Going for the Cure

GOING FOR THE CURE
11th Annual Convention of the Huntington's Disease Society
of America
June 28-30, 1996
Minneapolis, Minnesota

Report by Mary Price

1. General Overview of the Conference

The Huntington's Disease Society of America (HDSA) is dedicated to eradicating Huntington's Disease by promoting and supporting HD research; to helping families cope with the problems presented by HD; and to educating the public and professionals about Huntington's Disease. This three-fold mission was evident throughout the conference as over 500 attendees (including individuals with HD, those at risk, caretakers and health care professionals) were offered over fifty sessions that addressed a wide range of issues pertinent to HD. Those of us fortunate enough to attend this conference came away with a comforting and encouraging sense of belonging to a caring and supportive community, one that is sensitive to the needs of HD patients and families and one that is fully intent on doing all it can do to find a treatment and cure for HD.

The conference started with an opening session on Friday morning (June 28th) where we heard from Mark Anderson (Health Aide to Senator Paul We1lstone, Democrat, Minnesota) who described the legislative actions now pending in the area of health care. Presentations by several HDSA officers and representatives also provided a useful orientation to both the Association and the Conference. Especially noteworthy was the announcement that next year's conference will be hosted by Rochester New York and will be held June 26-29, 1997.

A short closing ceremony was held on Sunday June 30th and in between we were treated to a cocktail party on Friday evening (which included a program by folksinger Charlie Maguire who sang Woody Guthrie songs); this was followed on Saturday by an early morning "Go For The Cure" fun run plus a mid-day luncheon and an evening banquet with dancing; and a non-denominational service was held on Sunday morning (where Carmen Leal-Pock's singing was truly inspirational). These occasions provided ample opportunity for meeting others and for the kind of informal one-on-one conversations that make these conferences so worth while.

This report covers only a few of the conference sessions (primarily those that I and my family attended). These included: HD 101 and 102 (basic information about HD), Current HD Research; and Testing for HD. No attempt has been made to actually summarize the entire contents of any given session; instead, selected highlights are presented which reflect either new information not previously known to me or my family -- or a new way of looking at existing information.

It should be noted that practically all of the speakers reminded their audiences that the information being presented during the conference is based on what is now known about HD (much of it surfacing just during the past 2-3 years since the gene was discovered) and that as new developments are reported, new theories, facts and conclusions will very likely emerge.

2. HD Basics 101

The speaker for this tutorial was Dr. Martha A. Nance, MD. Starting out on an encouraging note, she observed that since 1991 there have been over 400 research papers on HD (which is indicative of the growing attention being given to this neurological disease).

Diagnosis.

A diagnosis of HD is determined by measuring the number of CAG repeats in the Huntington gene. Based on the experiences of the past few years, the "normal" range can be considered to be between 10 and 34 or 35 repeats (with 17 being the most common); and the range of repeats associated with the development of HD can be considered to be 37/38/39 and above -- with a gray area between 34/35 and 37/38/39 where the evidence is inconclusive and where there is overlap between the normal zone and the HD zone.

However, these observations are based on the limited experience of the past three years (since the gene was discovered) -- and the medical profession is still learning and still refining these diagnostic interpretations. It can be stated with a fair amount of reliability that no one has been reported with HD who has less than 34 or 35 repeats. But Dr. Nance noted that the current issue of the American Journal of Human Genetics carries an article which suggests that there is no indication of HD development with 38-39 repeats. At the same time she reported on two patients with 37 repeats: one who has HD at the age of 45 and one who is showing no signs of HD at the age of 77. More experience will certainly help to resolve this particular issue.

With regard to concerns about the gray area, two issues were noted:

There are two different ways to do the gene test: some laboratories isolate only the CAG repeats; other laboratories isolate both CAG repeats and CCG repeats (which are located right next to the CAG repeats on the 4th chromosome). The second method is easier to perform but can result in a slightly higher count. The differences between the two methods are generally irrelevant in those cases where the numbers are clearly in either the normal or HD ranges. However, these differences can be more significant if a count occurs in the gray area (in which case, it is advisable to find out from the laboratory which type of test was performed).
Two properties are acquired by the CAG repeats when there are too many of them: first, they can cause Huntington's Disease; second, as the repeat number goes up, it becomes unstable, allowing for a greater likelihood that the number of repeats will change as the gene is passed from generation to generation. According to this view, an individual with a count in the gray area who does not have HD could pass on a higher repeat count (because of this instability) which could result in a son or daughter with a CAG repeat in the HD range. This phenomenon may help account for those instances of HD that occur suddenly in families with no known history of the disease.

Symptoms.

The dementia that accompanies HD does not appear to be the same as that which occurs with Alzheimer's. With Alzheimer's, that part of the brain which actually stores memory is destroyed. With HD, the actual memory is apparently not destroyed in the same way; instead, it is the neural pathways to the memory that seem to be affected. Therefore, HD patients usually retain the ability to recognize family and friends.
With HD, there is often not so much a personality change as an evolving exaggeration of life-long behavior/personality characteristics.
Weight loss occurs with practically all patients, which means that attention to nutrition and keeping up the patient's weight are important even early in the disease. (This prompted a variation on the good news/bad news jokes: "the bad news is that you have HD; the good news is that you can throw away your diet books")

Pathology.

With HD, loss of cells in that part of the brain called the caudate nucleus occurs. Current thinking indicates that this loss probably occurs as a result of cell death when the Huntington gene binds with a protein -- which results in the cell acquiring a new and harmful function. Dr. Nance demonstrated this theory very vividly using an ax handle as the Huntington gene and an ax blade as the protein. Individually, these are harmless pieces of material; but binding them together produces a potentially life-threatening weapon.

Treatment.

Some doctors discourage the use of drugs for controlling movements early on, because dealing with the early movements is almost considered to be a cosmetic issue. Instead, they wait for later stages when the movements become severe enough to impair function.
There are currently no pills or cures for the dementia; however, there are many medications available to treat behavior disorders that accompany HD.

3. HD Basics 102/Tour of the Brain

Dr. Jane Paulson, MD was the facilitator for this session and she began with a summary of the triad of symptoms that accompany HD: motor, cognition and emotional.

With HD, there is impaired speech expression, but language comprehension remains intact.
With HD, there is impaired learning, but recognition memory remains intact.
Memory and language disappear in Alzheimer's, but not with HD (it just takes longer than usual to retrieve the memory); however, motor memory remains intact with Alzheimer's but not with HD.
With HD there are impaired "executive functions." This includes: impaired decision-making abilities; organizational problems; regulating problems (that is difficulties with temper control; and problems with initiating activities -- which can often be manifested by an appearance of laziness); and awareness problems (such as a denial of deficiencies; unintentional non-compliance; etc.) While these symptoms are social/behavioral in nature, their underlying cause appears to be organic -- due to damage to the caudate portion of the brain.

In reviewing the major parts of the brain (the frontal lobe, cerebral cortex, parietal lobe, cerebellum, etc.) it was noted that the caudate is the part most vulnerable to damage in HD. (However, it can be postulated that something is also going on in other parts since post-mortem examinations seem to reveal that the brains of HD patients tend to shrink and weigh less than non-HD individuals). The caudate runs through the entire brain, and as HD progresses, the caudate is gradually destroyed. Messages and activity between and among the frontal lobe and other parts of the brain pass through the caudate; without the caudate, the pathways for these messages no longer function properly. In other words, the part of the brain that stores information appears to remain fairly intact -- while the pathways via the caudate are what is washed out by HD. The caudate acts as a filter and as a gate-keeper for the brain, helping to regulate and organize actions. HD damage to the caudate leads, among other things, to the impaired executive functions described above.

4. Update on Current Research

With Dr. Nance as moderator, a panel of four individuals provided an overview of new developments in HD research: Dr. Jane Paulson, Dr. Walter Low, Dr. Matthias Kurth and Dr. Nancy Wexler.

Representing the Huntington Study Group, Dr. Paulson reported that current efforts are focusing on three areas:

Providing symptomatic relief for those with the disease;
Protecting nerve cells (including: blocking the effects of excitotoxins; bolstering cell energy production; and scavenging free radicals)
Replacing dead cells with new cells (including fetal tissue transplants)

She also summarized some of the recent achievements of HDSA:

Formulation of the "Unified Huntington's Disease Rating Scale" which all investigators use to judge changes in behavior, movement, function, etc. Use of this scale helps researchers measure the efficacy of experimental drugs in a standardized fashion.
The first multi-center clinical trial for HD which evaluated the benefits of "OPC 14117" on 64 subjects for 20 weeks. OPC 14117 is similar to high dosage vitamin E but it is able to pass through the blood/brain barrier in the brain much more effectively than regular vitamin E. The trials have been successfully completed and the data are now being analyzed.
New clinical trials are being planned for: Co-enzymne Q (which is believed to help in energy metabolism); Remacemide (which may help protect neurons against excitotoxins); and Riluzole (which attacks free radicals and is already being used with ALS patients).

Dr. Nancy Wexler reported with great enthusiasm on a new $10 million collaborative effort between Regeneron Pharmaceuticals and Medtronic, Inc. to develop a potential treatment for HD involving growth factors which might help protect brain cells from HD damage. The particular growth factor being targeted is called CNTF, and the experimental work involves formulating a pump that would be able to get CNTF directly into the appropriate part of the brain where cell protection is needed. As envisioned, the pump could be similar to a pacemaker, and could be worn externally or perhaps implanted internally. Several different groups have been experimenting with animal models, and there should be considerable news about these developments during the next year.

Dr. Walter Low and Dr. Matthias Kurth each reported on experimental work with fetal tissue transplants. Based on the experiments so far, it would seem that animal models work fairly well and that human experiments are encouraging. Addressing in particular the experiments at Good Samaritan Hospital in Los Angeles, Dr. Kurth reported that the progress of the current three patients will continue to be studied -- and that five more transplants will be undertaken, with careful attention to pre-op observations and post-op follow-through.

It was noted that the following areas are candidates for future research:

Predicting the age of onset (based on what is now known, the number of CAG repeats apparently plays some role -- but other factors certainly enter into the picture as well).
Research on the gray area of CAG repeats (especially since new mutations or what have been termed spontaneous occurrences are not as rare as once thought and may be in part a function of gray area repeats).

5. To Test or Not to Test

With Dr. Nance as facilitator, the following opinions or observations were solicited from the audience regarding the highly personal issue of whether to be tested or not:

"I just wanted to know!"

"As long as you're not tested, you have open-ended uncertainty -- and I'm comfortable with that ambiguity."

"As long as you're not tested, you always have the option of being tested; but once you have been tested, you've lost your options."

"By being tested, you reach a certain measure of closure -- and you can better prepare for what may be happening in the future."

"Even with the positive test result, you still have a lot of unknowns, like age of onset and what HD will actually be like for you."

Insurance concerns are common (especially the impact a positive test result might have on future abilities to get insurance).

Regarding the actual gene test, the process usually follows the following steps:

blood is drawn from the patients;
then the white blood cells (carrying the DNA, which contains about 100,000 genes) are separated from the sample;
then using chemicals that recognize certain sequences of letters, the section of DNA that contains the CAG repeat is isolated;
then, another chemical (Taq polymerase) is mixed with the CAG portion of the DNA which, upon rapid heating and cooling, causes that portion to multiply -- thereby providing enough volume to permit visual inspection;
then this enlarged portion of CAG repeats is put on top of some jello-type material in a sieve; as water is poured through it, the smaller genes (the ones with fewer repeats) pass through and go lower while the larger genes (the ones with more repeats) get stuck earlier in the process and remain higher up;
from experience, one can associate repeat numbers (that is, 17, 24, 35, 42, etc.) with the relative vertical locations of the genes in this process. Everyone will have two counts (one from each parent) and only one has to be in the HD zone to be at risk for the disease.

What to look for when selecting a testing site

Personnel who know something about genetics -- and more precisely, personnel who know something about HD (and who are more likely to have access to current information about HD);
Ability to provide genetic counseling;
Awareness of not only the technical issues of the testing process but also the ramifications for the larger picture of the entire family;
Some involvement or association with a physician who knows HD

HDSA can provide a list of testing centers. Cost for the test can range from $500 to $1200. And the elapsed time from the beginning of the testing process to getting the results can range from 3 weeks to 3 months (which includes counseling time). The actual time required for the laboratory procedures is 2-4 weeks.

Converted to HTML by Renette Davis with permission from the author, Mary Price

[Note from the author: This report reflects the hand-written notes of a lay person with an interest in HD. If it contains any mis-interpretations or mis-information, please let me know and corrections can be made. These should be sent to Renette Davis at the address below. Mary Price -- Falls Church, VA]

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