From the monthly archives: February 2012

 

Ancylostoma caninum, a type of hookworm, attac...

Ancylostoma caninum, a type of hookworm, attached to the intestinal mucosa. Source:CDC's Public Health Image Library Image #5205 (Photo credit: Wikipedia)

Parasitic worms could offer a new treatment hope for patients suffering from the autoimmune disease multiple sclerosis, scientists believe.

Academics at The University of Nottingham have begun recruiting people suffering from the neurological condition on to a trial that will see them infected with a low, harmless dose of the helminth parasite Necator americanus — or hookworm.

The scientists are hoping to prove that the presence of hookworms in the body switches off the mechanism by which the body’s immune system becomes overactive — the main cause of MS — and can reduce both the severity ofsymptoms and the number of relapses experienced by the patients.

The study is being led by Cris Constantinescu, Professor of Neurology in the University’s School of Clinical Sciences and a leading MS expert, and David Pritchard, Professor of Parasite Immunology in the University’s School of Pharmacy, who has spent decades studying the biology of the hookworm.

Professor Pritchard said: ”This study appears counter-intuitive — we are introducing a parasite which is by definition harmful, to act as a stimulus to moderate disease. As a safeguard the hookworms are being used in carefully controlled and monitored conditions, and if successful could herald a much-needed therapy for MS patients.

“Currently, there are many MS patients for whom conventional medicines are ineffective or are associated with unwanted side effects. Hookworms have an innate ability to moderate the immune system to allow them to survive in the body for years. This moderation may have a bystander effect on the progression of MS.”

The study team is in the process of recruiting more than 70 patients from the Nottingham and Derby areas who suffer from the most common type of the disease, relapsing remitting MS (RRMS), in which patients symptoms such as vision problems, dizziness and fatigue, appear and then fade away either partially or completely, and secondary progressive MS with superimposed relapses.

Half of the patients on the trial, funded with £400,000 from the MS Society, will receive a low dose of the hookworms —25 of the microscopic larvae — on a plaster applied to the arm, while the other half will receive a placebo plaster.

Once the larvae come into contact with the skin they work their way through into the blood stream until they reach the lungs where they are coughed up and swallowed to get to their final destination, the gut, where they survive by latching on to the gut lining and feeding on the host’s blood. The worms do not multiply in the host but reproduce by producing fertile eggs, which are expelled in faecal matter. These hatch into infective larvae outside the body, and are used to infect patients.

The patients on the study will be given regular blood tests to check they are not anaemic — a sign that the dose of hookworms could be too high for that individual. Prior safety studies indicate that this is unlikely to happen, and de-worming will take place if it does.

At the beginning of the trial, the participants will undergo a MRI scan to record the scarring or lesions on the brain which are present in MS patients. Over the course of nine months, all the patients will be scanned on a regular basis for new or worsening lesions which can be a tell-tale sign of relapse.

At the end of the trial, the results of the two patient groups will be compared to establish whether the hookworms have been successful in damping down the immune system of the patients, keeping their symptoms in check and preventing relapses.

Professor Pritchard has been studying hookworms for almost two decades since his work as a zoologist took him to remote villages in Papua New Guinea to investigate the parasites in the indigenous population.

Evidence showing that natural parasitic infection led to a lower incidence of other immune-related diseases such as allergy prompted research into the therapeutic potential of worm infection.

Before they were able to put the worms into clinical trial to test their efficacy against human disease, the team needed to establish they were safe to use and had no ill effect while passing through the lungs.

Initially, the researchers volunteered to be infected themselves to establish a safe dosage at which there were no side effects, before participants suffering from asthma and rhinitis were recruited to clinical trials in which they were infected for a period of 12 weeks and studied to ensure there was no effect on respiratory function as parasites migrated through the lungs.

Following the successful outcome of the safety trials, the team has undergone the necessary process of having the hookworms approved as an investigational medicinal product by the Medicines and Healthcare Products Regulatory Agency (MHRA).

Source: PhysOrg.com © PhysOrg.com™ 2003-2012 (01/03/12)

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MS MRIScientists at the University of Nottingham have been awarded £164,000 to test future treatments for people with multiple sclerosis (MS).

A team at the university will use the grant from the MS Society to look at areas of the brain, known as grey matter, that have previously been very difficult to study.

MS is a neurological condition, causing lesions in the brain and spinal cord, which lead to a range of symptoms – including severe fatigue, and problems with mobility and eyesight.

The study will use advanced MRI technology at the university to monitor the grey matter, which has increasingly been shown to be important in MS.

This new information will help researchers to more effectively identify and test new methods for treating damage caused by the condition.

Dr Nikos Evangelou, clinical associate professor of neurology at the university, said: “This study will really advance our understanding of the damage caused in MS and how we might be able to treat it.”

Forty people with MS and ten people without the condition who live in Nottingham will be recruited to the trial, due to start in the next few months.

Findings of the study are due to be published in the next two to three years.

Dorothy Sutton, of the Nottingham Branch of the MS Society, said: “Anything that can speed up the discovery of new effective treatments for people with MS – especially those newlydiagnosed – is really positive.”

Source: This Is Nottingham Copyright © 2012 Northcliffe Media Limited. (29/02/12)

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Avonex PenBiogen Idec said Tuesday that it received U.S. approval for an easier-to-use form of its multiple sclerosis injection Avonex.

The Food and Drug Administration approved the company’s Avonex pen, an injection that is designed to reduce pain and anxiety when patients self-administer the drug. The FDA also approved a new dosing schedule for the drug intended to reduce flu-like symptoms often associated with the drug.

Biogen currently offers a program in which registered nurses visit Avonex patients and teach them to self-inject the original form of Avonex. The drug was approved in 1996.

In a separate announcement, Biogen said it submitted an FDA application for an experimental multiple sclerosis pill known as BG-12. The application consists of two company studies showing reduction in disease activity and favourable safety and tolerability, according to the Cambridge, Mass.-based company. Multiple sclerosis is a disease of the immune system in which the body attacks the brain and spinal cord.

Biogen also markets the multiple sclerosis drug Tysabri with Elan Pharmaceuticals Inc.

Source: Canadian Business © 1999-2012 Rogers Communications.(28/02/12)

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CCSVI VenogramSummary: The authors have designed a study to assess cerebral circulation times (CCTs) in patients with multiple sclerosis (MS) and control subjects by using contrast material-enhanced ultrasonography (US).

The authors have found that the longest and average CCTs were prolonged in patients with MS and that prevalence of CCSVI was higher in patients with MS than in control subjects (77% vs 28%, P < .0001) but no correlation was found between CCTs and clinical status.

The authors conclude that CCT assessment may have a role in the evaluation of cerebral blood flow in patients with MS and that a vascular impairment could be associated with MS but that further evaluation is required, and in particular to determine whether these findings are relevant to neurological outcomes.

Abstract
Purpose: To assess cerebral circulation times (CCTs) in patients with multiple sclerosis (MS) and control subjects by using contrast material-enhanced ultrasonography (US) to determine whether vascular abnormalities can be detected in this disease. Materials and

Methods: This study was approved by the local ethics committee, and informed consent was obtained from all subjects. One hundred three patients with MS and 42 control subjects underwent extracranial and transcranial venous echo-color Doppler ultrasonography (US) and contrast-enhanced US. CCT was defined as the difference in arrival time of the US contrast agent bolus between the carotid artery and the internal jugular vein. The presence of chronic cerebrospinal venous insufficiency (CCSVI) was defined according to previously reported criteria for the extracranial and transcranial US techniques. Nonparametric statistics, including the Mann-Whitney U test and the Kruskal-Wallis analysis of variance, were used to compare contrast-enhanced US parameters between groups.

Results: The longest and average CCTs were substantially prolonged in patients with MS compared with those in control subjects (median longest CCT in patients with MS, 6.47 seconds [range, 3.29-29.24 seconds]; that in control subjects, 5.54 seconds [range, 2.57-7.63 seconds]; P < .001; median average CCT in patients with MS, 5.76 seconds [range, 2.64-17.51 seconds]; that in control subjects, 5.01 seconds [range, 2.57-7.06 seconds]; P < .002). No correlation was found between CCTs and clinical parameters. The prevalence of CCSVI was higher in patients with MS than in control subjects (77% vs 28%, P < .0001). CCT was not significantly different between patients with MS who had CCSVI and patients with MS who did not (P = .182).

Conclusion: These results suggest that contrast-enhanced US with CCT assessment may have a role in the evaluation of cerebral blood flow in patients with MS and that a vascular impairment could be associated with MS. The finding of a prolonged CCT at contrast-enhanced US does not result from outflow impairment. Further studies are required to verify these observations and to clarify if CCT and CCSVI have any physiologic and clinical relevance in MS.

Mancini M, Morra VB, Di Donato O, Maglio V, Lanzillo R, Liuzzi R, Salvatore E, Brunetti A, Iaccarino V, Salvatore M.

Full Article

Source: Radiology. 2012 Mar;262(3):947-55. © RSNA, 2012 & Pubmed PMID: 22357894 (28/02/12)

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Vitamin DExploratory outcomes from a double-blind randomised controlled trial.

Summary: The authors report data from a 96-week randomised controlled treatment trial of vitamin D(3) supplementation on annualised relapse rate (ARR), EDSS, multiple sclerosis functional composite (MSFC) components, grip strength, and fatigue.

In patients with multiple sclerosis supplemented with 20,000 IU vitamin D(3) weekly there was no significant difference in ARR, EDSS, MSFC components, grip strength, or fatigue. Although the study was not powered to address clinical outcomes, none of the results were suggestive of a clinically meaningful effect of vitamin D(3) in this unselected population of fully ambulatory persons with multiple sclerosis.

Abstract
Background: High vitamin D levels may reduce the risk of relapses and disease progression in multiple sclerosis.

Methods: This 96-week randomised controlled trial was designed to assess the effect of vitamin D(3) supplementation on bone mineral density in persons with multiple sclerosis.

Supplementation with 20,000 IU vitamin D(3) weekly raised median serum 25-hydroxy vitamin D (25[OH]D) to 121 nmol/L. The modified intention to treat analysis included 35 persons in the vitamin D(3) group and 33 in the placebo group.

Participants were age 21 to 50 years and fully ambulatory (median Expanded Disability Status Scale (EDSS) 2.5). We studied the effect of supplementing vitamin D(3) on the exploratory outcomes annualised relapse rate (ARR), EDSS, multiple sclerosis functional composite (MSFC) components, grip strength, and fatigue.

Results: After 96 weeks, there was no significant difference between groups in ARR (absolute difference 0.10, 95% CI -0.07 to 0.27; p = 0.25), EDSS (absolute difference -0.01, 95% CI -0.35 to 0.35; p = 0.97), MSFC components, grip strength, or fatigue.

Conclusion: Supplementation with 20,000 IU vitamin D(3) weekly did not result in beneficial effects on the measured multiple sclerosis-related outcomes. This study was not powered to address clinical outcomes, but none of the results were suggestive of an effect in this unselected population of fully ambulatory persons with multiple sclerosis.

Full Text

Kampman MT, Steffensen LH, Mellgren SI, Jørgensen L.

Source: Mult Scler. 2012 Feb 21 Copyright © 2012 by SAGE Publications & Pubmed PMID: 22354743 (01/03/12)

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