Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial

Chataway, Jeremy; Schuerer, Nadine; Alsanousi, A; Chan, Dennis; MacManus, David; Hunter, K; Anderson, Valerie; Bangham, Charles R. M.; Clegg, Shona; Nielsen, Casper; Fox, Nick C.; Wilkie, David; Nicholas, Jennifer M.; Calder, Virginia L.; Greenwood, John; Frost, Chris; Nicholas, Richard

doi:10.1016/s0140-6736(13)62242-4

Cited by 371 publications

(334 citation statements)

References 51 publications

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“…Cholesterol is also required for important brain functions, including myelin formation, immune functioning, neuronal signaling, and vascular function; therefore, changes may reflect not only treatment effects, but also pathophysiological effects. Interestingly, the MS-STAT study of the cholesterol-lowering drug, simvastatin, reported reduction of brain atrophy in secondary progressive MS (32). This may suggest that reductions in cholesterol may affect accumulation of atrophy in MS.…”

Section: Discussionmentioning

confidence: 99%

Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients

Uher

Fellows

Horáková

et al. 2017

Journal of Lipid Research

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Interferon- (IFN-) treatment is one of the most widely used disease-modifying treatments for multiple sclerosis (MS). The efficacy of recombinant human IFN- for relapsing MS has been established by multiple double-blind placebo-controlled multi-center trials (1-3). IFN- can delay the conversion to clinically definite MS (CDMS) in patients with a first demyelinating event (4-6), which supports early intervention with IFN-.MRI atrophy measures of brain volume and gray matter, white matter, and lateral ventricle volumes provide quantitative measures of global and tissue-specific brain volumes (7-9). Brain atrophy is useful for evaluating disease progression and therapeutic efficacy in MS (7) because it is a predictor of physical disability, cognitive dysfunction, and quality of life (10). However, there is a lack of effective serum biomarkers capable of predicting atrophy in MS patients.There is considerable inter-individual variability of IFN1a effectiveness among MS patients. Phase III studies of IFN- indicate a 30-40% general clinical benefit, although the response varies significantly among MS patients. On MRI, approximately 40% of patients show complete suppression of new contrast-enhancing lesions (CELs), whereas 20% of patients have less than 70% suppression

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Section: Discussionmentioning

confidence: 99%

Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients

Uher

Fellows

Horáková

et al. 2017

Journal of Lipid Research

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“…Recently, encouraging results with treatment with statins in individuals with secondary progressive MS were reported by Chataway and colleagues, where brain atrophy was slowed when statins were given compared with placebo (77).…”

Section: Translational Research At Stanford Over the Past 20 Yearsmentioning

confidence: 99%

A Journey in Science: The Privilege of Exploring the Brain and the Immune System

Steinman

2016

Mol Med

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Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the Cerami Award Monograph is by Lawrence Steinman, MD, of Stanford University in California. A visionary in the field of neurology, this is the story of Dr. Steinman's scientific journey.

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“…10 One such parameter is MRI atrophy, for example in the MS-STAT trial (NCT00647348, ClinicalTrials.gov) -using high-dose simvastatin as a neuroprotective agent, the reduction in annualised brain atrophy rate versus placebo was about 40%. 36 This technique and others, such as optical coherence tomography (OCT) and spinal cord atrophy, are starting to be harnessed in more modern trial platforms, eg the phase II multiple sclerosis secondary-progressive multi-arm randomisation trial (MS-SMART; NCT01910259, ClinicalTrials.gov) where three putative neuroprotective agents (amiloride, fluoxetine and riluzole) are being compared with placebo. 37 ClinicalTrials.gov).…”

Section: Cis Treatmentmentioning

confidence: 99%

Multiple sclerosis, a treatable disease

Doshi

Chataway

2017

Clinical Medicine

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This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic impacts. As MS can affect any part of the central nervous system, the presentation is often diverse; however, there are key features that can be useful in the clinic. We comment on the diagnostic criteria and review the main subtypes of MS, including clinically isolated syndrome, relapsing remitting MS, secondary progressive MS and primary progressive MS. Although the underlying aetiology of MS is still not known, we summarise those with most evidence of association. Finally, we aim to present treatment strategies for managing the acute relapse, disease-modifying therapies and MS symptoms. This review highlights that progressive MS is an area where there is currently a paucity of available diseasemodifying treatments and this will be a major focus for future development.KEYWORDS : Diagnostic criteria , epidemiology , multiple sclerosis , progressive multiple sclerosis , treatments What is multiple sclerosis?Multiple sclerosis (MS) is an acquired disabling neurological disease of young adults, affecting approximately 2.3 million people worldwide. It is most prevalent in North America (140 cases per 100,000) and Europe (108 cases per 100,000); the prevalence is lowest in sub-Saharan Africa (2.1 cases per 100,000) and East Asia (2.2 cases per 100,000).1 Overall, there are approximately 120,000 people with MS in the UK. 2MS is an inflammatory disease of the central nervous system (CNS), which causes a heterogeneous array of symptoms and signs because of differential involvement of motor, sensory, visual and autonomic systems. Optic neuritis (inflammation of the optic nerve), Uhthoff's phenomenon (transient fluctuation or worsening of MS symptoms with a rise in body temperature) and Lhermitte's phenomenon (an abnormal electric-shock like sensation down the spine or limbs on neck flexion) are characteristic of MS.3-5 MS relapses occur because of focal areas ABSTRACTMultiple sclerosis, a treatable disease of demyelination evolving over 24 hours and persisting for days or weeks before generally, though not exclusively, improving.4,6

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Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial

Cited by 371 publications

References 51 publications

Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients

Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients

A Journey in Science: The Privilege of Exploring the Brain and the Immune System

Multiple sclerosis, a treatable disease

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