Research news - November 2006
Open Door - November 2006 pages 5-7
- ECTRIMS conference report
- Sleep disturbance and fatigue
- Persistent pain and MS
- Stress and relapses
- Exercising affects the immune system
- Sativex update
- MBP8298 and progressive MS
- Oral fingolimod for relapsing MS
1. ECTRIMS - The European Committee for Treatment and Research in MS
The annual meeting of ECTRIMS took place in the last week of September and saw many of the leading MS experts from across the world meet to discuss the current state of research and treatment. This meeting does not cover rehabilitation.
It is difficult to summarise a three day meeting in a few words but the following topics were certainly under discussion:
- It seems as though the incidence of MS in increasing in women but not men. Further research is underway to support this hypothesis.
- The incidence of MS in children is increasing and possibly 3 - 5 % of the total population of people with MS are now under the age of 16.
- Steroid therapy for relapse management should ideally be started within seven days.
- The role of inflammation and chronic demyelination is still confused, but it is now definite that damage to nerves can start early in the disease process even if clinically the person appears well. Decisions around drug therapy therefore need to be considered sooner rather than later.
- Damage within a lesion seems to be ongoing not a one off event.
- Tysabri usage has now started in Europe and the USA, and the consensus is that providing patients are selected carefully and monitored closely the clinical benefits of this drug outweigh the risks.
- Fingolimod (FTY720) data was presented. This is a new oral drug, which has just completed its early phase II studies. Larger phase III studies are starting and researchers hope to replicate the promising early results. Even if all goes well it would seem unlikely that this product would be licensed before 2010.
- Other new drugs under investigation include: Cladribine, Laniquimod, Teriflunomide, and two as yet unnamed compounds CDP323 and 683699.
- Cannabis remains under investigation for both symptomatic relief and neuroprotection.
The good news from ECTRIMS is that lots of research is ongoing with a variety of different agents. More clinicians and more companies are now working to solve the riddle of MS, which must be good news, although it is clear that the variability of MS makes it a very difficult disease for research trials.
The risk is that in the UK we are getting a second-class service compared with other parts of the world due to our low number of neurologists and completely inadequate budgets.
The MS Trust will continue to campaign on these issues, and we hope our readers recognise the need for ensuring that, if you have MS, you are not subjected to eternal delays with regard to referral and action. Does your GP refer you quickly? Do you get referred to a neurologist who has a real interest in MS? Do you have access to an MS specialist nurse?
If you feel you are not getting the service or information you need do please contact us - we may be able to help.
2. Sleep disturbance and fatigue
This study, looking at sleep disturbance in a group of 60 people with MS, examined the possible causes of sleep disturbance and investigated the link with fatigue. Sleep disturbances were common:
- 42% reported difficulty getting to sleep, most often due to anxiety and pain or discomfort
- 53% reported waking more than twice during the night, mostly due to nocturia (night-time bladder problems), and this was significantly linked with daytime fatigue
- 58% reported waking early
The investigators concluded that sleep disturbance is common in MS, is associated with treatable symptoms such as pain and nocturia and may contribute to fatigue.
Stanton BR, et al.
Sleep and fatigue in multiple sclerosis.
Multiple Sclerosis 2006; 12(4):481-486.
3. Persistent pain and MS
A detailed survey of pain in more than 10,000 people has revealed the high prevalence of severe pain in MS, low satisfaction with management of intense pain, and the effects of pain severity on the respondents' daily life - their work, mood, recreational activities and enjoyment of life. The researchers conclude that healthcare providers need to pay greater attention to the management of pain and uncomfortable sensations in the MS population.
Hadjimichael O, et al.
Persistent pain and uncomfortable sensations in persons with multiple sclerosis.
Pain 2006 Aug 31; [Epub ahead of print].
4. Stress and relapses
In a study of the relationship between stress and relapses, 101 people with MS in Australia were interviewed to assess levels of stress at the beginning of the study and at threemonthly intervals over two years. Stressful events were classed as acute (less than six months duration) or chronic, as well as MS-related or MS-independent.
Overall the results reveal that the impact of life stress on relapse is relatively small and that the long-term stress caused by having MS does not increase risk of relapse. The number rather than the severity of acute stressful events was most closely linked with relapses.
Brown RF, et al.
Relationship between stress and relapse in multiple sclerosis: Part I. Important features.
Multiple Sclerosis 2006; 12(4): 453-464.
5. Exercising affects the immune system
The benefits of exercise, which include improved cardiovascular function, increased strength and endurance and reduced fatigue, are now well established for people with MS. This study looked at the effects of exercise on the levels of cytokines - natural substances that regulate the immune system. Ten women with MS took part in an eight week programme of resistance training. At the end of the training programme levels of some of the cytokines were significantly reduced, while others either showed a non-significant reduction or remained unchanged. Larger studies would be needed to confirm these findings and determine their impact on overall immune function in MS.
White LJ, et al.
Cytokine responses to resistance training in people with multiple sclerosis.
Journal Sports Science 2006; 24(8):911-914.
6. Sativex update
A phase III trial of Sativex, a cannabis based mouth spray, for neuropathic (nerve) pain in people with MS is about to start. The trial will be recruiting in the UK and other countries. For more information, visit GW Pharmaceuticals' website.
GW Pharmaceuticals are seeking a licence for Sativex as treatment for spasticity in people with MS. The application for a licence follows the previous rejection of the drug by the UK regulatory authority. Whilst accepting the safety of Sativex, regulators didn't feel that its effect was proven.
The licensing process will take some time with results not expected until 2007.
Sativex is currently only available in the UK on a named patient basis. For more information, see the MS Trust's Sativex factsheet.
7. MBP8298 and progressive MS
Myelin basic protein (MBP) is believed to be important in the process of myelination of nerves in the brain and spinal cord. Several studies have shown a role for antibodies against MBP in the development of MS. MBP8298 is a synthetic fragment of this protein and is thought to act by causing or restoring tolerance to immune attack at this fragment of MBP.
In this phase II clinical trial, 32 people with progressive MS received an infusion of MBP8298 every six months for 24 months. No significant difference was found between MBP8298 and placebo treatment. However, a statistically significant delay in clinical progression was found in people with certain genetically determined 'HLA' types; HLA are genes located on body cells that help the immune system distinguish between foreign invaders and the body's own tissue. In MS, this distinction doesn't occur and the immune system attacks myelin as if it were foreign. In people with certain HLA types (65-75% of all people with MS), MBP8298 treatment resulted in a delay in progression of MS (78 months for MBP8298 vs 18 months for placebo). A further clinical trial of MBP8298 in secondary progressive MS is currently underway.
Warren KG, et al.
Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment.
European Journal of Neurology 2006; 13(8): 887-895.
8. Oral fingolimod for relapsing MS
Fingolimod (FTY720) is a new oral immunomodulating drug. This phase II trial involved 281 people with relapsing MS who received one of two doses of fingolimod or placebo once daily. At the end of six months, the placebo group was re-assigned to one of the two groups receiving fingolimod. The numbers of MRI lesions were recorded each month.
There were fewer lesions at six months in those receiving fingolimod than those taking placebo; in the follow-up phase, lesion counts remained low in the active drug groups and fell in those previously taking placebo. Larger, longer-term clinical trials are planned.
Kappos L, et al.
Oral fingolimod (FTY720) for relapsing multiple sclerosis.
New England Journal Medicine 2006;355:1124-1140.
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