Research news - January 2008
Way Ahead 2008;12(1):2-3
- Stem Cell trial underway at Frenchay Hospital
- Early research shows promise for progressive forms of MS
- Participation preferences
- DNA vaccine safe and well tolerated
- Scientists repair myelin in mice
- Researchers warn minocycline can be harmful
- FDA adds new warning to modafinil
- ECTRIMS / RIMS 11-14 October 2007
Stem Cell trial underway at Frenchay Hospital
Six people with MS are undergoing bone marrow stem cell therapy as part of a pilot clinical trial at the Frenchay Hospital in Bristol.
Each of the trial participants received an injection of stem cells derived from their own marrow and are being closely monitored using brain scans and various other assessment tools over the coming 9-12 months.
Leading the trial, Neil Scolding, professor of clinical neurosciences at the Frenchay Hospital and a trustee of the MS Trust, said: 'We believe that bone marrow cells have the capability to repair precisely the type of damage that we see in the brain and spinal cord of MS. So by giving patients very large numbers of their own bone marrow cells we hope that this will stabilise the disease and bring about some repair.'
As the trial is the first to examine the effects of such treatment in people with MS, proving safety and tolerability of the treatment are key considerations. If the treatment proves safe and well tolerated in all six patients, a larger study examining the effectiveness of such treatment in MS is expected to get underway.
Early research shows promise for progressive forms of MS
Preliminary findings of research currently underway at the University of Aberdeen in Scotland are suggestive of an advance in our understanding of progressive forms of MS.
Though still in the very early stages of their research, the team have identified specific antibodies that attack the nerve fibres. These newly identified antibodies are said to recognise and attack a protein called neurofascin-186 which makes up part of the nerve fibre. Crucially, higher levels of these antibodies were found in a small study of people who had a progressive form of MS.
Researchers are now looking to confirm their findings in a larger study. If further evidence emerges to implicate these antibodies in progressive forms of MS, it is believed it may be possible to remove the antibodies from the blood, thus slowing disease progression.
Professor Lington who is leading the research, commented, "I am particularly encouraged because there are already treatments available for other antibody mediated conditions. These type of therapies could be very rapidly translated and applied to MS if we were to confirm our findings."
Participation preferences
A recent study published in the journal Health Expectations revealed an interesting trend in the participation preferences of people with MS. The aim of the study was to determine whether the chronicity of a disease affects patients' desire for participation. The study used the data of 1393 patients from six trials with different medical conditions: hypertension, depression, breast cancer, schizophrenia, MS and minor traumas. No clear differences between chronic and acute conditions were found. However, patients with MS were markedly different from all other diagnostic groups in exhibiting significantly higher participation preferences. The study concluded that the reasons for such differences remain unclear.
Hamann J, Neur B, Kasper J.
Participation preferences of patients with acute and chronic conditions.
Health Expect 2007;10(4):358-563.
DNA vaccine safe and well tolerated
A phase I/II trial testing the safety of a DNA vaccine in a small group of people with multiple sclerosis has produced some promising results. Researchers at the Montreal Neurological Institute, administered BHT-3009 - a tolerizing DNA vaccine encoding full length human myelin basic protein - to 30 patients with either relapsing-remitting MS or secondary progressive MS. Results of the study, published in the Archives of Neurology, indicated that the vaccine was safe, well tolerated and concordant with a reduction of inflammatory lesions on brain MRI. It is hoped that these positive trends will be confirmed in the phase IIb trial that is currently underway.
Bar-Or A, Vollmer T, Antel J et al.
Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial.
Arch Neurol 2007;64(10):1407-15.
Scientists repair myelin in mice
US scientists used a human antibody to promote remyelination in mice with the progressive form of MS. Researchers from the Mayo Clinic in Rochester found that a single low dose of the antibody that was genetically engineered from a single cell, initiated re-growth of the protective myelin sheath. The antibody proved just as effective when administered alongside methylprednisolone - a corticosteroid drug used in the treatment of relapses. Less encouraging was the plateau in the remyelination process that appeared after just five weeks. Further animal tests will follow before the process can be tested in humans.
Researchers warn minocycline can be harmful
Researchers planning to test the acne drug, minocycline, as a potential treatment for a number of neurodegenerative conditions including MS, were warned that the drug could have harmful effects. An article in the Lancet Neurology reported findings of a randomised phase III trial testing the efficacy of minocycline as a treatment for ALS in 412 patients. Compared with the placebo group, the minocycline-treated patients showed a 25% faster deterioration rate on the ALS functional rating-scale. Authors of the paper suggest that trials of the drug in other neurological conditions need to be reassessed.
Gordon PH, Moore DH, Miller RG et al.
Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial.
Lancet Neurol 2007;6(12):1045-1053.
FDA adds new warning to modafinil
The FDA has issued new warnings for an oral drug that is commonly used to treat fatigue in MS. The FDA warns that modafinil (trade name Provigil) can cause rare cases of serious or life-threatening rashes and multi-organ hypersensitivity reactions as well as psychiatric side-effects such as anxiety, mania, hallucinations and suicidal ideation. Patients were advised to stop taking Provigil and consult their doctor if they developed a skin rash or other hypersensitivity reaction. Physicians were also urged to exercise greater caution when prescribing Provigil for patients with a history of depression or mania.
ECTRIMS / RIMS 11-14 October 2007
Nicola Russell, Director of Services, MS Trust
About 5000 delegates attended the European Committee for Treatment and Research in MS (ECTRIMS) and Rehabilitation in MS (RIMS) conference in October. Whilst these are predominantly European meetings, it is interesting that delegates and speakers are now from across the world demonstrating the huge level of research that is currently ongoing and the increased communication and co-operation from all parts of the world.
The key message from the meeting was 'treat early' with aims for the future being to:
- optimise current therapies;
- develop new immunodulatory drugs;
- develop new therapeutic concepts;
- explore combination therapy.
Points of interest include:
- More children are being diagnosed with MS and it is important that these children are managed actively.
- The scales that are used in clinical trials are often inadequate for a condition like MS and much more work needs to take place to find more effective scales. There is also a gap between patient rating scales or patient identification of requirements vs medical measures / functional independence measures.
- Stem cell research is progressing but there is currently still a 3 - 5% mortality risk in the haematopoietic stem cell research.
- Leukaemia is a possible risk with mitoxantrone usage (circa 3%) and needs to be considered alongside the cardiac risks.
- Trials are ongoing with the new oral agent FTY 720 and to date 173 patients have completed 3 years and remain relapse free.
- Further clinical trials are needed to demonstrate the benefit of rehabilitation, and the selection of appropriate patients for rehabilitation.
- The 3-year results of the Alemtuzumab (Campath) study were announced and showed a 73% reduction of relapses compared to high dose Rebif. These results are exceptional considering the patients did not receive their final dose of alemtuzumab due to the trial being stopped following the death which occurred from ITP. Further studies are planned. The Campath research work which has now been ongoing since 1991 shows the need to treat early and the delicate balance which exists between clinical efficacy and potentially serious / fatal side effects.
- Follow up has now been undertaken on the USA trial patients from the original interferon beta 1b trial. The data demonstrates the safety of the agent and also that base line EDSS and MRI predict cognitive deficit at a later time. EDSS was the best predictor of future cognitive deficit.
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