Vanguard Neurologist

From bloomberg.com

Patients in the early stages of multiple sclerosis had their disability reversed in a study that used their stem cells to “reset” their malfunctioning immune system.

All 21 patients in the study at Northwestern University in Chicago had the “relapsing-remitting” form of the disease that makes their symptoms alternately flare up and recede. Three years after being treated, on average, 17 of the patients had improved on tests of their symptoms, 16 had experienced no relapse and none had deteriorated, the study found.

“This is the first study to actually show reversal of disability,” said Richard Burt, an associate professor in the division of immunotherapy at Northwestern, and the lead author of the study published today in the British journal, the Lancet. “Some people had complete disappearance of all symptoms.”

In multiple sclerosis, or MS, a patient’s immune cells attack the central nervous system, degrading their vision, coordination, balance and sometimes their cognitive abilities.

The vast majority of patients with this disease are first diagnosed with the relapsing-remitting form and some progress to more serious stages. The study included only patients whose flare-ups continued after being treated with protein-based drugs known as interferons.

Participants had their hematopoietic, or blood-forming, stem cells extracted before chemotherapy drugs killed immune cells in their bone marrow. The patients’ stem cells were then returned to rebuild their marrow.

Vision Dimmed

One of the patients was Edwin McClure, now a 24-year-old graduate student in marketing at Virginia Commonwealth University in Richmond. McClure was diagnosed with multiple sclerosis as a high school senior in 2002, after his vision dramatically worsened.

“It was like someone had turned down the dimmer switch,” he said in a telephone interview yesterday. He also suffered from dizziness, poor balance and fatigue so bad that he’d collapse and sleep for three hours every day after school.

Over the next few years, McClure was treated with steroids and interferons. While they controlled the disease for a time, his symptoms eventually broke through, triggering fresh attacks.

McClure went to Chicago to take part in Burt’s study at the end of 2005, spent a month being treated, and hasn’t needed any drugs since.

‘A Blessing’

“It’s a blessing,” he said. “My disease has been halted.”

Even the stress of being in the competitive graduate program — a factor known to exacerbate symptoms of multiple sclerosis — hasn’t caused a single attack, he said. His balance is better and his vision hasn’t deteriorated further.

Researchers believe that in the early stage of the disease, the hyperactive immune cells attack nerve cells. This damages the myelin, an insulating material that surrounds the axons, long fiber tails that extend from a neuron and help transmit electrical signals.

“Research has shown it’s critical to stop the inflammation early and that’s probably the best way to stop neural degeneration and progression of the disease,” said Patricia O’Looney, vice president of biomedical research at the National MS Society, in a telephone interview yesterday.

In previous efforts, Burt and other scientists tried giving bone marrow stem cells to patients with more advanced disease, with no benefit.

Late-Stage Failure

“I called it a failure,” he said. “When you do it in late-stage patients, they don’t improve,” probably because the immune cells have already done their damage.

O’Looney said the results of Burt’s study were promising and should now be replicated in a larger trial that randomly compares the stem-cell treatment with existing therapy. Burt is now starting such a trial, which will recruit 55 patients in the U.S., Canada and Brazil.

If the results of today’s study are borne out in the new one, “I think we can really change the way this disease is approached,” Burt said.

By David Perlmutter, MD, FACN, ABIHM

Recently, the most convincing data ever presented relating infection with a specific organism to multiple sclerosis has been reported from the Department of Neurology and Pathology, Vanderbilt School of Medicine, Nashville, Tennessee. Dr. Subramaniam Sriram and coworkers, publishing their results in the Annals of Neurology, have demonstrated the presence of a specific type of bacteria in 100% of the 37 multiple sclerosis patients they studied. As the authors reported, “The evidence of Chlamydia pneumoniae in both progressive MS and relapsing-remitting patients suggests that the infection of the central nervous system with Chlamydia pneumoniae occurs early and persists perhaps throughout the course of the disease and does not differentiate between different clinical subtypes of the disease.” This purported relationship between risk for multiple sclerosis and infection with Chlamydia pneumoniae was recently substantiated in a study appearing in the March 2003 issue of Epidemiology. In this report, Harvard researcher Kassandra Munger found a 70% increased incidence of multiple sclerosis in women seropositive for the presence of Chlamydia pneumoniae antibodies. This organism is a fairly recent addition to the list of bacteria known to affect humans. It is now recognized as a cause of pneumonia, pharyngitis, bronchitis, and several chronic diseases. More importantly, Chlamydia pneumoniae has now been recognized as playing at least some causative role in reactive arthritis and coronary artery disease – medical conditions which, like MS, are characterized by ongoing inflammation.

The idea that multiple sclerosis may be caused by some form of infectious agent is supported by several interesting observations. On the Faroe Islands prior to 1920, MS was essentially unknown. Subsequent to the invasion of British troops, the incidence of MS increased dramatically. This would support the contention that MS, at least on the Faroe Islands, was caused by some infectious agent to which the native population had not been previously exposed. In addition, the cerebrospinal fluid (CSF) in patients with documented multiple sclerosis, is typically found to contain high amounts of specific proteins known to be elevated in other nervous system disorders in which infectious causes have been clearly identified. If there is such a strong relationship between the presence of Chlamydia pneumoniae and multiple sclerosis, how could its presence have been missed by researchers for so many years? The answer lies in the fact that the discovery of Chlamydia in the spinal fluid of MS patients required the development of a very sophisticated test to detect a unique protein found on the cell wall of the Chlamydia pneumoniae organism itself. Indeed, this is not the first example of a profound delay in the identification of an elusive bacterium as the cause of a specific illness. It has been only in the past few years that the bacteria Helicobactor pylori has been demonstrated to be the causative agent in most cases of gastric ulcers. Incredibly, Helicobactor pylori has been identified in the stomachs of humans since the early 1900s, but medical researchers couldn’t bring themselves to admit the possibility that a disease like gastric ulcers could be caused by a simple bacterium.

Another observation supporting the relationship between Chlamydia pneumoniae and multiple sclerosis is based on the discovery that two commonly used medications for multiple sclerosis, interferon-beta and methotrexate, profoundly inhibit the growth of the Chlamydia bacterium. This is interesting and provocative information as we don’t yet fully understand why these drugs are sometimes effective in MS treatment. Over the past several years, the medical literature has published various articles describing specific viruses thought to be the causative agent for multiple sclerosis, only to have these reports subsequently refuted. But this new research describing the possible relationship between Chlamydia pneumoniae and multiple sclerosis is most compelling. And the good news is that unlike viruses, specific antimicrobial medicines are available to treat Chlamydia pneumoniae. Based upon this research, it is not unreasonable for patients with multiple sclerosis to consider an empiric treatment for Chlamydia pneumoniae. As this discovery is relatively new, no specific treatment protocols have as yet been created. And it will likely be several years until clinical trials have been designed, approved, funded, completed, and ultimately published, until we know for sure that MS patients should be treated. But in light of the present evidence, empirically treating MS patients for Chlamydia pneumoniae seems reasonable. Obviously this decision should be discussed with the treating physician. Antibiotics generally quite effective in treating Chlamydia pneumoniae infections include minocycline and tetracycline. Minocycline may be the more effective treatment since it is more able to penetrate the blood-brain barrier to enter the brain. The Perlmutter Health Center protocol for the empiric treatment of Chlamydia pneumoniae in our MS patients is: Minocycline 100 mg twice a day for 21 days.

Again, the decision to engage in this empiric treatment should be made after patient and physician consider the literature linking Chlamydia pneumoniae to multiple sclerosis, as well as the potential risks of taking a course of minocycline or other antibiotic. It is always important when taking any antibiotic to also use a probiotic. These are nutritional supplements designed to reestablish appropriate levels of the “friendly bacteria” in the gut like Lactobacillus acidophilus and others which aid in the absorption of nutrients, help maintain the integrity of the gut lining, and assist in detoxification.

From BBC NEWS

Mice given the equivalent of six to eight cups of coffee a day were less likely to develop a disease similar to multiple sclerosis, a study found.

Researchers hope this could lead to new ways to prevent MS in humans.

The Proceedings of the National Academy of Sciences journal reported that the caffeine appeared to prevent nervous system damage.

However, experts recommend no more than five cups a day, amid evidence higher doses can worsen diabetes.
While the chain reaction which leads to multiple sclerosis is still not fully understood, a key moment surrounds the entry of immune cells into the central nervous system.

Once there, they trigger “autoimmune” attacks, gradually and progressively destroying the fatty myelin sheaths that protect nerves.

Current treatments for MS are limited only to slowing the progress of the disease once it is established.
At Cornell University in the US, and Turku University in Finland, the researchers are using a mouse disease called “experimental autoimmune encephalomyelitis”, or EAE, to mimic the development of MS in humans.

One of the effects of caffeine in both mice and humans affects a molecule called adenosine, which plays a role in sleep and energy production.

When mice were dosed with caffeine, adenosine could not link to a particular receptor on the surface of cells.

This in turn appeared to have an indirect effect on the ability of immune cells to enter the nervous system at a part of the brain called the choroid plexus, and the mice did not develop EAE.

While the precise reason this happened was not clear, the researchers suggested the adenosine blocking effect led to a lower number of “adhesion molecules” – needed by the immune cells to gain entry – on the surface of the choroid plexus.

Risks and benefits

Dr Linda Thompson, who led the study, said that the next step was to see if humans who drank plenty of coffee showed any signs of being less prone to MS.

“If you found a correlation between caffeine intake and reduced MS symptoms, that would point to further studies in humans.”

However, even if this were established, coffee might not be a good way to prevent MS.

The six to eight cups given to the mice is above the limit set by the Department of Health.

Other research has suggested that it might be physically addictive at these levels, and might worsen the control of type II diabetes, a far more common disease of older people.

A spokesman for the MS Society was also cautious: “Over the years there have been numerous discoveries that have prevented EAE in mice but turning this into effective therapies for humans remains a challenge.

“Based on the results of this study, we wouldn’t advise people to change their caffeine intake.”