August 28, 2005

Patient Management in Multiple Sclerosis

Medscape: What are the primary indicators to look for in a patient who is entering into a more progressive form of MS?

Dr. Freedman: Generally speaking, the disease is almost always progressing, but one of our primary concerns is to identify those patients before they experience rapid progression.

The primary indicators to look for include changes in physical exams, cognitive abilities, magnetic resonance images, and electrophysiology. Progression is usually indicated by relapses with a slower recovery time, a shorter time period between relapses, a reduction in the effectiveness of steroids in reducing the inflammation and leading to near complete recovery, loss of endurance, and greater difficulty doing the same tasks. A physical exam might show that there has been some accumulation of a deficit, and, if the Expanded Disability Status Scale (EDSS) is used, it will move in the absence of attacks. These indicators strongly suggest that the patient is entering into a progressive phase....Click to read entire article...Medscape"Multiple sclerosis (MS) is a chronic and often progressive inflammatory disorder of the central nervous system (CNS), and characterizing patient response to various treatments for this disease and monitoring its progression are key to patient management. Medical Editor Penelope Gray-Allan, on behalf of Medscape, discussed patient management and treatment approaches -- presented at the recent meeting of the American Academy of Neurology (AAN) -- with Mark S. Freedman, MD, Professor of Medicine (Neurology), at the University of Ottawa, in Ottawa, Ontario, Canada."

Possible Test May Help Diagnosis MS Early

A More Sensitive Diagnostic Test
A team of medical researchers headed by neurologist Luisa Villar, MD, at the Hospital Ramon y Cajal in Madrid, Spain, wrote in the journal Archives of Neurology that they recently developed a new, more sensitive, diagnostic test to detect levels of IgG in the cerebrospinal fluid of people suspected of having MS. This test "in conjunction with magnetic resonance imaging, can help in the early diagnosis of MS," the study investigators wrote. The aim of this research, therefore, was to determine the efficacy of the test in a group of people diagnosed with various neurologic disorders.

Three-hundred eighty five patients being evaluated in a hospital neurology department were recruited into this observational study. Each patient underwent the OCGB test to search for levels of IgG.

Few False Positives/False Negatives
At the end of the study, Villar and her colleagues found the test was positive for IgG in 127 patients with MS, a 96% sensitivity. The antibody was also found in just over a third of patients with central nervous system infections, and in one patient with motor neuron disease, the investigators reported. There were two patterns uncovered by the test that detected levels of IgG; one pattern showed IgG only in cerebrospinal fluid, which was found predominately in people with MS. The second pattern was found in both cerebrospinal fluid and in blood samples, which was more common in people with central nervous system infections, Villar's group noted.

In all, the test was more than 96% sensitive and had a specificity of over 92%, the researchers reported. When they considered the value of the test in only the MS patients, the study investigators found it still provided 96% sensitivity and more than 99% specificity. Sensitivity represents the probability of a screening test to correctly diagnose a disease. By contrast, specificity represents the ability of such a test to rule out a disease in a patient.

"The accuracy of this OCGB method reinforces the value of cerebrospinal fluid studies in the differential diagnosis of MS," wrote Villar and her colleagues.MS Neighborhood : CLICK

August 27, 2005

Alpha-4 Integrin Inhibitors (e.g., Tysabri) May Sponsor Remyelination

Loosely defined, Alpha (4) beta (1) integrin is a protein on the surface of immune cells that allows them to pass into the central nervous system (CNS). In the auto-immune model of multiple sclerosis, these immune cells then mistakenly attack myelin, causing inflammation and the cascade that leads to scarring (or sclerosis) of the CNS.
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 circumvented 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.This Is MS --...Click to read entire article...

August 24, 2005

Ventricular Function Decreased In Multiple Sclerosis

LINK TO STUDYThere is a decrease in heart ventricular ejection fraction in patients with multiple sclerosis, possibly due to the autonomic impairment associated with the disease. " Autonomic impairment, which frequently occurs in multiple sclerosis patients, may have accounted for the decrease in ventricular ejection fractions. Further physiological studies are required to determine factors responsible for the decrease of ventricular ejection fractions in multiple sclerosis."

August 23, 2005

Daytime sleepiness is not increased in mild to moderate multiple sclerosis

...Click to read...Entrez PubMed
CONCLUSION: In a general sample of MS patients with mild to moderate disease, there was no evidence for overall increased daytime sleepiness compared to healthy controls"

August 22, 2005

MS: Birth order doesn't influence MS risk, study shows

CLICK | Reuters.comContrary to what the "hygiene hypothesis" suggests, the youngest children in a family are not less likely than older siblings to develop multiple sclerosis , new research suggests.

August 21, 2005

Genentech brings Biogen Idec's TYSABRI employees on board

The employees work at the Oceanside biotech manufacturing plant built by Biogen Idec, based in Cambridge, Mass., to manufacture a drug for multiple sclerosis called Tysabri. The company sold the plant to South San Francisco-based Genentech in June for $408 million, after sales of Tysabri were suspended after reports of illness possibly caused by Tysabri.

Genentech is readying the new Oceanside plant to produce Avastin, a drug for colorectal cancer. Avastin belongs to a type of drug known as monoclonal antibodies that precisely target diseased cells.

Biogen Idec built the plant to manufacture Tysabri, also a monoclonal antibody, which relieves symptoms of multiple sclerosis. The plant would have doubled the production capacity for Tysabri, sold by Biogen Idec and the Irish drug company Elan Pharmaceuticals...Click to read...

August 19, 2005

STUDY: Brain atrophy and lesion load in a large population of patients with multiple sclerosis -- Tedeschi et al. 65 (2): 280 -- Neurology

LINKConclusions: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.

August 18, 2005

Multicontrast MRI of remyelination in the central nervous system

link

August 17, 2005

CLINICAL TRIALS OF NEW MS THERAPY: Tovaxin(TM)

LINKPhase I/II clinical trials of Tovaxin(TM), a novel T cell therapeutic vaccine for Multiple Sclerosis, has been accepted for presentation at the 21st Congress of the European Committee/10th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis to be held September 28 - October 1, 2005, in Thessaloniki, Greece. The interim trial results have indicated that the treatment appears safe and well tolerated. In addition to the safety and tolerance indications, the study concluded that MRTCs in patients with MS can be depleted by Tovaxin(TM) treatment. Multiple Sclerosis Impact Scale (MSIS) and Kurtzke Expanded Disability Status Scale (EDSS) clinical measures are improved.

"Having the opportunity to present such encouraging data from Tovaxin(TM) clinical trials at such a prestigious international MS meeting is a great honor and very exciting for our researchers and all of the PharmaFrontiers staff. The acceptance of our abstract confirms our confidence as we move ahead with the development of Tovaxin(TM) for the treatment of patients who are in the early stages of MS," said David B. McWilliams, chief executive officer of PharmaFrontiers. "With our clinical development partner, INC Research, Raleigh, NC, we plan to initiate this pivotal Phase IIb/III clinical study of early relapsing MS patients by the first quarter of 2006 to advance our understanding of this novel T cell therapeutic vaccine for MS." Previous studies of T cell vaccination conducted by Jingwu Zhang, M.D., Ph.D., Director of Research, Baylor Multiple Sclerosis Center at The Methodist Hospital, and colleagues have shown that a monovalent (MBP selected MRTCs) formulation was safe and potentially beneficial in relapsing remitting and secondary progressive patients.

August 16, 2005

MS: Biogen Licenses New MS Drug

Click to read...The deal includes codevelopment rights for Daclizumab, an antibody that has shown promise in preventing transplanted organ rejection and in treating asthma and multiple sclerosis. Positive news about Daclizumab trials underway could bolster Biogen Idec's multiple sclerosis franchise, which has faltered this year since the voluntary suspension of Tysabri, an MS treatment that resulted in unexpected illnesses in several patients who used it during clinical trials.

Copaxone spray clears Alzheimer's brain plaques

Click to read... A new nasal vaccine for Alzheimer’s disease has cleared plaques from the brains of affected mice and will be tested in humans in 2006.They decided on a combination of glatiramer acetate (Copaxone), an approved MS drug that acts as a decoy for errant immune-system attacks, and Protollin, an adjuvant that stimulates innate immunity.

It was given as a nasal mist, a technique Weiner’s lab has had a long interest in. “And it worked,” says Weiner. The combination reduced amyloid beta in the mouse brains by 83% compared to controls.

“The results were quite striking,” says Joanne McLaurin at the University of Toronto, Canada, who has worked extensively on Alzheimer’s vaccines. The idea that inflammation might be helpful in clearing amyloid plaques was first raised a few years ago by a different team, she notes: “The idea is very interesting.”

As always, the question is whether what works in an animal model will work in humans. “Anytime you move from mouse to man there are risks,” says Weiner.

Docs Evaluate Effects of Long-Term MS Therapy of the four different interferon-beta preparations

Click to read... The study, which is still ongoing, is labeled Quality Assessment in MS Therapy, or QUASIMS. "The goal of this study was to compare the efficacy of interferon-beta products in relapsing MS in different clinical settings throughout the world," Limmoth and his fellow investigators wrote. Patients were included in the study if they had been taking one of four interferon betas uninterrupted for at least two years. That included 30 micrograms (mcg) of Avonex (interferon beta-1a) once per week, 250 mcg of Betaseron (interferon beta-1b) once every other day, or two different doses of Rebif (interferon beta-1a): 22 mcg or 44 mcg three times per week.

"Efficacy was similar among patients treated with the four different interferon-beta preparations in different countries," the researchers wrote. "Switching between different interferon preparations did not appear to provide additional benefits."

August 15, 2005

Mayo Docs Predict Which Patients Will Respond to Plasma Exchange for MS....Response to Plasma Exchange for MS Attack Hinges on Pathological Subtype

Click to read...
Differences in the pathological subtype of multiple sclerosis (MS) can predict the response to therapeutic plasma-exchange, a treatment that may restore neurological function after acute MS attacks, say researchers here.

Only patients whose MS lesions have evidence of antibody deposition or complement activation are likely to benefit from therapeutic plasma exchange, reported Claudia Lucchinetti, M.D., of the Mayo Clinic and colleagues in the August 13 issue of The Lancet.

"The new findings may partly explain why some patients respond to a particular treatment and others do not," Dr. Lucchinetti said. "The biological basis for the variable response to current MS treatments is not well understood. It may be that not all MS patients form lesions in the same way and therefore would not be expected to respond to a given treatment the same. Thus, MS treatments may need to be more individualized and tailored for different types of patients."

August 12, 2005

The association of brainstem lesions with migraine-like headache: an imaging study of multiple sclerosis

Click To Read...Headache and Neurology Clinic, University of California-Davis
CONCLUSION: The results of this study indicate that the presence of a midbrain plaque in patients with MS is associated with an increased likelihood of headache with migraine characteristics. (Headache 2005;45:670-677).

August 11, 2005

Stress Influence on MS Relapses

CLICK TO READ ABSTRACTA review of stress%u2013relapse interactions in multiple sclerosis: important features and stress-mediating and -moderating variables

Potential mechanism to repair brain damage linked to MS discovered by OHSU researchers

CLICK TO READ ARTICLEOregon Health & Science University researchers have identified some of the key factors that prevent the repair of brain damage caused by multiple sclerosis (MS), complications of premature birth, and other diseases and conditions. The findings offer important clues about why the nervous system fails to repair itself and suggest ways that at least some forms of brain damage could be reversed. The research is published in the August edition of the scientific journal Nature Medicine.

Anti-myelin antibodies do not allow earlier diagnosis of MS

CLICK TO READ ABSTRACT

August 09, 2005

Questions and Answers on Natalizumab (marketed as Tysabri)

CLICK FOR ARTICLE: U.S. Food and Drug Administration

Elan surges on Tysabri safety study findings

RTE Business -CLICK FOR COMPLETE ARTICLEShares in Elan surged by 20% on the Dublin stock market today after the drugs company and its partner for the development of the MS drug Tysabri, Biogen Idec, said a safety study had resulted in no new confirmed cases of the progressive multifocal leukoencephalopathy (PML) brain disease in MS patients.

The two companies have previously reported three confirmed cases of PML, two of which were fatal.

The ongoing safety evaluation in Crohn's disease and rheumatoid arthritis is on schedule to be completed by the end of the summer, the two companies added. They will then make submissions to regulatory authorities in early autumn.

Elan and Biogen also said that the companies are taking preliminary steps to restart clinical trials in MS.

Study raises hope key Elan drug will make comeback| Reuters.co.uk

click for article: Reuters.co.ukA safety study for Elan Corp.'s (ELN.I: Quote, Profile, Research) (ELN.N: Quote, Profile, Research) multiple sclerosis drug Tysabri has found no new confirmed cases of the brain disease that prompted the Irish company to pull the drug, it said on Tuesday, and its shares soared 21 percent.

MS BREAKING NEWS: TYSABRI: Letter to Healthcare Professionals

From: Gordon Francis, MD, Vice President, Neurology Therapeutic Market, Elan Pharmaceuticals:

"Dear Healthcare Professional,

In an effort to keep you informed of new developments, Biogen Idec and Elan
Pharmaceuticals are providing an update related to the ongoing safety evaluation of
TYSABRI® (natalizumab). On August 9, 2005, we announced that findings from our
ongoing safety evaluation of TYSABRI revealed no new confirmed cases of progressive
multifocal leukoencephalopathy (PML) in multiple sclerosis (MS). The Crohn’s disease and
rheumatoid arthritis safety evaluation is on track to be completed by the end of the summer.

More than 2,000 MS clinical trial patients were eligible for the TYSABRI safety evaluation.
91% of these patients chose to participate in the evaluation. Of these participating patients,
99% had a neurological exam, and 98% had an MRI. The safety evaluation also included the
review of any reports of potential PML in patients receiving TYSABRI in the commercial
setting.

On February 28, 2005, we announced the voluntary suspension of TYSABRI from the US
market and all ongoing clinical trials based on reports of PML, a rare and potentially fatal
demyelinating disease of the central nervous system. The companies have previously
reported three confirmed cases of PML, two of which were fatal. We remain committed to
completing this safety evaluation and look forward to working with regulatory agencies to
determine the appropriate path forward for TYSABRI. Based on expected completion of the
safety assessment by the end of the summer, we anticipate making regulatory submissions to
the U.S. Food and Drug Administration (FDA) by early fall.

Thank you for your patience and continued support over the past few months. We will
continue to inform you of new developments and changes. For additional questions, please
contact Medical Information at"

MS Film nationally recognized

CLICK HERE : PittsburghLIVE.com A 12-minute animation short, "Timmy's Journey to Understand MS," produced by media arts students to help children of multiple sclerosis patients understand the disease, was touted as the Community Service Project of the Year.

August 07, 2005

Docs Identify Possible MS Risk Factor: Viral Antibodies

Click to read complete articleMedical experts have theorized in recent years that the cause of multiple sclerosis may be connected to a viral infection in the body.1-3 Now, a new analysis from doctors at Harvard Medical School suggests that high levels of antibodies that target and attack the Epstein-Barr virus may be the culprit in MS.4

Oral Drug That May Boost Walking Function in MS to be Tested

Click to read complete articleThe medication, labeled Fampridine-SR, is the sustained-release, oral form of the investigational drug, Fampridine. According to its manufacturer, Acorda Therapeutics, the drug is currently being tested in several clinical trials as a therapy for both MS and spinal cord injury. In preclinical trials, the drug has been shown to improve impulse conduction in nerve fibers after myelin has been damaged.

Herschel Walker and His Cycling Team Join Cox MS150 Atlanta Challenge to Beat Multiple Sclerosis!

CLICK FOR FULL ARTICLE

Nurse dedicated life to helping others

CLICK HEREFormer nurse and business owner Lila Burstein managed to achieve several of her life's goals, all while living with multiple sclerosis.

August 06, 2005

Kynurenine metabolism in multiple sclerosis

CLICK
This paper demonstrates the involvement of the kynurenine system in the pathogenesis of MS, which may predict a novel therapeutic intervention.

Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and majo

World of MS - Research - CLICKThis study shows that lymphocyte subsets differ between patients with chronic fatigue syndrome and those with major depression and multiple sclerosis.

Peripheral Cooling May Reduce Tremor Associated With MS

CLICK TO READ ARTICLEPeripheral sustained cooling reduces intention tremor associated with multiple sclerosis (MS), according to the results of a small study published the Journal of Neurology, Neurosurgery, and Psychiatry. The investigators suggest that this may have an immediate clinical benefit.

Pryor's wife says disease saved comedian's life

Click to read article Jennifer Lee Pryor says multiple sclerosis left him in a wheelchair, but also curbed drug and alcohol abuse she's convinced would have left him dead. Instead, he's months shy of his 65th birthday.
Pryor's expletive-laced stand-up act spawned dozens of movies and made him box office magic through much of the late 1970s and early '80s. He's cited as one of the most influential comedians of all time.
Now, Pryor spends most of his time at his home in the hills near Encino, California, with his wife and two rescued dogs.

August 04, 2005

MRI results from the European Study on Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS)

Click to read article Monthly application of high-dose intravenous immunoglobulin (IVIG) to patients with secondary progressive multiple sclerosis (MS) showed no clinical benefit in the European Study on Immunoglobulin in MS (ESIMS)

The mechanism of action of methylprednisolone in the treatment of multiple sclerosis

Click to read articleMethylprednisolone plays an important role in the current treatment of multiple sclerosis (MS), particularly in the acute phase of relapse. It acts in various ways to decrease the inflammatory cycle including: dampening the inflammatory cytokine cascade, inhibiting the activation of T cells, decreasing the extravasation of immune cells into the central nervous system, facilitating the apoptosis of activated immune cells, and indirectly decreasing the cytotoxic effects of nitric oxide and tumor necrosis factor alpha. This paper reviews the most recent observations on these mechanisms both to understand the disease mechanism and its treatment. As more becomes known about these mechanisms, it may become possible to design treatment regimes that are more specific towards both the individual and the disease state.

"Lorain County, home to an unusually high rate of MS will be part of a national study examining factors that may lead to MS"

Click to read complete article: "The study appears to be the first major MS research to consider both genetics and environmental exposure...The study, which begins this week, will focus on 500 people from Lorain County and 20 counties outside Ohio with high rates of MS and exposure to toxic chemicals.

Also in the study are residents in Jackson County, Mo., who were exposed to an oil refinery, and residents of a 19-county area surrounding Lubbock, Texas, who were exposed to a smelting operation."

August 03, 2005

Low Income Patients Get Prescription Drug Help

WECT TV6 LINKLinda Woodall of Wilmington suffers from multiple sclerosis and she has to take more than ten pills a day - and a couple of injections - just to keep the disease at bay.

new, international study suggests that stem cells, the primitive cells that give rise to cells found in the brain, could be the key to treating MS

Click to read complete articleIn the study using a group of mice, researchers at the San Raffaele Hospital in Milan, Italy found that immature nerve cells known as neural stem cells injected into the animals' bloodstreams resulted in suppression of immune attacks that is believed to lie at the heart of multiple sclerosis.

Stem Cells: Myelin Protectors......
The unexpected findings, if confirmed in future research, suggest that these stem cells may not only serve as replacement cells for tissue repair, but may also protect the brain from inflammation.

Recent studies have indicated that Modafinil may prove helpful in easing the extreme fatigue that MS can cause

CLICK FOR COMPLETE ARTICLE

Husbands and Wives Living With Multiple Sclerosis

link...free registration: "The spouses of people with MS play a critical role as caregivers, and their needs must be addressed as part of an overall, effective care plan. The data support the critical need to include spouses in managing the illness, learning advocacy skills, and finding ways to manage the illness. Educating the public about 'invisible symptoms' and reminding businesses to provide for their wheelchair customers would enhance the lives of this population. These data add to nurses' knowledge of what it is like to be the spouse of a person with MS."

August 02, 2005

Elan Still Faces Considerable Uncertainty On Tysabri

link for complete article- Forbes.comMorgan Stanley reiterated an "underweight" rating on Elan (nyse: ELN - news - people ), saying considerable uncertainty still exists around the future of Tysabri, the company's multiple sclerosis treatment.

"We still believe there is significant risk that Tysabri never returns to the market," Morgan Stanley said. The research firm said Elan and partner Biogen Idec have to conduct long-term studies to get the product back on the market, and that if the product does return, safety concerns may minimize its impact on earnings.

Biogen Idec and PDL Form Global Alliance for shared development and commercialization of daclizumab in multiple sclerosis

link: "

August 01, 2005

Assessing the Withdrawal of Natalizumab

Assessing the Withdrawal of Natalizumab - Journal Watch Neurology"The stunning chain of events concerning natalizumab has dealt a shocking blow to many patients who had pinned their hopes on what appeared to be an extremely effective new agent. It also has dashed the hopes of clinicians and discouraged hundreds of natalizumab investigators worldwide. Why PML emerged in patients without other opportunistic infections remains a mystery. JC virus, believed to reside in as many as 80% of clinically asymptomatic adults, probably is harbored in B cells within the bone marrow. It is frequently shed in urine. The mechanism by which it is activated to cause neurologic disease in natalizumab recipients remains unclear and is being investigated."...Dr. Miller is Professor of Neurology, Mount Sinai School of Medicine, and Medical Director, Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York City.