Currently there are no disease modifying treatments available for people with secondary progressive MS (SPMS). This study looked at the effect of high dose of simvastatin in people with SPMS. Simvastatin is already licensed for lowering "bad" cholesterol in the blood and so is used to reduce the risk of heart disease and stroke.
140 people with SPMS in London and southeast England, either took a high dose of simvastatin (80mg a day) or a placebo for two years. MRI brain scans showed that for the group taking simvastatin, there was significantly less reduction in brain volume, when compared to the group that had taken a placebo.
The authors concluded that high doses of simvastatin might be a treatment option for SPMS. However there is not sufficient evidence from this small study alone to confirm that it would be an effective treatment, so further larger phase III clinical trials would be required.
Currently there are no disease modifying treatments available for people with SPMS. All of the current disease modifying treatments available for people with MS, work principally through reducing the rates of relapses. In SPMS, the frequency of relapses decreases but the level of disability starts to increase. It is thought that this is due to increasing loss of nerves, which show as a brain volume loss on MRI scans, and so researchers have been trying to find a treatment that can help people with SPMS.
How this study was carried out
140 people with SPMS in London and southeast England, either took a high dose of simvastatin (80mg a day) or a placebo for two years. At the start of the trial all participants were aged 18-65, had not taken any disease modifying drugs or immunosuppressants for six months and had not had a relapse or used steroids in the last three months.
Also all participants, had a diagnosis of SPMS and had an Expanded Disability Status Scale (EDSS) score of between four and six and a half. The EDSS is a commonly used measure of disability in MS. A score of four indicates a significant disability but the person is self-sufficient and able to walk without aid or rest for 500m. A score of six and a half indicates that the person requires two walking aids, such as a pair of canes or crutches, to walk about 20m without resting.
Through the trial MRI brain scans were used to measure brain volume, levels of disability were assessed using the EDSS and participants completed several questionnaires that examined the impact of MS on their daily lives.
What was found
In the group that had taken simvastatin for two years, there was significantly less reduction in brain volume, when compared to the group that had taken a placebo. Smaller but still significant effects on two of the disability measures were also found, there was a slower change in EDSS and improved scores in the MSIS-29 questionnaire, which measures the impact of MS on daily life. However no change was found in the frequency of relapses or the scores on the MS Functional Composite Scale (MSFC), which is a measure of mobility, dexterity and cognition.
What does it mean?
The study shows that high doses of simvastatin for two years appeared to reduce brain volume loss in people with SPMS. Although the researchers do caution that just because a difference is found on a brain scan, this does not necessarily mean that there is a noticeable difference in a person's symptoms.
The authors concluded that high doses of simvastatin might be a treatment option for SPMS. However there is not sufficient evidence from this small study alone to confirm that it would be an effective treatment. Further larger phase III clinical trials would be required to investigate the use of simvastatin further.
This study has encouraging results, but the trial was in a small number of people and further larger trials are needed and these will take some time, as trials need to be run for a few years. Statins, including simvastatin, are already licensed in the UK for lowering levels of "bad" cholesterol, but they are used as a much lower dose than the doses used in this trial. Further trials would assess the safety as well as the effectiveness of treatment. So it is unclear whether simvastatin will eventually become a treatment for MS.
Chataway J, Schuerer N, Alsanousi A, et al.
Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. .
Lancet. 2014 Mar 18. [Epub ahead of print]
Read the full text of this paper
More about developing new treatments
The development of new drugs is a long and difficult process. Only one or two compounds in 10,000 tested actually make it through to being licensed treatments. A potential new medicine may be rejected at any point in the development process on safety, effectiveness or quality grounds. Overall, it may take 10-15 years for a new compound to get from the test tube to the medicine cabinet.
Drug licenses are granted for a specific use and in a particular group of people. However clinical trials will continue after a medicine has been granted a license, as the drug may have uses as a treatment for other conditions and these can be tested. If the results of these further trials show the drug has a use in other conditions, an application can be made for the regulator to extend the terms of the current license to the new condition.
Even though a drug may already have a license and be proven to be an effective treatment in one condition, the trials to investigate its use in another condition can still take many years.
There are three types of drug trial:
- Phase I – the first step in testing a new drug is to determine the safety of single doses in a small number of healthy volunteers.
- Phase II – if the treatment proves to be safe, studies begin to determine the effectiveness of the drug in people with the condition to be treated. These studies may last several months or years and involve larger numbers of people, perhaps one or two hundred.
- Phase III – if a drug shows effectiveness, a larger study is conducted in hundreds of people. These clinical trials take place at different locations and across several countries and may last several years. These studies allow researchers to more accurately assess the potential of the new drug in a wider range of people and compare it to existing treatments.
Drug treatments for secondary progressive MS
The trial reported here investigated simvastatin, which is part of a class of drugs known as statins. Lower doses of simvastatin are widely prescribed, like other statins, to lower "bad" cholesterol in the blood. High levels of "bad" cholesterol are thought to lead to hardening and narrowing of the arteries so increasing the risk of heart attacks and stroke.
There are other additional drugs that are currently licensed for other conditions which are being tested in SPMS. These are amiloride, ibudilast and riluzole. These are being tested as part of a phase II trial, called MS-SMART, which will study 440 participants over two years.
There are also several other drugs that are still experimental that are being investigated and trialled as treatments for SPMS. These are masitinib, natalizumab (Tysabri) and siponimod. Further details and updates will be posted on the MS Trust drugs in development webpage.
Research by topic areas...
Symptoms and symptom management
Mahadeva A, Tanasescu R, Gran B.
Urinary tract infections in multiple sclerosis: under-diagnosed and under-treated? A clinical audit at a large university hospital.
Am J Clin Exp Immunol. 2014 Feb 27;3(1):57-67.
Disease modifying treatments
Lee DH, Stangel M, Gold R, et al.
The fumaric acid ester BG-12: a new option in MS therapy.
Expert Rev Neurother. 2013 Aug;13(8):951-8.
Drugs in development
Olsson T, Boster A, Fernández O, et al.
Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial.
J Neurol Neurosurg Psychiatry. 2014 Mar 21.[Epub ahead of print]
Read the full text of this paper
Ciurleo R, Bramanti P, Marino S.
Role of statins in the treatment of multiple sclerosis.
Pharmacol Res. 2014 Mar 20. pii: S1043-6618(14)00027-9.[Epub ahead of print]
Giovannoni G, Gold R, Selmaj K, et al.
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial.
Lancet Neurol. 2014 Mar 18. pii: S1474-4422(14)70039-0.[Epub ahead of print]
Complementary and alternative medicine in multiple sclerosis.
Neurology. 2014 Mar 25;82(12):e103-7.
Yadav V, Bever C Jr, Bowen J, et al.
Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis: report of the Guideline Development Subcommittee of the American Academy of Neurology.
Neurology. 2014 Mar 25;82(12):1083-92.
Eyssen IC, Dekker J, de Groot V, et al.
Client-centred therapy in multiple sclerosis: more intensive diagnostic evaluation and less intensive treatment.
J Rehabil Med. 2014 Mar 24.[Epub ahead of print]
Lamers I, Feys P.
Assessing upper limb function in multiple sclerosis.
Mult Scler. 2014 Mar 24. [Epub ahead of print]
Amtmann D, Kim J, Chung H, et al.
Comparing CESD-10, PHQ-9, and PROMIS depression instruments in individuals with multiple sclerosis.
Rehabil Psychol. 2014 Mar 24. [Epub ahead of print]
Paul L, Coote S, Crosbie J, et al.
Core outcome measures for exercise studies in people with multiple sclerosis: recommendations from a multidisciplinary consensus meeting.
Mult Scler. 2014 Mar 17. [Epub ahead of print]
Lamers I, Kelchtermans S, Baert I, et al.
Upper limb assessment in multiple sclerosis: a systematic review of outcome measures and their psychometric properties.
Arch Phys Med Rehabil. 2014 Mar 13. pii: S0003-9993(14)00185-3.[Epub ahead of print]
Senders A, Bourdette D, Hanes D, et al.
Perceived stress in multiple sclerosis: the potential role of mindfulness in health and well-being.
J Evid Based Complementary Altern Med. 2014 Feb 20. [Epub ahead of print]
Jongen PJ, Ruimschotel R, Heerings M, et al.
Improved self-efficacy in persons with relapsing remitting multiple sclerosis after an intensive social cognitive wellness program with participation of support partners: a 6-months observational study.
Health Qual Life Outcomes. 2014 Mar 19;12(1):40.
Read the full text of this paper
Benito-León J, Labiano-Fontcuberta A, Mitchell AJ, et al.
Multiple sclerosis is associated with high trait anger: a case-control study.
J Neurol Sci. 2014 Feb 26. pii: S0022-510X(14)00132-4.[Epub ahead of print]
Viner R, Patten SB, Berzins S
Prevalence and risk factors for suicidal ideation in a multiple sclerosis population.
J Psychosom Res. 2014 Apr;76(4):312-6.
Miller L, Rafferty D, Paul L, et al.
A comparison of the orthotic effect of the Odstock Dropped Foot Stimulator and the Walkaide functional electrical stimulation systems on energy cost and speed of walking in multiple sclerosis.
Disabil Rehabil Assist Technol. 2014 Mar 17. [Epub ahead of print]
Pregnancy and childbirth
Lu E, Zhu F, Zhao Y, et al.
Birth outcomes in newborns fathered by men with multiple sclerosis exposed to disease-modifying drugs.
CNS Drugs. 2014 Mar 19. [Epub ahead of print]
Hadgkiss EJ, Jelinek GA, Weiland TJ, et al.
The association of diet with quality of life, disability, and relapse rate in an international sample of people with multiple sclerosis.
Nutr Neurosci. 2014 Mar 17. [Epub ahead of print]
Quinn D, Bowen A, Leary A.
The value of the multiple sclerosis specialist nurse with respect to prevention of unnecessary emergency admission.
Mult Scler. 2014 Mar 19. [Epub ahead of print]
Koffman J, Goddard C, Silber E, et al.
Comprehending the inexplicable: qualitative accounts of black Caribbean and white British people severely affected by multiple sclerosis.
BMJ Support Palliat Care. 2014 Mar;4 Suppl 1:A20.