Columbia University.
Researchers hope that the jellyfish-produced green light will not only help show how a defective gene gives rise to disease, but will also provide a simple, visual way to determine which drugs can inactivate a gene's deadly effect.
Roger Tsien, a biochemist at the University of California, San Diego, has tinkered with the jellyfish's gene, making a new gene that produces a very bright version of the light. Aurora researchers, in turn, have created techniques that allow them to fuse the light-making portion of the proteins with portions of disease-causing genes, such as the one that causes Huntington's Disease.
In Aurora's coming experiments, researchers plan to test hundreds of thousands of chemical compounds to see if any of them can prevent or slow the death of cells caused by the bits of Huntington's gene.
In the technique developed by Aurora, any drug that inactivates the fused protein or modifies its activity would cause a change in the colour of the light emitted. In most instances, the colour changes from green to yellow or to a colour in between the two. "In the past there was no way to tell if a test compound was having any effect on the gene or the protein it makes," says Brain Pollok, senior director of discovery biology at Aurora.
The light-emitting gene may also help determine which parts of the defective gene are causing harm and need to be attacked by experimental drugs, Dr. Pollok says. "What we'll try to do is fuse GFP with many parts of the Huntington's gene, and we'll track which of the fused proteins make cells sick or die." If successful, the green-light technique could benefit other drug makers trying to exploit the flood of gene discoveries arising from the human genome project.
While scientists are linking thousands of previously unknown genes to illnesses both rare, such as Huntington's, and common, such as heart disease and arthritis, how these genes function in sickness or in health is largely unknown.
Indeed, in the past year or so a new discipline of science, called "functional genomics," has arisen as researchers in academia, giant pharmaceutical companies and start-up biotech firms race to figure out what newly discovered genes do and why, when defective, they cause disease. But, researchers at major drug makers acknowledge, if they have to wait until scientists elucidate the function of genes before they can initiate drug discovery projects, it could take decades before new gene-based medicines are found.
"What we've developed is an ability, using GFP, to test thousands of chemical compounds against (disease related) genes without having to know what the gene does in cells or why alterations to the gene results in disease," says Dr. Pollok, who has a doctorate in biochemistry.
In recent months, published scientific reports of Aurora's ability to track down drugs against disease-related genes before knowing function has led a number of major drug makers, such as Pfizer Inc., Bristol-Myers Squibb Co., and Merck & Co., to employ the company's drug-hunting techniques in deals worth tens of millions of dollars each.
Since the Huntington's Disease gene was found, researchers who have been supported in large part by Dr. Wexler's small foundation have found that the defect involves a very strange bit of evolution.
In people born with the defect, who are fated to develop the disease by the time they are 40 or 50 years old, the gene contains a tiny segment of DNA that is abnormally repeated over and over - an accordion-like expansion of genetic material that is also found in people with other neurodegenerative illnesses such as Alzheimer's or Parkinson's.
There is reason to believe that Huntington's Disease arises when mutant proteins made by the defective gene begin sticking together inside nerve cells, and that over time this accumulated mass of material simply gums up the machinery inside the cell. This gradual buildup may explain why the disease takes decades to arise.
"The ideal would be finding a drug that blocks this protein aggregation," says Ronald Wetzek, a protein chemist at the University of Tennessee at Knoxville.
The trick to finding such a drug is devising an experiment that can measure the impact of thousands of chemical compounds that might interfere with the gene's lethal action.
Dr. Pollok says once Aurora begins its experiments in the next few months, it expects within a few weeks to come up with about 5,000 compounds that have some impact on the Huntington's gene. The researchers then plan to ship these compounds off to academic scientists who will begin to test these compounds in other cell experiments.
The hope is that, perhaps within a few years, scientists may find drugs that can be taken for life by people who have inherited the gene but haven't yet developed the disease.
The new medicine, it is hoped, would work by simply blocking the gene's deadly action, though exactly what that action is may still not be known for many years, even after a drug is available.
Reprinted from "Huntington's Disease Association Newsletter" United Kingdom, Issue 58, Winter 2000.
The mapping of the human genome has been a great step forward, but privacy remains a key concern. The report that the mapping of the human genome has been completed at least three years ahead of schedule is a brilliant success story of technology, international co-operation and human determination.
A new medical encyclopaedia for all time is now in our hands. But big questions about the use of genomic data, and about ethics and law, lie ahead.
At the heart of the puzzle will be the need to avoid irrational and unfair differentiation between people on the basis of their genetic profiles.
Sometimes making distinctions between individuals can be justified. A person with a highly contagious disease may need to be isolated for the protection of society and the proper treatment of the individual. However it should be borne in mind that the history of the twentieth century was one of unrelenting irrational and unwarranted discrimination. Such discrimination is still going on.
The grounds for discrimination are frequently based in the genome: a person's race, skin colour, gender, disability, and sexual orientation. All of these are wholly or partly genetic in origin.The Universal Declaration of Human Rights in 1948 gave the world a beacon of hope to help steer humanity away from discrimination. While much progress has been made, much still remains to be done.
The human genome presents new risks of unreasonable differentiation on the basis of genetic testing. We must make sure that in the new century, the mistakes of the past are avoided.
Many genetic triggers for inherited cancers and other serious diseases have already been identified. Among those discovered are the genes that mark the presence of late onset disorders such as cystic fibrosis, muscular dystrophy, Huntington's Disease and the two genes apparently related to Alzheimer's Disease.Despite the accuracy of the genetic detection, there may be enormous variation in the age of onset and the range of symptoms that afflict individuals.
In the past, family members would know generally about the inherited conditions of succeeding generations. In the future, they will know exactly. The outcome of the Human Genome Project will ultimately ensure that all genetic causes of human differences can be identified.
The risks of genomic differentiation and prejudice are real. Unfortunately, despite progress in education and even in law, recent history teaches us that we should be concerned.
Millions of people in the twentieth century lost their lives, or suffered profoundly, because of genetic distinctions. Dangers of adverse discrimination in the future using genomic data may arise unless adequate protections are quickly put in place.
Insurance is a potentially important example. In the past the availability of insurance (and the rates of premiums) were ordinarily fixed by reference to the sharing of uncertain risks. Now it will be technically possible to subject people seeking insurance to genetic tests. Risks may no longer be shared if the progress of genetic disability becomes absolutely certain.
Employers may wish to utilise genetic testing. They may argue that training, disability benefits and the cost of sick leave justify having exact knowledge about the medical prognosis of their staff. Will individuals who "fail" the genetic test be refused employment?
How do we protect the privacy of such medical data, in an effective way, from the powerful who are inquisitive?
Some scientists believe that sexual orientation is, at least partly, genetically determined. If this were established, would it help or hinder the world-wide efforts to reduce discrimination against people on the grounds of sexuality? It might help by proving that sexuality is a natural variant in the human species, not a defiantly chosen "lifestyle" flouting society's moral rules. But out of fear or hatred, such a discovery might also hinder progress by leading to demands for destruction of foetuses evidencing such genes.
In November 1997 UNESCO adopted the Universal Declaration of Human Genome and Human Rights. This contains the principle that "no-one shall be subjected to discrimination based on genetic characteristics that is intended to infringe or has the effect of infringing human rights, fundamental freedoms and human dignity". But how will this large principle be assured without strong practices in the medical professions and effective legal protections for the privacy of genetic data?
In the future, will that privacy be confined to the individual concerned? Does an individual's genetic information belong to the entire family?
The mapping of the human genome is good news for humanity. Scientists will use their new knowledge to combat more than 5,000 major genetic conditions that afflict the human family.
It is our duty to share this information with people everywhere, for the genome is part of the common heritage of mankind. But we must not let the excitement obscure the risks and dangers. It will be important, for our species and our society, that law and practices quickly evolve to uphold fundamental values, defend genetic privacy and protect human diversity.
Headlines - National Newsletter.
The Rotary Club of Brisbane West recently donated $2000.00 to the Association with a request that the money be used to purchase 2 pressure relieving mattress overlays for loan to HD clients. The overlays have been purchased and distributed. Our sincere thanks to the Rotary Club for their generosity.
Christmas Hamper Raffle - Drawn 7th December - Jean Batten (Ticket No. 1508) was the lucky winner of this raffle - congratulations Jean. Many thanks to all who supported the Association by selling/buying tickets. Approximately $480.00 was raised.
Aladdin's Bazaar - Sunday 8th April Venue: Bellevue Restaurant, 111 Limestone Street, Ipswich. Please refer to the enclosed flyer for details of the Bazaar.Hedy and Patrick Keogh of Ipswich are involved in staging this event and any assistance you can give them (donation of prizes, volunteering your time, etc.) would be very much appreciated. Please contact Barbara at the office if you can assist.
March 20 Management Committee Meeting - 7.30 pm at HD Centre
March 22 Townsville Family Support Meeting - 7.30 pm at 59 Cambridge Street, Vincent
April 8 ALADDIN'S BAZAAR, 111 Limestone Street, Ipswich
April 10 Bundaberg Family Support Meeting - 7.30 pm at Railway Hotel, Bundaberg
April 17 Management Committee Meeting - 7.30 pm at HD Centre
May 15 Management Committee Meeting - 7.30 pm at HD Centre