Dr. Lance Meagher, of Cannon Beach, Oregon, claimed that the fertility drug Pergonal halted his ALS. He wrote a paper in 1988 to explain his experience and theory which I have included below. His paper has never been published, as far as I know. I did only minor editing and have added footnotes. Dr. Meagher didn't provide any references or footnotes, and I felt that I couldn't publish his paper without the appropriate notes and corrections.
The organization that gave me this document asked not to be named because it did not support his research financially nor endorse his theory or treatment. You have my permission to reprint and distribute this paper as long as this introduction, the paper, my commentary, and the footnotes are included in full.
Pergonal consists of two hormones: follicle stimulating hormone (FSH) and lutenizing hormone (LH). These hormones are normally produced by the pituitary gland. Dr. Meagher had gradual pituitary failure, and, as he explains in his paper, his ALS stopped progressing when he began taking Pergonal. He attributed this to the FSH, and the theoretical part of his paper is about how FSH may be involved in ALS and why replacing FSH would halt ALS. I've been told that he has passed away since writing his paper, and that his family has moved away from Cannon Beach. Dr. Meagher's sister emailed me when she saw this page and told me he died in 1989 when a home health aid connected the hoses of his ventilator improperly. His death was an accident and doesn't diminish the importance of his discovery.
Even though many of Dr. Meagher's statements are out of date, some are inaccurate, and his theory about why Pergonal halted his ALS can no longer be considered plausible, I think his experience may have other explanations which can help to unravel the mystery of ALS. Meagher was convinced that all cases of ALS are caused by pituitary failure. I think that the cause of ALS varies from patient to patient, and that in many instances there are multiple reasons as to why an individual contracts the disease. It's my opinion that for some, pituitary failure indeed is the primary cause of their disorder and that is why one of these treatments listed, which obviously should be done under a physician's supervision, will save lives and shed much needed light on ALS pathology. See my commentary.
Wayne S. Phillips
Santa Barbara, CA
w%73phillip%73@compu%73erve.com
August 2001
This article tells a story of millions of people and families who have suffered the pain and indignity of ALS. It is also a private and personal story which I reluctantly tell, but now feel I must with the expanding use of FSH. I am now more confident in the efficacy of FSH in the treatment of ALS, but even if I should be wrong, progress has been made.
I have had ALS for 12 years. Average survival is 3 years. My survival alone, while not altogether unknown, is still a distinct rarity, and has convinced some of the validity of my hypothesis. One occasionally finds 10 and 20 year survivors of ALS, but all of them have had the best care, and they have lost all muscles. I am a 12 year survivor, and have maintained most, if not all of my muscles present when therapy was instituted 6 years ago.
Inheritance probably plays a 5% or less role in the pathogenesis of ALS. It is neither contagious nor infectious. Despite exhaustive searches, no evidence to support a viral or slow viral etiology has been found[1]. The immune system is neither hypoactive nor hyperactive[2]. Steroids, which are so useful in autoimmune diseases, have been notably useless, and even dangerous in ALS[3]. The same may be said of antimetabolites. Antibiotics[1], antiviral agents[1], and TRH [thyrotropin-releasing hormone][4] have proven to be no better. Cobra venom is a fraud[5], and its further use smacks of quackery.
There is no reason to believe GH (growth hormone) will be of benefit[6], despite the large, multicenter study which has now begun. No one has found an association between low GH's and ALS. Nor is there any physiologic rationale for the study, other than an inexpensive and plentiful supply of GH. The only possible rationale for its use is that it made us grow when we were young, but this is surely the weakest of reasons.
TRH [thyrotropin-releasing hormone] treatment is fraught with significant side effects[4] There is no physiologic rationale for this treatment, but temporary amelioration of symptoms is found. However, the overall course of the disease is unchanged. It should now be discontinued for the welfare of patients.
I see only permanent side effects, danger and irrationality in the new, million dollar MDA funded study using cyclosporine [7]. Since the most common cause of death in ALS is infection, we need all of our immune system, and then some. French researchers thought perhaps cyclosporine was a panacea for AIDS, and were using it until they found only adverse effects. Needless to say, it is no longer used for that purpose. I find the situations somewhat analogous. About every 5 or 10 years, someone will revive the autoimmune theory in the pathogenesis of ALS. Characteristically, autoimmune diseases respond to immunosuppressant therapy. Abnormal proteins and antibodies are common, as is inflammation. ALS fits none of these patterns[2][8]. It has never responded to steroids [3] or antimetabolites. Although ALS has no qualities of an autoimmune disease, the cyclosporine study will use this most dangerous drug. The March, '87 ANNALS OF INTERNAL MEDICINE demonstrates the extreme likelihood of permanent and progressive renal damage, even when used in non-transplant patients. Randomness seems to be replacing thoughtful research. In this case, I believe the MDA should re-examine their use of funds.
While most of us would try a dangerous drug with promise, only the foolhardy would try such a drug with no prior evidence of benefit in the treatment of ALS. Obviously, the physician must be an educator, and the patient must be inquisitive and somewhat skeptical. Otherwise, the system fails. If one follows some of the above logic, one may as well try a backyard poison.
Since ALS is probably no more common now than before the age of man made pollution, one may assume that ALS is not a man made pollution related problem, although aluminum may or may not be PART of the problem. ALSers do have an abnormally high amount of aluminum in their nerve cells[9]. I now use no aluminum pots or pans, antiperspirants with aluminum (I use only deodorants) or antacids with aluminum.
The development of my treatment was partly fortuitous, as are many of science's novel ideas, but there is also some logic in the analysis, and indeed, my theory fits quite neatly into current, well accepted ideas in neurophysiology. This fact, along with the absence of significant side effects (with the exception of premenopausal women), makes FSH an attractive experimental treatment, at least until its efficacy is disproven. At present, I believe it to be the only treatment with promise of control of the disease. Although all of us must have hope, this treatment still may or may not be effective in ALS. However, should this hypothesis prove true, then results will be beyond comprehension.
The cliche, "Science is only a matter of the right person, being at the right place, at the right time", is certainly applicable to me. ALS is a disease of the elderly, with 90% of the cases being over 60 years of age[10]. Having been fortunate to be the oddball, and acquire this malady at age 29, I have been able to observe this disease process over a much prolonged period of time, perhaps enabling me to see changes not readily apparent during the first few years of the disease. Since I had just finished an internal medicine residency, such observations were greatly facilitated by this recent training.
In my unusual situation, I was consciously poised to observe, analyze and ponder the progress of ALS. Thus, in this situation, at my age, with my training, with a much prolonged case to very closely observe, with this particular disease of which we know so little, combined with several personal and quite timely goals and actions, placed me in a remarkable position for educated observation, indeed, a position that would be most difficult to duplicate. Although unquestionably biased, I believe I can observe subtle changes missed by the physician and ignored by the layman. For the quite long period of 12 years, I have indeed been fortunate to observe and study this disease in totality, as the physician (indeed, the right kind of physician) and the patient, 24 hours a day. I have considered scientific principles, and I have felt tears of despair inherent in the disease. Of course, other physicians have been struck with ALS, but most have been older, their survival shorter, some have been from less related fields, home ventilation is only a recent option (it is still opposed by many), and probably few have had the fortuitous opportunity to use an unusual drug previously unrelated to any neurologic abnormality.
In 1980 I was already a quadriplegic, and nearly ventilator dependent. At that time I had few plans involving significant longevity. The wife and I decided to have a child. Nothing happened. I found myself to have a low sperm count, and we eventually ended at the University of Oregon Fertility Clinic. At each point along a rather torturous path, we were advised against further investigation and/or treatment of the ALS or the fertility problem.
One of the quite rare causes of a low sperm count is a low FSH. I had to find [the cause of] my low FSH. Treatment was further discouraged after consultation with an University of Oregon urologist. Being the typical physician-patient, I began taking injections of FSH (trade name Pergonal) thrice per week[11]. Quite soon, fasciculations noticeably lessened. I have had little, if any progression of my disease since beginning this ongoing treatment with FSH 6 years ago. Any progression I have had, has been during those periods off FSH. Most men with ALS have children already grown, and would never know of their low sperm count, and thus, their low FSH. I have never heard an explanation for Lou Gerhig's childless marriage, but I now have reasonable suspicions.
Pergonal is an approved treatment for specific fertility problems. It has just been approved by the FDA for further experimental use in human ALS patients[12]. FSH is produced in the pituitary gland (a recent CAT scan of mine was interpreted, "pituitary atrophy", a finding previously unfamiliar to me or the literature). Ten years ago, a year after the onset of symptoms, my CAT scan was "normal". I believe the cells in the pituitary which are responsible for FSH production, gradually die in ALS from unknown reasons. I would guess a previous viral infection of the pituitary to be the cause. This hypothesis leads to the conclusion that FSH is not a cure, but a treatment, i.e. there is no reason to believe an injection of FSH will create new FSH producing cells. FSH seems similar to insulin. While not curative, treatment remains necessary. Twelve year old ALS pituitary glands are not very common, hence they probably have not been extensively studied.
It is well known and interesting that ALS is much less common in premenopausal females[13]. Their FSH level is significantly higher than in others. However, my one recent premenopausal patient did indeed, have a low FSH. Again, credence is given to my hypothesis.
In the male, sperm cell maturation takes place in the seminiferous tubules. These tubes are unusual in that they are in a very sequestered environment. Few drugs, proteins or hormones can pass this barrier. Sperm cells must have testosterone to mature, yet testosterone cannot penetrate these membranes. FSH is the key which opens the door to testosterone, and carries it in[14]. This transport by FSH is the only known function of FSH in the male[15]. It has been known for a long time that anterior horn cells are just as sequestered from the rest of the body as are those in the seminiferous tubules[16]. Additionally, several years ago researchers found testosterone receptors on the membranes of anterior horn cells[17], thus proving a roll of testosterone in anterior horn cell physiology. Furthermore, they found a deficiency of these receptors on cells affected by ALS[18]. To try to force testosterone into affected cells, testosterone was given to 4 patients. Two subjects were thought to have no benefit, and two were thought to have definite improvement[19]. Such a small study, over such a short period of time must be judged equivocal, and should be repeated in an expanded and redesigned form. As promising as FSH therapy is, it seems logical to try combination therapy with FSH and testosterone. The only side effect manifest thus far in a few male patients has been a minimal loss of libido. Adjuvant therapy with testosterone (perhaps only in the male) might treat 2 problems at one time.
I. The seminiferous tubules and the anterior horn cells are both similar and unusual in their sequestered status[14][16].
2. FSH is known to occasionally be deficient in man, to the proven detriment of sperm cell production.
3. Testosterone must be essential for the normal function of seminiferous tubules and anterior horn cells[20].
4. Since Clomid did not stimulate pituitary production of FSH, pituitary disfunction must be responsible for FSH deficiency in ALS[21].
5. FSH is necessary for testosterone transport into anterior horn cells and seminiferous tubules[22].
6. My survival is now 12 years on FSH; the national average survival is 3 years. One well known institution recently boasted of its 5 year average.
7. Enough evidence now exists to warrant further study and patient trials.
Chronology of Lance D. Meagher, M.D.:
May '76: Fasciculations first noted.
March '77: Diagnostic hospitalization, St.Vincent's, Jacksonville, Fla. normal EMG & myelogram.
May '77: Dr. Young, Mass Gen Hospital, Boston, ALS confirmed.
July '77: Forced to stop playing violin.
Sept '80 : Married, was a quadriplegic.
April '81: Hospitalized for pharyngostomy, tracheostomy & ventilator placement.
May '81: Low sperm count found.
May '81: Low FSH found.
February '82: I began taking Clomid, but there was no increase in FSH or amelioration of symptoms during the 6 months of treatment, thus leading one to believe the problem is in the pituitary, and not the hypothalamus.
December '82: Began FSH injections, 3 x per week, now every other day with only few interruptions.
November '86 to April '87: Prolonged trial off FSH. Symptoms increase, deficits increase.
April ' 87: Reinstituted FSH. Symptoms decreased in two weeks.
During the last 6 of the 12 year course of my disease, there has been little, if any, progression of my disease. I remain on FSH injections, and my disease remains quiescent. After many trials, I have found that if I go 2 weeks without FSH, I begin to feel a re-emergence of symptoms, but these quickly resolve with renewed treatment.
I have completed a study with Dr. Glen Braunstein, Director of Medicine, Cedars Sinai Hospital, Los Angeles. We had 6 matched controls and 6 ALS patients. Following techniques in the literature, 3cc of blood was drawn every 10 min. for 12 hours. The analysis and computer work were done in Dr. Braunstein's research lab. Controls and patients had FSH values between 3 & 9, with one exception. One patient had a FSH of 14.8, but his triglycerides were quite high at 550 with obvious and marked "milky" serum. This abnormality interferes with FSH measurement. If this subject is not included in the study, the results are highly significant. Our lab has a conversion chart which allows a more accurate final value. In this instance, the high 14.8 would be reduced to 7.4. At this value, the study remains significant. If the value is left at 14.8, then the study becomes insignificant.
As the purist, Dr. Braunstein believes this subject should be included without change. I tend to believe the revised figure should be used. Thus, we are at an impasse of sorts. The obvious solution is to do the study again on a larger scale. This is now being done in a large study in Seattle, Washington.
After hearing of my work, and then seeing the data, they became interested in pursuing my work. They have had an interest in ALS research before. The study will use Ph.D's for several phases of the study. The first part of the study will be done using a new method of measuring the biological activity of FSH in ALS patients and controls. This phase has already begun[23].
Second, post graduate fellows will do work on cadaveric anterior horn cells, especially those from victims of ALS. Third will be a double blind patient trial using Pergonal (FSH). A similar patient trial will be done in Portland [23].
I should report that now my FSH is almost unmeasurable. The books say an isolated low FSH is quite rare. About 75% of my patients have low FSH's, but even those with low normal values have responded to FSH. If one also considers the young woman mentioned above, the evidence for at least an association between ALS and a low FSH becomes irrefutable[24]. Supporting clinical evidence of causality has yet to be substantiated, but proper study is just beginning. However, anecdotal evidence seems quite strong. One could hardly believe 5 random, consecutive ALS patients had low FSH's by coincidence only. It now seems that as the disease progresses with time, the FSH levels continue to decrease (my level is now 0.0). I now think there is more than enough evidence to offer those with ALS a trial of FSH. ALSers from around the country are now being treated with Pergonal, and I now have no idea how many people are receiving this treatment[25]. Of those patients who I personally see, about half believe their disease has significantly slowed or almost stopped its progression, and the other half believe there has been no progression since beginning Pergonal. As previously stated, Pergonal cannot be expected to cure ALS, but I do believe it can arrest further progression of the disease. If a patient is in poor condition, I could not promise great improvement. Two men felt only slight improvement, if any at all. Their Pergonal was increased to every other day, and they were pleased with the improvement.
Results from the Seattle-Portland study should clarify the issue. We shall all cross our fingers.
Lance D. Meagher, M.D.
Cannon Beach Oregon
January 31, 1988
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The majority of the footnotes that have been added seek to amend the incorrect and outdated statements of Dr. Meagher as well as to show why his theory is not plausible. But I didn't publish his paper just to dismantle his theory. I think he's correct that Pergonal did halt his ALS, but that his theory is flawed and that there are other explanations for his success. I want to promote Pergonal and related treatments, but not on the basis of his theory. Many doctors and researchers may dismiss Meagher's experience and theory out of hand when they read the paper, so I will point out the flaws up front, and present other explanations.
To summarize Meagher's faulty assumptions and
conclusion:
1. Testosterone is necessary for the life of motor neurons.
2. FSH is necessary to transport testosterone into motor neurons.
3. Therefore pituitary failure causes low FSH, which in turn causes an
insufficient amount of testosterone to reach the motor neurons, which then
causes their death.
Premise (1) can be disproven by counterexample. There are some men who have "androgen resistance syndrome" due to mutations of their androgen receptor genes. Their bodies are unable to use testosterone, but this doesn't result in their contracting ALS. It should also be noted that castration doesn't cause ALS.
Premise (2), I have been told by my neurologist, isn't true. It is based on a questionable analogy between the blood-testis barrier and the blood-brain barrier. FSH is not necessary for transporting testosterone across either one [14][16].
His conclusion (3) fails due to it's faulty premises, and can also be disproven by counterexample. Many people use Pergonal due to having low FSH, yet their low FSH doesn't cause ALS.
(This implies that low FSH isn't in itself a sufficient condition for ALS. The same is true for LH. I took Pergonal for three months and it didn't halt my ALS. This implies that low FSH or LH isn't a necessary condition for ALS.)
So if we accept Meagher's assertion that Pergonal halted his ALS, but we don't accept his theory, what other possible explanations might there be? For one thing, Pergonal contains both FSH and LH (lutenizing hormone), and Meagher didn't consider the possible effects of LH. Either one may have some direct or indirect neuroprotective effect other than that which Meagher proposed. One possibility has to do with neurosteroids, which are neuroprotective steroid hormones produced in the CNS (central nervous system, e.g. the brain and spinal cord)[26]. Neurosteroids were unknown when Meagher was pursuing an explanation for his results. FSH and LH are peptide hormones, and other tissues that synthesize steroid hormones require a peptide hormone to trigger that synthesis. LH triggers synthesis of androgens in the testes and estrogens in the ovaries. Either FSH or LH may trigger neurosteroid synthesis, and if one were to do so then pituitary failure would leave the CNS vulnerable to various types of damage, and thus contribute to ALS and other neurological diseases and disfunctions. One neurosteroid, progesterone, has direct application to ALS. It's been shown to protect neurons from glutamate excitotoxicity, and glutamate excitotoxicity is now generally accepted to be part of ALS pathology[3]. From the research I've looked over on Medline, neurosteroid researchers haven't pursued which peptide hormone or hormones trigger neurosteroid synthesis. And there are many possible peptide hormones which may be involved other than FSH and LH.
After running all of this by my physician he sent me to an endocrinologist who was open to experimenting with the Pergonal. My endocrinologist said that instead of low hormones causing ALS, that ALS may cause low hormones. He said that when the body senses the stress of a serious illness it decreases the priority of reproduction by lowering production of sex-related hormones, including FSH and LH. My FSH tested very high, but my LH was rather low. He said that my high FSH could be due to damage incurred from chemotherapy with cyclophosphamide, which I had tried. (It failed to halt my ALS.) I took Pergonal for a period of three months and it failed to halt my ALS. My FSH has been high and my LH low ever since that first test, except when on Pergonal.
In the spring of 2000 I was searching the web for information on LH and found information on an Oriental fruit extract called Tribulis. It's supposed to stimulate the pituitary to produce LH. It should be noted that this is not an opinion shared by western science, though it is unlikely that Tribulis has truly been examined for its effects. My wife was able to get Tribulis at our local health food store. (She also received some funny looks apparently because it's considered an aphrodisiac.) I started taking one 625 mg. capsule each morning and within a couple of days felt physically stronger and emotionally better. My LH has been well within normal levels since I started taking Tribulis, but it hasn't halted or noticeably slowed my ALS.
So which ALS patients may benefit from this information? Being that ALS is still very much a mystery it is difficult to say. Not enough is known about this disease to be able to identify a subset of patients who would benefit. The most likely candidates would probably be those who have pituitary failure/atrophy as Dr. Meagher did. But the only way to really tell whom it might help is to try it. And we will not know really whether it's the FSH or LH that is halting the progress of the disease until it is found to work on someone else. I can't recommend treatment, but here is a diagnostic and treatment "path" you can discuss with your doctor. If you pursue this it must be with your doctor's supervision.
1. Get your testosterone/estrogens, FSH, and LH checked. If your testosterone/estrogens are low you may need to watch for osteoporosis. If your FSH and/or LH is low or low-normal then pituitary failure may play a part in your ALS. If they are above low-normal then this probably doesn't apply to you. Remember that if they are low, it may be that the ALS drove your levels down.
2. If your FSH and/or LH levels are low or low-normal then you can test your
pituitary function. The usual test is for your doctor to prescribe Clomid (or
Serophene) which you take orally for several days. Then, when you have
finished, have a blood test done to measure your FSH and LH levels. If your
pituitary is functioning normally then you should have high levels of FSH and
LH. It should be noted that these medicines have been known to adversely
affect ones' mood, at least in women. Also, these meds can increase fertility
in men and women, and increase a woman's chances of pregnancy. See these sites
for more info.
http://www.conceivingconcepts.com/learning/articles/0020.html
http://www.tryingtoconceive.com/clomid.htm
You can also try the fruit extract Tribulis, which is available without a prescription at many health food stores and on the Internet. Tribulis supposedly only affects LH output. Take it for a couple of weeks then get another blood test for FSH and LH. Tribulis may also increase fertility in men and women, and increase a woman's chances for pregnancy.
3. If your pituitary is working and you want to try this line of treatment, you can stimulate your pituitary to put out more FSH and LH over a longer period, one to several months, and see if your ALS halts. You can use Clomid, Serophene, or Tribulis, which are cheaper and easier than Pergonal because they are taken orally. If you use Tribulis and your ALS continues to progress, then you may want to try Clomid or Serophene. If you use one of these, your FSH and LH levels become normal or high, but your ALS continues to progress, then there isn't much point in trying Pergonal. There is an outside chance that one of these meds may halt the illness. They may also slow the progression of the illness, but that is a difficult thing to measure.
4. If your pituitary isn't working properly then you may be the best candidate for this line of treatment. The treatment at this point is to replace the missing or deficient pituitary hormones using Pergonal or similar meds. They are very expensive. You get an injection three days per week or every other day. You or a family member will have to give the injections. Consult with your doctor about whether to use Pergonal or one of it's competitors, and about what period of time it would be reasonable to try it. I took Pergonal for three months, but it didn't halt my ALS. Similar to the meds mentioned previously, these meds increase fertility in men and women, and when women take Pergonal or it's competitors they have an increased chance of multiple pregnancies, e.g. triplets, quads, quints, etc.
Also, if your pituitary isn't working well, you may want to get a CAT or PET scan of your brain to check for "pituitary atrophy." But remember that Dr. Meagher's pituitary atrophy didn't show up until 12 years into his illness.
Good luck, and let me know your results if you try this.
Wayne S. Phillips
Santa Barbara, CA
w%73phillip%73@compu%73erve.com
August 2001
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1. Meagher's information is out of date. Dr. Darryl See found
evidence of echo-7 enterovirus in ALS spinal cord tissue, and Dr. Martina
Berger repeated his results and published them in the January 2000 issue of
Neurology. Prof. Garth Nicolson found mycoplasmas in the blood of >85% of
ALS patients but <9% of healthy controls (unpublished). As of this writing
(August 2001) they are doing a study treating ALS patients who have both
infections with antivirals and antibiotics. In my case an antibiotic and
antiparasitic halted the progress of my ALS. See
treat1.htm
Dr. See's Immune Institute
http://www.immuneinstitute.com
Prof. Nicolson's Institute for Molecular Medicine
http://WWW.IMMED.ORG
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2. Meagher's information is out of date. Dr. Stanley Appel et
al. at Baylor have found auto-antibodies in ALS patients. See their web site
for info and references to published work:
http://www.bcm.tmc.edu/neurol/research/als/als1.html
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3. Meagher's information is out of date. I haven't seen anything that indicates that steroids are dangerous for ALS patients. There is evidence that many steroids are neuroprotective, and I've been taking progesterone for years and it has relieved some of my symptoms and seems to have slowed my ALS.
Steroid hormones protect spinal cord neurons from glutamate toxicity.
Ogata T; Nakamura Y; Tsuji K; Shibata T; Kataoka K
Department of Physiology, Ehime University, School of Medicine, Japan.
Neuroscience (ENGLAND) Jul 1993, 55 (2) p445-9
Progesterone administration attenuates excitatory amino acid responses of
cerebellar Purkinje cells.
Smith SS
Department of Anatomy, Hahnemann University, Philadelphia, PA 19102.
Neuroscience 1991, 42 (2) p309-20
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4. Intrathecal thyrotropin-releasing hormone does not alter
the progressive course of ALS: experience with an intrathecal drug delivery
system.
Munsat TL, Taft J, Jackson IM, Andres PL, Hollander D, Skerry L, Ordman M,
Kasdon D, Finison L.
Department of Neurology, Tufts University, Boston, MA 02111.
Neurology 1992 May;42(5):1049-53
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5. Modified snake venom in amyotrophic lateral sclerosis.
Lack of clinical effectiveness.
Rivera VM, Grabois M, Deaton W, Breitbach W, Hines M.
Arch Neurol 1980 Apr;37(4):201-3
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6. Negative results with growth hormone:
Recombinant growth hormone treatment of amyotrophic lateral sclerosis.
Smith RA, Melmed S, Sherman B, Frane J, Munsat TL, Festoff BW.
Center for Neurologic Study, San Diego, California.
Muscle Nerve 1993 Jun;16(6):624-33
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7. Conflicting results: the first study is negative, the
second positive.
A double-blind study of the effectiveness of cyclosporine in amyotrophic
lateral sclerosis.
Appel SH, Stewart SS, Appel V, Harati Y, Mietlowski W, Weiss W, Belendiuk
GW.
Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
Arch Neurol 1988 Apr;45(4):381-6
Intrathecal cyclosporin prolongs survival of late-stage ALS mice.
Keep M, Elmer E, Fong KS, Csiszar K.
Laboratory of Matrix Pathobiology, Pacific Biomedical Research Center,
University of Hawaii, Honolulu 96822, USA.
Brain Res 2001 Mar 16;894(2):327-31
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8. Meagher's information is out of date. Many researchers
besides Dr. Stanley Appel at Baylor have found evidence of inflammation.
Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in
amyotrophic lateral sclerosis.
Almer G, Guegan C, Teismann P, Naini A, Rosoklija G, Hays AP, Chen C,
Przedborski S.
Department of Neurology, Columbia University, New York, NY 10032, USA.
Ann Neurol 2001 Feb;49(2):176-85
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9. Conflicting results. Many researchers have investigated why there were ALS "hot spots" in Guam and Japan's Kii peninsula. The soil and drinking water in both areas was found to have low calcium (Ca) and magnesium (Mg) and high aluminum (Al) and manganese (Mn). It's been suggested that such trace mineral imbalances may allow Al or other metals to accumulate to toxic levels. Part of this debate is the question, "Do ALS patients have high levels of aluminum in their motor neurons?" The first study, probably done on Japanese patients, says yes. The second study, probably done on Americans, says no.
[Environmental factors in western Pacific foci of ALS and a possible
pathogenetic role of aluminum (Al) in motor neuron degeneration].
[Article in Japanese]
Yoshida S.
Division of Neurological Diseases, Wakayama Medical College.
Rinsho Shinkeigaku 1991 Dec;31(12):1310-2
Aluminum, calcium, and iron in the spinal cord of patients with sporadic
amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a
preliminary study.
Kasarskis EJ, Tandon L, Lovell MA, Ehmann WD.
Department of Neurology, University of Kentucky, Lexington 40536-0084,
USA.
J Neurol Sci 1995 Jun;130(2):203-8
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10. Meagher's information is out of date. Studies that I've
seen each show a different median age of onset, but these median ages are all
in the 50s, so less than half of the cases begin at age 60 or later.
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11. Pergonal is made of follicle stimulating hormone (FSH)
and lutenizing hormone (LH). Meagher doesn't consider the possibility that LH
may have something to do with his results.
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12. I contacted the FDA in the early 90s and they said that
they knew nothing about Pergonal being approved for ALS patients.
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13. Meagher cites no source, but I've heard this from others
and it's what I've observed.
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14. The "sequestering" that Dr. Meagher refers to is
technically known as the "blood-testis barrier." Dr. Judith Gibber of Columbia
University confirmed to me by email that testosterone can passively diffuse
across the blood-testis barrier and doesn't require FSH for transport.
Testosterone (and all steroid hormones) are small, fat-soluble molecules, and
therefore can easily pass through cell membranes and blood-tissue barriers.
Dr. Meagher's assumption may just be outdated.
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15. Again Meagher's information may be outdated. FSH is known to stimulate production of androgen binding protein and testosterone in Sertoli cells, and stimulates activity of the enzyme aromatase which converts androgens to estrogens.
Steroid Hormones
King, MW
http://web.indstate.edu/thcme/mwking/steroid-hormones.html
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16. The "sequestering" that Meagher refers to here is
technically known as the "blood-brain barrier", and testosterone can passively
diffuse through it and through cell membranes surrounding neurons. Again,
there is no need for FSH for transport. My neurologist confirms this.
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17. Meagher doesn't provide a reference, but is probably referring to Sar and Stumpf. But androgen receptors exist inside cells, not embedded in the cell membrane.
Androgen concentration in motor neurons of cranial nerves and spinal
cord.
Sar, M. and Stumpf, W. E.
Science 197 (1977) 77-79
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18. Sar and Stumpf don't report any such deficiency, and I
don't know of any research that does.
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19. Meagher doesn't cite a source, and I don't know of such a study. But research has shown that testosterone and other steroid hormones protect neurons against glutamate toxicity.
Steroid hormones protect spinal cord neurons from glutamate toxicity.
Ogata T; Nakamura Y; Tsuji K; Shibata T; Kataoka K
Department of Physiology, Ehime University, School of Medicine, Japan.
Neuroscience (ENGLAND) Jul 1993, 55 (2) p445-9
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20. It is true that testosterone is necessary for
seminiferous tubules to function properly, but Meagher only assumes it to be
true of anterior horn cells. This can be disproven by counterexample. There
are some men who have "androgen resistance syndrome" due to mutations of the
androgen receptor gene. Their bodies are unable to use testosterone, but this
doesn't result in their contracting ALS. It should also be noted that
castration doesn't cause ALS.
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21. Meagher seems to assume that pituitary failure is the
cause of all ALS. This seems to be true in Meagher's case, and may be true for
some other patients. Other ALS patients may have hypothalmic failure, and some
ALS may have nothing to do at all with the hypothalmic-pituitary-gonadal axis
(HPG axis). The hypothalamus produces gonadotropin releasing hormone (GnRH).
GnRH triggers the pituitary to produce FSH and LH.
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22. This is not true for either the seminiferous tubules or
anterior horn cells[14][16].
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23. I contacted sources in Oregon and at the University of
Washington and haven't been able to find any information about these followup
studies. Dr. Braunstein is also not aware of any followup studies.
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24. There does seem to be a correlation between ALS and FSH,
but that doesn't tell us which is cause and which is effect. My
endocrinologist said that instead of low testosterone causing ALS, that ALS
may cause low testosterone. He said that when the body senses stress of a
serious illness it decreases the priority of reproduction by lowering
production of sex hormones.
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25. I haven't been able to find anyone else who is using or
has used Pergonal for ALS.
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26. Neurosteroids: a new function in the brain.
Baulieu EE
Communications Hormonales (U 33) INSERM and Biochimie Hormonale,
Faculte de Medecine Paris-Sud, Bicetre, France.
Biol Cell 1991, 71 (1-2) p3-10
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