A new study sheds some interesting light on the hereditary aspect of MS development, demonstrating that men with multiple sclerosis "pass" the disease onto their children 2.2 times more often than women. This discovery should perhaps be considered alongside another mysterious gender-based fact-- that Multiple Sclerosis is known to affect approximately two times more women than men.

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A new study released today examines scheduled monthly infusions of IV steroids-- rather than dosing on an as-needed basis-- to see if it the regular dosing might be able to prevent relapses. In a very small (9 people!), open label (no placebo) trial, patients underwent monthly MRIs for 6 months, and then began receiving 500mg of steroid (tapered orally for 3 days) for the next 6 months.

The results were quite successful-- 8 of the 9 patients had a reduction in active lesions by a median of ~44%, and T2 lesions (plaques) reduced by ~20%. Treatment was well-tolerated.

Though a weakly-designed trial, it does point out that using steroids as a preventative against relapses might be a decent strategy. It is worth keeping in mind that neither relapses nor lesion load are well correlated with disability progression, asides from a general rule of thumb that the more of either, the worse.

Click "read more" for the full abstract.

A new study examined the effect of the oral anticonvulsant drug Levetiracetam (better known by its brand name of Keppra (r)) on 11 MS patients with intention tremor. Happily, administration of Keppra was associated with an improvement in both subjective and objective tests. Furthermore, the degree of improvement was not associated with the underlying multiple sclerosis disease severity or duration.

Of course, this trial was small, short, and open-label (no placebo arm), so the findings must be considered promising but preliminary. However, given the ready availability of Keppra and the difficulty in managing tremor, this is an interesting study to discuss with one''s doctor when suffering from this particularl symptom of MS.

Click "read more" for the study abstract.

• The Effects of Natalizumab Monotherapy on Multiple Measures of Disability Progression in MS Patients: This one is potentially huge. Of particular interest is the reduction in T1-hypointense lesions, also known as "black holes" which are areas of the brain that are irreversibly damaged. Previously, Copaxone has been shown to reduce these as well, but to a lesser extent than what has been seen with Tysabri in previously announced results (though remember it is difficult to compare trial results directly due to myriad variables).
  
  "OBJECTIVE: To report the effects of natalizumab monotherapy (TYSABRI) on multiple measures of disability and burden of disease in patients with relapsing multiple sclerosis (MS). RESULTS: Over 2 years of treatment in AFFIRM, natalizumab delayed the onset of sustained disability progression by 42% compared with placebo...In addition, natalizumab reduced disability progression as measured by change from baseline in MSFC...the percentage of patients who reached an EDSS of 4.0 (5% vs. 13%...) or an EDSS of 6.0 (2% vs. 6%...), and mean (standard deviation) change in EDSS (0.04 0.86 vs. 0.41 1.09...). Furthermore, natalizumab reduced T2 lesion volume...and the number of new T1-hypointense lesions...over 2 years... CONCLUSIONS/RELEVANCE: Natalizumab monotherapy reduces disability progression and suppresses changes on MRI that represent, in part, irreversible axonal damage in MS."

It seems what was once a piece of useless trivia may become very interesting with respect to multiple sclerosis. Working off the idea that tryptophan may be a powerful immune modulator, new research, from scientists in Germany and California has shown a successful reversal of paralysis in mice afflicted with the laboratory model of Multiple Sclerosis (known as EAE) by dosing the mice with a synthetic version of tryptophan.

The tryptophan synthetic was administered at the onset of paralysis that develops in the animals legs. Compared to placebo animals, the treated mice retained the ability to walk and had fewer and less severe relapses. Furthermore, their immune systems showed a reduction of inflammatory cells considered detrimental to multiple sclerosis patients. Even more intriguing-- when blood was transfused from a treated mouse to a placebo mouse, the recipient actually improved-- implying the change induced by the treatment might be causing the creation of immune cells that target the errant cells responsible for multiple sclerosis inflammation.

The synthetic drug is called tranilast, and is actually used in Japan to treat certain allergy conditions, as well as in various clinical trials worldwide. Certainly the research on mice does not yet indicate that multiple sclerosis patients would benefit from consuming tryptophan or its synthetic derivatives, but it does confirm this relatively common amino acid''s role in mediating the immune system and inspires the evaluation of a potentially straightforward treatment strategy.

As with all animal trials, confirmation of efficacy, and most importantly, safety, needs to be established as a next logical step in the treatment''s development strategy.

Click "read more" for links to source articles...

The results showed that patients taking FTY720 who had originally experienced a reduction in their annualized relapse rate of more than 50% during the first six months of the trial maintained this reduction in the following six months of therapy. In other words, for people who saw benefit in the first six months of therapy, the drug continued to work.

Interestingly, those patients who were originally on placebo during the first six months of the trial and then switched to FTY720 during the latter 6 months showed a 70% reduction in annualized relapse rate.

Finally, greater than 80% of patients on FTY720 for the full 12 months were found to be free from active lesions on their MRIs at the end of the trial.

As we know, a reduction in relapses does not necessarily equate a reduction in disability progression, but it is of course a welcome step demonstrated by this promising data.

Novartis plans to begin Phase III testing by the end of the year, pending FDA approval. If you recall, FTY720 trials were halted after the Tysabri suspension, with the FDA asking Novartis for more information on FTY720''s usage in transplant patients prior to continuation.

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This unique and fascinating study proceeded as follows:

Researchers first gathered fetal neural stem cells, a type of stem cell that is slightly more developed than the usual "blank slate" embryonic stem cells (since they have already become destined to make cells for the central nervous system). On an aside, note that the use of fetal cells is unfortunately bound to be controversial.

The mice "patients" then had their spinal cords "injured" and could no longer walk normally. One should take a moment here to thank these unwitting participants.

Nine days later, some of the mice were injected with the human neural stem cells. Note that the mice were specially bred to not reject human tissue.

After four months, the treated mice could walk normally again, while the untreated mice had not regained their walking abilities!

In a clever twist, the researchers wanted to be sure it was the actual neural stem cells that were causing the improvement, and not some side factor in the mouse itself that was simply invoked in the presence of the stem cells. To do this, they injected the mice with a toxin known to kill human cells but leave mouse cells alone. The result: the mice lost the ability to walk again, indicating that the human neural stem cells were entirely responsible for the restoration of walking ability.

Finally, the cords themselves were analyzed, and the researchers were surprised to see that most of the neural stem cells had formed oligodendrocytes, the myelin "factories" that coat nerve central nervous system axons, providing protection and signal conduction. Again, in MS, a loss of myelin is the most obvious component of the disease.

As usual, more research must be done before testing in humans. The worry is that it is not clear when to inject the stem cells to initaite repair (more of a concern for random spinal injuries as opposed to constant MS attacks on the myelin), as well as how to handle the immune system''s potential rejection of foreign stem cells (remember the mice were specifically bred to not reject human cells).

To that end, lead researcher Aileen Anderson noted, "The last thing we want to do is take someone who''s living a productive life — if confined, we all understand that — and make them worse...The exciting part is the potential is there." (as quoted by by Lauran Neergaard of the Associated Press).

This is truly a very exciting discovery that though distant in clinical applications, sets the stage for the possibilty that myelin repair is attainable using technology that exists today.

Click "read more" for the source article.

More specifically, for patients using topical or internal antibiotics for longer than six weeks, the risk for an infection was two times higher than for non-antibiotic controls. This is relevant for MS''ers using antibiotics as it shows the potential risks of long-term use of the drugs, particularly with respect to giving rise to antibiotic-resistant strains whose activity is theorized to pave the way for other opportunistic viral infections, such as influenza.

For more information, click "read more"...

As quoted by Healthday reporter Steven Reinberg, "MS is more frequent in women than men," said study author Dr. Alvaro Alonso, a research fellow at the Harvard School of Public Health. "Some people have thought that perhaps estrogen can be modifying the risk of MS."

Many oral contraceptives raise the level of estrogens in the body, and it is thought that estrogen has a regulatory effect on the immune system. "We have seen that oral contraceptives can reduce the risk of MS in the short term," Alonso said. "If you are taking oral contraceptives and you are [destined] to have MS, the onset of MS can be delayed one to two years."

That MS risk is lowered during pregnancy-- and in the presence of elevated estrogen levels-- is not entirely surprising. A previous study found that pregnancy was the best treatment for multiple sclerosis.

Despite the findings, Alonso does not see an immediate impact on MS treatments. "The decision to take oral contraceptives or the decision to become pregnant must not be influenced by the idea that this can increase or decrease the risk of MS," he said.

Increasing estrogen levels over the long term can have many undesirable side effects, and is furthermore not feasible for men with MS. As such, further research into the hormonal avenue of treatment will of course be required prior to solid treatment recommendations being produced. This is an area of great research interest-- in particular example, Nicholas LaRocca of the National Multiple Sclerosis Society states: "The society has for several years mounted an ambitious program of research directed at understanding the significance of gender in the pathogenesis of MS. As we continue to learn more about this aspect of MS, it will add to our understanding of the disease and, it is hoped, how best to treat it."

For more information, click "read more"...

"To examine a possible relationship between Chlamydia pneumoniae infection and multiple sclerosis (MS), we undertook an immunohistochemical (IHC), molecular, and ultrastructural comparison of central nervous system (CNS) tissue and cerebrospinal fluid (CSF) sediment from patients with MS and control individuals with other neurological diseases (ONDs)...

Results of studies using these different approaches support our suspicion of the presence of chlamydial organisms in the CNS, in a subset of patients with MS."

Please click "read more" for the full abstract...

A drug wich binds with the alpha (4) beta (1) integrin protein will prevent the immune cell from entering the CNS. The auto-immune theory would then predict that inflammation would be cir*****vented as the immune cells are not present in the CNS to attack myelin.

Tysabri, though currently unavailable whilst the PML issue is worked out, is the first alpha (4) beta (1) integrin binder available for multiple sclerosis patients. A new and very interesting study shows that prolonged exposure to an alpha-integrin inhibitor allows spontaneous remyelination to occur in the mouse model of MS versus vehicle alone (no active drug). In other words, preventing the immune system cells from reaching the CNS allows the body to repair damage better than when the immune cells are present.

Specifically, after 40 days of treatment with an alpha-integrin inhibitor (not necessarily Tysabri, though the study was partially funded by Tysabri''s part-owner Elan...), nearly 90% of the mouse lesions showed some form of remyelination. Further details include the repair occurring in just half of the total lesion areal, and half of the mice regaining motor function lost prior to treatment. The control mice did not show significant signs of repair or regaining of function. The study concludes: "Therefore, prolonged inhibition of CNS inflammation, in the absence of targeted myelin repair, facilitates mechanisms of spontaneous remyelination."

As with any study that is performed on mice, please remember that the mouse model of MS is oftentimes very different than the human version, and thus results on the animals do not necessarily predict results on humans. Likewise, prolonged inhibition of immune cell trafficking might also have unintended consequences, e.g., PML or another new study that shows chronic inhibition initially helps, then exacerbates colitis in mice.

In any case, this is an important study and shows that there is hope for repair of damage, particularly when the immune cells are mostly prevented from trafficking into the CNS.

Click "read more" for the original abstract...

This pilot study from the Mayo clinic explores that very issue. 15 relapsing-remitting MS''ers were given oral (yay!) calcitriol-- a form of Vitamin D prescribed to people who have low levels of calcium in their blood for 48 weeks. The participants were also advised to limit their dietary intake of calcium to prevent skewing the results as well as overdosing on calcium. 13 of the 15 successfully finished the trial, and were examined using expanded disability status scale, MRIs, and clinical examinations.

The results were promising. 4 patients had a total of 5 relapses in the 48 weeks, and 12 of the 13 had their EDSS stay stable within 1 point of starting. MRIs showed enhancing (active) lesions in 5 patients and baseline and 4 at the end of the study.

You know it''s coming: This study showed a positive trend on a safe, easily-administered therapy, but because it is so small-- "more studies are warranted."

Click "read more" for the link to the original abstract.