Hormones And MS Research

The clinical course of multiple sclerosis does not appear to be affected by advent of menopause, researchers said here.

The two year change in the Expanded Disability Status Scale increased 0.139 points in a two-year period among pre-menopausal women and 0.122 points in menopausal women (P=0.83), according to Riley Bove, MD, a research fellow at the Multiple Sclerosis Center at Brigham & Women's Hospital and Harvard Medical School.

In reviewing data from the Partners Multiple Sclerosis Center in Boston, Bove and colleagues also found that changes in MRI scans were also similar for both groups of women -- the brain parenchymal fraction declined 0.001 in both groups (P=0.70), and T2 lesion volume decreased 0.002 in pre-menopausal women and increased 0.025 in menopausal women, (P=0.34). Neither change achieved statistical significance.

On the other hand, on the Short Form-36 self-assessment of physical functioning, menopausal women scored lower (P<0.001) than premenopausal women, Bove and colleagues noted in their poster presentation at the American Academy of Neurology meeting.

"There is a scientific rationale for menopause and worsening multiple sclerosis symptoms because menopause modulates other neurologic diseases including dementia, Alzheimer's disease, epilepsy, rheumatoid arthritis and lupus and other inflammatory diseases," Bove told MedPage Today. "So there would be an expectation that it might be similar in multiple sclerosis."

But when the research team looked at hard clinical outcomes such as MRI brain scans, the evidence was not there.

"This data suggest that there is no strong signal for menopause to change the disease course," Philip De Jager, MD, associate professor of neurology at Brigham & Women's Hospital and Harvard Medical School and one of the principal investigators in the study, told MedPage Today.

For the study, the researchers identified 128 women who were pre-menopausal -- ages 38 to 46 -- and 78 menopausal women -- ages 54 to 62 -- with multiple sclerosis. They also compared them with men who had multiple sclerosis -- 41 men ages 38 to 46 and 19 men ages 54 to 62 included in the analysis. Bove said the main purpose of including men in the study was to rule out that any influence age might have on changes in disease course.

In self-reports, menopausal women showed deteriorating symptoms, but men in the same age group did not, raising a signal that menopause might be a contributing factor. "That's kind of what people are seeing in clinic is that women report things that may have more to do with menopause than with multiple sclerosis," she said.

"The next step for us is to actually follow women and men from age of about 40 to 60," she said. "We have a pretty substantial number of people we can follow through the menopausal transition. The symptoms of menopause and peri-menstrual symptoms and all those things are notoriously hard to capture empirically because fluctuating hormones in different people will have contradictory effects."

The researchers said they cannot make strong recommendations for patient management at this time.

"I think it is certainly reasonable to [tell patients] you may experience more fatigue, you may feel worse or you may feel better or it may fluctuate," Bove said. "We should warn them that they may have subjective phenomena but at present there is no data to support that menopause may be making their condition worse."

De Jager has disclosed commercial interests with Merck Serono, Teva Neuroscience and Biogen Idec.

Bove had no disclosures.

Primary source: American Academy of Neurology
Source reference:
Bove R et al, "Menopause may not modulate disease course in multiple sclerosis" AAN 2012; P06.183.

Source: MedPage Today © 2012 Everyday Health, Inc (27/04/12)

Research results indicate that the use of oral contraceptives (OCs) may delay the onset of multiple sclerosis (MS) in women susceptible to the disease.

Previous studies have suggested that sex hormones, particularly estrogen, may influence the pathogenesis and course of MS. Therefore, Per Holmqvist (County Hospital, Sundsvall, Sweden) and colleagues examined the relationships between OC use, childbirth, and MS.

The team surveyed 770 women from the Swedish Multiple Sclerosis Register on their OC use, pregnancies, childbirth, breastfeeding, and medication, as well as age at first symptom and onset (diagnosis) of MS.

The mean age at first MS symptom was significantly higher among women who had used OCs compared with women who had not, at 26 versus 19 years. Indeed, the age at MS onset increased with increasing duration of OC use, from 24 years with less than 1 year of OC use to 32 years with more than 10 years of OC use.

In addition, the mean age at first symptom was significantly higher among women who had given birth before the onset of MS compared with those who had not, at 31 versus 23 years.

"If a protective effect of combined OC could be found on the progress of the disease, this information should be highly relevant when counseling this group of women [susceptible to MS] regarding both their disease and contraception," conclude Holmqvist et al.

Fertility and Sterility 2010; 94: 2835-7

Source: Medwire © 2011 Current Medicine Group Ltd (04/01/11)

In an article published in the January issue of the American Journal of Roentgenology, researchers argue that a spate of recent studies have shown that the hormone might be the first compound after 30 years of testing to protect the brain during acute-stage TBI. And if given to patients in time, the hormone might protect cognitive function and even save lives.

In a recent phase 2 clinical trial with 100 subjects sponsored by the National Institute of Neurological Disorders and Stroke, researchers say patients with moderate-to-severe brain injuries given the hormone intravenously for three days were more than twice as likely to survive: mortality rates were around 14 percent for the hormone versus about 30 percent for placebo.

Another recent study, this one in China with 159 patients, had similar results.

And while the doctors don't know if the findings will apply to humans, work on rats with strokes caused by blocked middle cerebral arteries has shown better brain function following the attack if given the hormone.

This is critical because currently only about 3-5 percent of stroke patients can be treated with tissue plasminogen activators (tPA), a blood thinner that breaks up clots and the only real first-line treatment for strokes currently used. The reason most stroke victims can't get the drug is that doctors have to be absolutely certain the patient is suffering a stroke, otherwise it could cause deadly internal bleeding. And to work, it has to be administered within the first 3½ hours.

Progesterone, by contrast, has shown no adverse effects in any of the studies, and appears to have a wide window, about 24 hours, in which it can work.

How it works

"It's a hormone, in my opinion, that's evolved to protect the fetus," says Donald Stein, Ph.D., a researcher at Emory University and the lead author of the paper. "A lot of mechanisms in repair, not only in the brain but in all highly traumatized tissue, while not identical in development are similar."

The hormone, which can cross the blood-brain barrier, appears to protect neurons in a variety of ways, by preventing injured brain cells from committing suicide and also by blocking the agents that break down their myelin sheaths. But perhaps most critically, it seems to prevent one of the main dangers of brain trauma: swelling.

"One of the things about swelling in the brain, called cerebral edema from, say, injuries in the battlefield, is...that it can kill somebody if not controlled," says Dr. Stein. "And what progesterone has been shown to do effectively is to basically dramatically reduce inflammation and subsequently swelling," he says.

On top of all this, progesterone and its army of metabolites also interfere with glutamate production, a neurotransmitter that floods regions following a trauma. Glutamate, along with other brain chemicals released in injury, can help overexcite the brain and lead to post-traumatic epileptic seizures. That's why progesterone is sometimes given to women with certain forms of seizures to prevent the triggering of debilitating neuronal "electric storms."

Future studies

But how well the hormone really holds up in preventing lasting damage following TBI will be revealed soon. Dr. Stein says a NINDS-sponsored phase 3 double-blind randomized trial, running at 17 centers and expected to handle upwards of 1,200 patients, should start next month.

Source: DOTmed.com ©2001-2009 DOTmed.com, Inc.(30/12/09)

Hormones increasingly are shown to affect brain functions, and now they may battle MS symptoms, too.

When it comes to the brain, hormonal influences are the butt of many tactless jokes and at the heart of Rhonda Voskuhl's seminal findings regarding neurodegenerative disease and protection.

Speeding down the length of the axon, nerve cell impulses, taking a fraction of a second to travel from head to toe, orchestrate choreographed muscle movements. This process is so in sync with our will that most of us can take our ability to walk, see and swallow for granted. But when it breaks down, as it does with the disease multiple sclerosis, unwieldy symptoms emerge.

Paralysis, tingling, uncoordinated movements, blindness and cognitive defects are all symptoms that can coincide with MS — a disease affecting 2.5 million people worldwide. Nerves, normally insulated in white myelin, become demyelinated — exposed —the impulses sputter, dissipate and may never reach their destination. While the immediate cause, scar tissue (sclerosis), will show up in brain scans, the underlying issue is thought to arise from an immune system malfunction (relating to inflammation).

But naturally, it's more complicated than that with environmental as well as hereditary factors as possible contributors to the disease. And, hormones have something to do with it, too.

Research involving hormonal influences on the brain is the rage right now. Yet, while one study suggests hormone therapy in postmenopausal women is detrimental to cognition, another shows memory-enhancing properties in patients with the neurodegenerative brain disorder, Alzheimer's disease. And with regard to MS, the effects of hormones are largely anecdotal. These confounding reports make untangling the specific roles of hormones, and how they relate to disease, challenging.

But Voskuhl's laboratory in the department of neurology at University of California, Los Angeles has taken on the task with vigor. She has received the attention of seven major universities around the country and acquired $5 million in grant money from the National Institute of Health and National Multiple Sclerosis Society to further her research and clinical trials on hormone-related therapy — specifically, therapy using sex hormones.

One of the lab's recent exploratory studies showed that testosterone treatment for men afflicted with MS enhanced cognitive abilities. The therapy also stabilized brain shrinkage commonly associated with the disease. The study investigated the effect of testosterone on 10 men with MS. At the outset, the men showed testosterone levels in the low/normal range. For men, diagnosis of MS tends to coincide with age (occurring between 30 and 40 — a time when available testosterone levels gradually drop). With treatment, the levels rose but not above high/normal quantities.

Analysis from blood showed that testosterone modulates the immune system and enhances production of brain derived protective factors. This supports the idea — central to Voskuhl's research — that hormones have a dual role , anti-inflammatory and neuroprotective, in influencing the disease.

The mechanism for the testosterone results may be due to testosterone's ability to bind brain receptors directly. Alternatively, the brain protection might arise from testosterone conversion to estrogen, a hormone that is routinely generated from testosterone by the enzyme aromatase. Either way, it seems that testosterone (as with estrogen) is neuroprotective. Since MS is a degenerative disease, the ability to target a molecular controller of brain protection would be ideal.

The specific physiological role estrogen plays in disease is also a focus of Voskuhl's investigations. That MS strikes twice as many women as men, along with the phenomenon that pregnant women have a striking 80 percent remission, prompted her to investigate the role of sex hormones in protecting the brain.

Using a mouse model system, Voskuhl and her research team have been able to tease out estrogen's mechanism of action and determine that the neuroprotective attributes can be independent of the inflammation-reducing abilities. This is a remarkable distinction that may guide future therapies. The experiments in mice showed promise for a compound that binds specifically to a distinct estrogen receptor. While the compound is currently not available for clinical use, strategically selecting an estrogen that works through the same receptor is a promising option.

"We've already done a pilot study with estriol," Voskuhl commented. Estriol, a naturally occurring estrogen produced during pregnancy, doesn't have the side effects associated with estrogens traditionally used for hormone therapy. Similar to the testosterone study in men, the pilot trial using estriol in women showed decreases in MS severity. In fact, "the lesions in the brain were reduced by 80 percent," Voskuhl reported.

A larger trial using estriol to treat women with MS is under way. Given as a pill, estriol will provide patients with hormone levels equivalent to six months of pregnancy, since the last trimester of pregnancy is often a time at which MS symptoms improve and relapse rates decrease. The study, currently recruiting participants, will be a two-year placebo-controlled study and will treat patients concurrently with a standard treatment.

Future studies to explore the possibility of using or designing specific compounds that function through the distinct neuroprotective receptor hold promise beyond the standard sex hormones. These designer estrogens may provide long-term protection and be used with standard therapies.

"It's important because anti-inflammatory medications now given reduce symptoms by one-third and have only modest affects on halting permanent disability," Voskuhl noted.

To date there is no cure for the disease. There are six FDA-approved treatment options; many of which act on the immune system. They can alter the disease course, treat specific symptoms and quell disease intensity, but they do not provide the brain with the protection needed to halt, repair or prevent the disease process. The prospect that hormones can decrease inflammation and increase factors associated with promoting brain cell survival is enticing. And the notion that designer estrogens may provide brain protection in MS as well as other neurodegenerative disorders is equally alluring.

As clinicians administer medications and researchers investigate receptors, our nerve cell impulses will continue their journey. And Voskuhl's laboratory will continue theirs. She said, "There are a lot of things that have to be done."

Source:  Miller–McCune © 2008 Miller–McCune Inc. (14/09/08)

Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component. It has been suggested that novel treatment options are needed that target both aspects of the disease.

Evidence from basic and clinical studies suggests that testosterone has an immunomodulatory as well as a potential neuroprotective effect that could be beneficial in MS.

Methods: Ten male MS patients were treated with 10 g of gel containing 100 mg of testosterone in a cross-over design (6 month observation period followed by 12 months of treatment). Blood samples were obtained at three-month intervals during the observation and the treatment period.

Isolated blood peripheral mononuclear cells (PBMCs) were used to examine lymphocyte subpopulation composition by flow cytometry and ex vivo protein production of cytokines (IL-2, IFNgamma, TNFalpha, IL-10, IL-12p40, TGFbeta1) and growth factors (brain-derived neurotrophic factor BDNF, platelet-derived growth factor PDGF-BB, nerve growth factor NGF, and ciliary neurotrophic factor CNTF). Delayed type hypersensitivity (DTH) skin recall tests were obtained before and during treatment as an in vivo functional immune measure.

Results: Testosterone treatment significantly reduced DTH recall responses and induced a shift in peripheral lymphocyte composition by decreasing CD4+ T cell percentage and increasing NK cells. In addition, PBMC production of IL-2 was significantly decreased while TGFbeta1 production was increased.

Furthermore, PBMCs obtained during the treatment period produced significantly more BDNF and PDGF-BB.

Conclusion: These results are consistent with an immunomodulatory effect of testosterone treatment in MS.

In addition, increased production of BDNF and PDGF-BB suggests a potential neuroprotective effect.

Author: Stefan M Gold, Sara Chalifoux, Barbara S Giesser and Rhonda R Voskuhl

Source: Journal of Neuroinflammation 2008, 5:32 (01/08/08)

The Buffalo Neuroimaging Analysis Center is part of the Jacobs Neurological Institute. Located at Buffalo General Hospital, the center has become an international leader in computerized analysis of brain scans.

Most recently, in a study of more than eight hundred MS patients, they've discovered a difference in the way the disease affects the brains of men and women.

Doctor Robert Zivadinov (Buffalo Neuroimaging Analysis Center) said, "We found more gray matter atrophy, and especially cortical and deep brain matter atrophy in men versus women, and that was highly significant."

Gray matter and white matter are the two major components of the brain, and the center's computers can now recognize and measure them.

In one scan, from a man with MS,  the outer folds of brain tissue, called cortex, are separated from each other by dark spaces, because the cortex has shrunk, this is known as atrophy.

In a woman's brain, the spaces are not nearly so wide.

Men with MS become more severely afflicted, perhaps because of a shortage of testosterone.

A recently published study showed that replacement of testosterone in males was protective for brain atrophy in patients who have MS.

Women with MS tend to have more loss of white matter, shown by the enlargement of a central fark area, and that may be related to hormones also, because women with MS don't have acute attacks while they are pregnant.

Gender differences may also explain why certain MS drugs work better in women and others in men.

"I think that we are going to hear more and more about sex influence in MS. Its a totally new, very important chapter."

We've long known that MS affects the brain in different ways, and affects different parts of the brain in different people at different times.

Now, thanks to the computing power and the large number of cases at the Buffalo Neuroimaging Analysis Center, we've learned how it affects women and men differently, and that's useful information.

For instance, Dr. Zivadinov suggests that we might be able to discover whether a sex hormone deficiency plays a role in a particular patient's illness, and do something about it.

Source: WIVB TV News Copyright 2000 - 2008 WorldNow and WIVB (07/05/08)

Testosterone may help treat multiple sclerosis (MS) in men, according to a preliminary study.

It's too soon to recommend testosterone treatment for men with MS, but the findings deserve further study, note the researchers. They included Nancy Sicotte, M.D., of the neurology department at the University of California, Los Angeles (UCLA).

MS is more common in women than men. Sex hormones, such as testosterone, may be partly responsible for the gender gap in MS prevalence, Sicotte's team notes.

Sicotte and colleagues tested testosterone on 10 men with relapsing-remitting multiple sclerosis, the most common form of MS. The men were 29 to 61 years old (average age: 46) and had had MS for about 12 years, on average. They weren't using any  disease-modifying drugs.

At the study's start, the men's average blood testosterone level was on the low side of normal.

First, the men completed a series of mental skills tests and got their brains scanned using magnetic resonance imaging (MRI) technology. The men repeated those tests over the next six months. During that time, they weren't taking testosterone.

After the six-month observation period, the men applied a testosterone gel to their upper arms once daily for a year. Lastly, they repeated the brain scans and mental skills test.

After a year of testosterone treatment, the men's average blood testosterone level was on the high end of the normal range, the study shows.

Testosterone treatment was associated with better scores on the mental skills test and a 67 percent slowdown in loss of brain volume. The men's lean muscle mass also rose with testosterone treatment.

Larger studies are needed to confirm the findings, note Sicotte and colleagues. Their study appears in the Archives of Neurology.

Source: WebMD © 2007, WebMD Inc. All rights reserved.(15/05/07)

Some years back, Dr. Rhonda Voskuhl, director of UCLA's Multiple Sclerosis Program, and her colleagues discovered the cause. They found that a female sex hormone called estriol, which is produced during pregnancy, was responsible for the suppression. Four years ago, Voskuhl followed that discovery with a pilot study in which 10 non-pregnant women with MS were given estriol, yielding what she described as "pretty remarkable" results --- an 80 percent drop in inflammatory lesions in the brain, a hallmark of the disease.

This month, Voskuhl begins a much larger trial of estriol, one that will involve 150 patients at multiple locations over the next two years. The prospects, she said, are exciting.

Multiple sclerosis is an autoimmune disease of the central nervous system that attacks the tissue surrounding the brain's nerve fibres. This tissue, called myelin, can be thought of as the insulation wrapped around an electrical wire. When the myelin is damaged, the nerve's ability to send signals to and from the brain is interfered with, resulting in symptoms common to MS, including problems with balance, memory, vision loss and more.

Currently,  anti-inflammatory drugs used to treat MS lessen the symptoms and slow the progression of the disease. But they must be given by injection daily, weekly or monthly --- depending on the drug --- and are expensive, costing between $12,000 to $24,000 a year.

Estriol is a hormone produced by the placenta that is virtually undetectable until pregnancy, when it progressively increases. It is thought that its role is to suppress a woman's immune system when she is pregnant, so that the fetus will not be seen by the body as a foreign "invader."

"The beauty of estriol is that it can be given as a pill, not a shot, and also that it's not a new drug; it has decades of safety behind it," said Voskuhl, who holds the Jack H. Skirball Chair for Multiple Sclerosis in the UCLA Department of Neurology. For years estriol has been in widespread use in Europe and Asia as hormone replacement therapy for women with menopausal symptoms. The fact that the pill already exists, she said, should dramatically reduce the cost of treatment.

Most important of all, though, is that the drug potentially provides a one-two punch against MS, both reducing the ability of immune cells to attack the brain, as well as making the brain more resistant to damage if any immune cells do make it through.

"It's a two-pronged approach--an anti-inflammatory prong to reduce the attacks, but also a neuroprotective prong to make the brain suffer less damage in case of an attack," said Voskuhl.

In all, seven institutions from around the nation will be involved in the two-year study. The investigators plan to recruit 150 women who have not previously been treated for MS. They will be given either estriol along with Copaxone, an MS drug currently in use, or a placebo along with Copaxone. "That way, no one will receive less than the standard of care," Voskuhl said. The team will measure relapse rates over the course of the trial.

Initial funding of $667,000 for the trial is being provided by the Southern California Chapter of the National Multiple Sclerosis Society. The total cost of the trial is expected to be $4.7 million.

Source: Maxhealth © Copyright 2004-2005 eMaxHealth.com - HealthCare Articles. All Rights Reserved . (10/03/07)

New research offers hope for treatment for multiple sclerosis and other neurological disorders.

The mystery of why multiple sclerosis (MS) tends to go into remission while women are pregnant may be the secret to overcoming the devastating neurodegenerative disease, according to University of Calgary researchers who have shown that a pregnancy-related hormone is responsible for rebuilding the protective coating around nerve cells.

In a paper to be published in the February 21 issue of The Journal of Neuroscience, a team of researchers from the U of C's Faculty of Medicine reports that a study conducted on mice found that the hormone prolactin encourages the spontaneous production of myelin, the fatty substance that coats nerve cells and plays a critical role in transmitting messages in the central nervous system. A collaboration between the laboratories of Drs. Samuel Weiss and V. Wee Yong of the Hotchkiss Brain Institute, the study is the first to determine that prolactin, which increases in the body during pregnancy, is directly responsible for the formation of new myelin in the brains and spinal cords of pregnant mice. Further, when non-pregnant mice with MS-like lesions were injected with prolactin, their myelin was also repaired.

The research was based on evidence that MS, which is more common in women than men, goes into remission when women become pregnant. MS is a neurodegenerative disease where the body's own immune system attacks the myelin surrounding nerves, leading to progressive loss of sensation and movement. MS affects approximately 2.5 million people worldwide and Canadians have one of the highest rates of the disease in the world.

"It is thought that during pregnancy, women's immune systems no longer destroyed the myelin," said Weiss, director of the Hotchkiss Brain Institute and senior author of the study. "However, no previous study has tested whether pregnancy actually results in the production of new myelin, which may lead to improvement of symptoms." The paper's findings represent the first example of a natural, biological mechanism that produces new myelin in the adult brain and spinal cord and identifies prolactin as a potential therapeutic substance for future testing in people with MS.

"Agents promoting remyelination will be beneficial not only for typical demyelinating diseases like MS," says Dr. Fred (Rusty) Gage, of the Salk Institute, "but also for many other neurological disorders, such as spinal cord injuries and stroke." Gage, an international leader in nervous system repair, was not involved in this study.

Subsequent tests of prolactin in animal models of MS will be required before testing of prolactin on humans can take place, but MS researchers are hopeful human trials can take place within the next several years.

"This discovery has the potential to take MS therapy a step further than current treatments that stabilise the disease in its early stages. By promoting repair, which is the goal of prolactin therapy, we have hope of actually improving symptoms in people with MS," says Dr. Luanne Metz, director of the Calgary MS Clinic in the Department of Clinical Neurosciences, University of Calgary and Calgary Health Region.

The study, authored by Weiss, Christopher Gregg, Viktor Shikar, Peter Larsen, Gloria Mak, Andrew Chojnacki and Yong, compared pregnant and virgin female mice of the same age and found that pregnant mice had twice as many myelin-producing cells, called oligodendrocytes, and continued to generate new ones during pregnancy. By chemically destroying myelin around nerve cells, the researchers found that pregnant mice had twice as much new myelin two weeks following the damage as virgin mice and that introducing prolactin mimicked the effects of pregnancy on myelin production and repair in mice that weren't pregnant.

"The results of this study should be well received by people living with MS today," said Dr. William McIlroy, national medical advisor for the Multiple Sclerosis Society of Canada. "It represents a new insight of how we might be able to reverse some of the effects of the disease and improve the quality of life for those who live under its influence." Work needed

John Habkirk, of the Multiple Sclerosis Resource Centre, said: "This research looks to be giving scientific credence to something that people affected by MS have been able to identify for a long time.

"Women nearly always have a much easier time with their MS during pregnancy and at last some research is starting to show precisely why."

MS Trust chief executive Chris Jones said: "It is already well documented that sex hormones such as oestrogen can influence the development and course of MS.

"The suggestion that this can also have a role in replacing myelin is encouraging, but we will have to wait and see if the studies in mice with the experimental equivalent of MS will translate into a successful treatment for people with MS."

MS Society head of research Dr Lee Dunster agreed that the study raised the possibility that prolactin could potentially be used to treat MS.

Source: University of Calgary and BBC Health Copywrite BBC MMVII (19/02/07)

Women produces three kinds of estrogen, estrone (E1), estradiol (E2), and estriol (E3) with the latter increasing substantially during pregnancy. This prompted animal experimentation using a model for multiple sclerosis in mice. Mice treated with estriol actually demonstrated improvements in disability, clinical outcomes and favourable changes in their immune systems. This has prompted human research actually funded by the National Multiple Sclerosis Society to see if administering E3, 8 mg per day (widely available from compounding pharmacies in the United States) will be effective in treating women with the disease.

The study will be carried out by Dr. Rhonda Voskuhl at UCLA. “I am excited by the prospect of finding an easily administered treatment for MS based on a naturally occurring phenomenon in pregnancy. At present the only approved treatments are anti-inflammatory drugs administered with injections,” said Voskuhl, a research scientist at UCLA’s Brain Research and Neuropsychiatric institutes. “Our findings also hold promise for finding new treatments for a host of other autoimmune disorders that improve during pregnancy, such as rheumatoid arthritis.”

Source: Renegade Neurologist - A Blog by David Perlmutter, MD, FACN (30/01/07)

Italian researchers have found that blockade of the hormone leptin, which is primarily produced in fats cells, has beneficial effects on the induction and progression of experimental autoimmune encephalomyelitis (EAE) in mice – the animal model of human multiple sclerosis (MS). In their study appearing online on January 12 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation, Giuseppe Matarese and colleagues from Università di Napoli "Federico II" suggest that leptin neutralization may be a potential way to both prevent and treat MS.

MS is an inflammatory disease of the brain and spinal chord characterized by muscle weakness, numbness, and loss of coordination. These symptoms result in part from destruction of the nerve-insulating material myelin by activated T cells.

Leptin is known to play a critical role in the regulation of food intake, metabolism, and the immune response. Since it had been previously shown that leptin is expressed in active inflammatory lesions of the central nervous system during EAE and MS, Matarese and colleagues investigated the effects of leptin blockade on the induction and progression of EAE in mice. They found that leptin blockade by the use of either anti-leptin antibodies or a form of the leptin receptor unable to bind leptin, either before or after disease onset improved clinical symptoms of disease, slowed disease progression, reduced disease relapses, and reduced the number of antigen-specific T cells. The authors delved further to unravel the cellular signaling events underlying these beneficial effects. Taken together, the data provide a basis for the development and testing of novel strategies of leptin-based targeting for the potential treatment of MS.

Source: Journal of Clinical Investigation (13/01/06)

The hormone DHEA (dehydroepiandrosterone) inhibits experimental MS in mice. It inhibits inflammatory responses and prevents the development of EAE - experimental allergic encephalomyelitis, an animal model of MS.

A group of researchers led by Dr Caigan Du of Vanderbilt University Medical Center in Nashville, Tennessee, found that DHEA led to a significant decrease in T cell proliferation and secretion of nitric oxide and the pro-inflammatory cytokines interferon-gamma, interleukin-12, p40, and tumor necrosis factor-alpha.

Live mice given DHEA had a marked reduction in the severity and incidence of acute EAE.

These findings, Dr. Du and colleagues conclude, show that DHEA has potent anti-inflammatory effects. "Because DHEA does not possess the undesirable side effects of glucocorticoids, it has the potential to be applied to the treatment of chronic inflammatory diseases such as MS."

Ref: Journal of Immunology  (10/01/06)

Experts at Milan\'s Mario Negri institute tested EPO on mice and found that it improves the course of the illness by acting as a neuroprotective agent.

EPO is a hormone produced by specialised cells in the kidneys that regulates the production of red blood cells in the marrow.

Its ability to stimulate the production of red blood cells means it is often used in the treatment of patients suffering from anaemia.

In sports, it is a banned doping agent as it artificially increases the oxygen carrying capacity of the blood and thus improves endurance.

But because EPO thickens the blood, its administration to non-anaemic patients could increase the risk of thrombosis and hypertension.

To avoid unpleasant side-effects, the Milan scientists therefore modified the molecular structure of the hormone into what is known in the scientific literature as CEPO (carbamylated EPO).

CEPO does not increase the number of blood cells but was nevertheless found to be effective when administered to mice suffering from MS.

The finding, published in the December edition of the Journal of Neuroimmunology, mean CEPO may in future be added to the list of MS treatment drugs currently being tested on animals, the institute said in a statement.

MS is a chronic disease that affects the brain and spinal cord. Common symptoms include weakness, depression and difficulties with coordination and speech.

Its causes are unknown and there is as yet no cure.

Source: Monsters and Critics.com © 2005 dpa - Deutsche Presse-Agentur (27/12/05)

The Harvard School of Public Health research showed the incidence of MS was 40% lower in those taking the Pill compared to those who were not.

The findings are in line with previous animal studies which suggested female hormones could delay the onset of MS, or the development of symptoms.

The three year study is published in Archives of Neurology.

MS is an inflammatory disease which causes a range of symptoms from fatigue and numbness to difficulties with movement, speech and  memory.

Pregnancy changes

Researchers compared 106 women who had a new diagnosis of MS between January 1993 and December 2000 with 1,001 other women without MS. Information was taken from the British General Practice Research Database.

Incidence of MS was 40% lower in women using oral contraceptives than in those who were not taking the Pill

Women were also found to have a lower risk of MS during pregnancy, but a higher risk in the six months after having a baby - compared to those who were not pregnant.

Writing in Archives of Neurology, the researchers led by Dr Alvaro Alonso, said: "These findings are consistent with studies on the effect of pregnancy in patients with MS and the immunological changes associated with pregnancy.

"Our findings suggest that high levels of exogenous [from outside the body] oestrogens from OC use and of endogenous [from the body] oestrogens during pregnancy may delay the first clinical attack of MS."

Difficulties

Chris Jones, chief executive of the UK's MS Trust said: "Any new information which highlights potential protective factors for MS is welcomed.

"It is already well documented that sex hormones such as oestrogen can influence the development and course of MS as evidenced by the higher ratio of women with MS compared to men, and the higher risk of MS in women post-pregnancy.

"But it is however difficult to draw firm conclusions from this one study.

"As the authors comment themselves, other factors may have influenced the results, such as a pregnancy during the follow-up period or whether those using the pill were 'healthy' individuals - ie not smokers or overweight.

"Overall, these findings are interesting, although more research needs to be conducted within this area before firmer conclusions can be drawn."

Source: Archives of Neurology (27/12/05)

Women who take the contraceptive pill cut their short-term risk of developing multiple sclerosis by nearly half, according to a survey. The study suggests that the pill could help delay onset of the debilitating neurodegenerative disease.

Birth-control pills contain oestrogen, one of the most significant female reproductive hormones. The compound, whether produced naturally or taken as a pill, helps to regulate the menstrual cycle.

The survey's discovery adds to a range of positive effects that oestrogen has on non-reproductive organs.

The hormone seems, for example, to stop bone loss and forestall heart disease. It can provide relief from hot flushes and may even protect against cognitive decline, although studies linking cancer with hormone-replacement therapy in post-menopausal women have recently curbed medical experts' enthusiasm for oestrogen-containing drugs.

Bad reputation

Roughly two-thirds of multiple-sclerosis patients are female, and women generally have higher levels of oestrogen than men. So the disease has been blamed on the hormone in the past, explains Alvaro Alonso of Harvard School of Public Health in Boston, Massachusetts, who led the recent study.

In fact, some doctors warn women with a family history of multiple sclerosis not to take the pill.

But recent evidence seems to suggest the opposite: mice given extra doses of oestrogen are protected against a neurological disorder similar to multiple sclerosis. Like the human illness, this disease involves destruction of nerve cells' fatty protective coating, called myelin. This layer normally enables these cells to transmit signals hundreds of times faster than their bare counterparts.

With these fact in mind, Alonso and his colleagues conducted an epidemiological study to see whether taking birth-control pills reduced women's risk of developing multiple sclerosis.

Compare and contrast

He and his team used a British research database to identify 106 cases of the disease in women under the age of 50. They then examined prescription records to find out whether the women had received birth control in the three years before being diagnosed. They compared these patients with 1,001 women of similar age in the database who did not develop the neurological disorder. Overall, across all groups, around 5 women in 1,000 develop MS.

The women in this control group were much more likely to be taking oral contraceptives, the team reports in the journal Archives of Neurology¹. Taking the drug reduced the risk of developing multiple sclerosis in the short term by 40%.

"The bottom line is that if a woman wants to take oral contraceptives, that decision shouldn't be influenced by fears of increased risk of multiple sclerosis," says Alonso.

He stresses that the data came from the mid- to late-1990s, a time when UK doctors felt little hesitation in prescribing birth control to patients with a family history of multiple sclerosis, so such fears are unlikely be responsible for the relationship. But he acknowledges that more research is necessary to establish a firm causative link.

Alonso also says that long-term studies suggest oestrogen has no effect on a person's risk of developing multiple sclerosis. He speculates that the protective boost from the hormone lasts only a few years: "If a woman is going to get the disease, in the end she will."

References:  Source - Nature.com ^1.Alonso A., et al. Arch. Neurol., 62. 1362 - 1365 (28/102005).

Researchers say if further studies confirm these results, thyroid hormone may be offered in conjunction with other multiple sclerosis treatments.

To read more Click Here: http://my.webmd.com/content/article/97/103961.htm?lastselectedguid=%7B5FE84E90-BC77-4056-A91C-9531713CA348%7D 

 SOURCE: Fernandez, M. Proceedings of the National Academy of Sciences, Nov. 16, 2004; vol 101: pp 16363-16368. (26/01/05)

They want more research on how all hormones - oestrogens, progesterone, testosterone, prolactin, growth hormone, insulin-like growth factor 1, and other hormones, interact with the immune system in women and men.

The facts they know already about hormones and MS include:

• In MS, women often report a worsening of their symptoms before a period.
• Pregnant women with MS have fewer attacks in the last three months of pregnancy.
• Some animal studies have shown that testosterone can reduce the severity of the animal model of MS.

Trials and results so far include:

1. Women with MS may be successfully treated by the combination of a vaccine and the hormone oestrogen, experiments with mice have shown.

2. Female mice treated with this combination developed fewer MS type symptoms.

3. Used on its own, the vaccine blocks receptors on the surface of the white blood cells, preventing them from attacking the myelin.

4. In clinical trials with MS patients, it has shown modest success in slowing progression of the disease in some patients. But by adding oestrogen, scientists hope the combination of vaccine and hormone will be even more effective.

   It has long been known that pregnant women with MS, when oestrogen levels are high, often go into remission. This led the researchers from the Veteran Administration Medical Center in Portland, Oregon, to find out whether oestrogen could work for women with MS at other times too.

   "When we used combined therapy, the animals were protected and didn't become even mildly ill," said Halina Offner, one of the doctors involved. The team is now considering starting a human trial.

5. At the Department of Neurological Sciences at the University of Rome, they found hormonal fluctuations were significantly associated with MS lesions.

Source: The National MS Society of America (08/06/04)

Dr Rhonda Voskuhl, a neurologist at the University of California, Los Angeles, said: "I am excited by the prospect of finding an easily administered treatment for MS based on a naturally occurring phenomenon in pregnancy. At present the only approved treatments are anti-inflammatory drugs administered with injections. Early treatment is crucial to preventing disabling symptoms. Finding an easily administered oral treatment is important, in part, because patients are less likely to delay treatment if it involves a pill rather than weekly or daily shots."

Oestriol is a weak form of the female hormone oestrogen. It is produced by the placenta during pregnancy. The hormone is used in HRT (hormone replacement therapy) to treat the menopause.

The clinical trial involved 12 women, six with relapsing remitting MS and six with secondary progressive. Ten of the patients completed the trial. Among the relapsing-remitting patients treated with oestriol, researchers found a significant decrease in the number and size of inflammatory brain lesions, an increase in protective immune response and an improvement in cognitive test scores.

When the oestriol treatment ended, the lesions increased to pre-treatment levels. When treatment was re-started, the lesions again significantly decreased. Researchers found no significant improvement in lesions or immune response among the four secondary progressive MS patients who completed the clinical trial.

Larger trials still need to be done to confirm these findings.

Source: Annals of Neurology, October, 2002

Most auto immune system diseases are rare - some very rare - but there are many of those diseases and the overall numbers of sufferers are huge.

Now there's a development which Brisbane researchers say has the potential to change the lives of millions of those sufferers around the world.

When a woman becomes pregnant, her body produces a particular molecule known as early pregnancy factor or EPF. Twenty-five years of work by two Brisbane scientists have culminated in the identification, testing and now production of that molecule.

The research may bring hope to sufferers of auto immune system diseases like Multiple Sclerosis and Rheumatoid Arthritis, and it has the potential also to be developed as an anti-cancer therapy.

In their lab, tucked away in the vast labyrinth of the Royal Brisbane Hospital, doctors Alice Cavanagh and Halle Morton have been quietly working on what's being hailed as a major breakthrough in the treatment of auto immune diseases.

Dr Morton says that when women become pregnant, EPF is produced naturally to stop the body from rejecting or attacking the foetus as a foreign object. She says their research shows it can also stop other cells from doing damage caused by diseases.

Halle Morton says,

Well in Multiple Sclerosis these cells that I was talking about have become activated and recognise parts of the body as foreign and attack them. And in Multiple Sclerosis it's attacking parts of the brain - the membranes that go round the nerve fibres - and this destroys the nerves.

If treatment with EPF would suppress these cells - stop them from recognising this [inaudible] as foreign - and stop damage to the nervous system.

Alice Cavanagh says,

From Halle's original observations in the early 1970s, that there was something in the blood of pregnant animals that affected these white blood cells that made them behave slightly differently.

It actually took almost 20 years to get to the point of identifying what this elusive substance was, and it wasn't until we were able to do that - and that was in the early 90s - that we could then start to move on to this next stage of producing large amounts of the material and actually finding out what it really does - how it works, how we can use it.

So the last - now it's almost 10 years - we've been putting it to the test, and the, the next stumbling block in that process was to move from knowing what it is to making enough of it to do initial studies in animals - which is the stage we're at now - and we'll then need to make the big step of making even larger amounts of it - very large scale production.

There's always the, the thrill of the chase, and a lot of the thrill of science and research is in just finding things out. But to be able to go that step further and actually show that you can apply this directly to people and hopefully help them, is terrifically exciting and satisfying.

And while more research is needed for human trials of the therapy, the potentially lucrative discovery has prompted the formation of the company CBio - which holds the international rights to EPF. CBio owns the international rights to the drug and is hoping to raise five million dollars to begin human trials.

Managing Director, Dr Wolf Hanisch, says the ability to produce EPF on a mass commercial scale is of greater significance than even the actual discovery.

Wolf Hanisch says,

My background's always been in developing drugs back in California in the early days of biotech - long before the Government discovered it.

But EPF had all the hallmarks of some of the great drugs that came out of biotechnology - like erythropoietin EPO that we all know about - drugs like the interferons tissue plas-minogen activator. In other words the drug had gone through an awful lot of testing at the animal scale. It stood out as an obvious, an obvious application and really needed a significant amount of funding to take it through to the next stage which is testing in humans.

PM - Tuesday, August 21, 2001.

© Multiple Sclerosis Resource Centre