14 de mayo de 2004
Londres
Jano On-line
01/04/2003
Investigadores del Barrow Neurological Institute de Phoenix (Estados Unidos) han presentado un trabajo en la Reunión Anual de la Academia Americana de Neurología, que se desarrolla en Honolulu (Hawai), mostrando que la simvastatina, fármaco indicado para reducir los niveles de colesterol, constituye una terapia prometedora para la forma más frecuente de esclerosis múltiple, la llamada remitente-recidivante.
Investigaciones anteriores habían sugerido que las estatinas podían tener valor terapéutico para reducir las lesiones inflamatorias del sistema nervioso central (SNC), como las que se dan en la esclerosis múltiple. Los autores estaban interesados en evaluar la efectividad y seguridad de este fármaco como tratamiento de la enfermedad neurológico, monitorizando el número y volumen de lesiones del SNC mediante resonancia magnética.
El
análisis con esta técnica de imagen antes y
después del tratamiento reveló una significativa
reducción tanto de la cantidad como del volumen de lesiones
activas entre los pacientes que recibieron simvastatina. Por otra
parte, no se registraron efectos adversos de relevancia entre los
pacientes tratados.
Noticias Relacionadas
| |
Las estatinas podrían ser útiles como tratamiento de la esclerosis múltiple 07/11/2002 |
| |
Varias estatinas muestran in vitro ejercer un efecto protector frente a la esclerosis múltiple 08/10/2002 |
| |
Las estatinas podrían ser útiles en el tratamiento de la esclerosis múltiple 23/04/2002 |
© Ediciones
Doyma S.L.
An Open-Label, Single Arm Study of
Simvastatin as a Therapy for Multiple Sclerosis (MS)
Timothy Vollmer, Phoenix, AZ, Valerie Durkalski, William Tyor, Charleston, SC, John Corboy, Denver, CO, Jana Preiningerova, Silva Markovic-Plese, Marco Rizzo, New Haven, CT, Lyndon Key, Inderjit Singh, Charleston, SC
Objective:
To assess the safety and efficacy by MRI of oral treatment with simvastatin at one daily dose(80mg q.d.) in relapsing-remitting (RR) MS patients.
Background:
Studies in the murine EAE model indicate that members of the statin class of drugs e.g.,simvastatin, can inhibit CD4+ TH-1 T cell function,enhance CD4+ TH-2 T cell activity,and inhibit the increased expression of iNOS and TNF-alpha in CNS inflammatory lesions. These studies indicate that statins may have a therapeutic value for the treatment of MS.
Design/Methods:
Three centers participated in an open-label,single-arm trial. Subjects age 18-55 years who were clinically diagnosed with RR-MS were invited to participate. Subjects underwent a pre-treatment period of three months. Subjects that had at least one Gd-enhanced lesion were eligible for six months of treatment with simvastatin. During the study period, neurological assessments and blood values were collected as well as additional brain MRIs. The primary outcome for efficacy was the difference in the mean number of Gd-enhancing lesions obtained from three monthly cranial MRIs performed during pre-treatment and from three performed at Months 4,5 and 6 of treatment. A blinded central reader evaluated MRI films. Secondary outcomes included safety data,MRI measures(i.e.,volumes of Gd-lesions and lesions,number of new Gd-lesions),change from baseline in neurological assessments, and cytokine activity. The study was approved by the Institutional Review Board at each participating center.
Results:
Forty-five subjects (33 female/12 male) were enrolled into the pre-treatment phase of the study. Baseline median values included: age of 45,EDSS of 3.0,MSFC z-score of 0.133, and duration of disease of five years. Thirty subjects were enrolled into the treatment phase. Three did not complete the study (2 withdrew consent;1 lost to followup). Of the treated subjects,the annualized rates of clinically significant relapses during pre- and post-treatment were 0.43 and 0.32,respectively. Preliminary analysis of pre- and post-treatment MRI data for treated subjects indicated a decrease in the mean number of Gd-lesions (p=0.0001) and in the mean volume of Gd-lesions (p=0.0016). The pre-treatment means(sd) for number and volume of Gd-lesions were 2.35(1.94) and 237.96(337.44),respectively. Post-treatment means were 1.31(1.30) and 141.52(292.42),respectively. Safety data showed no serious adverse events related to the study drug. Final quality assurance checks and analyses are currently being conducted.
Conclusions:
Preliminary data suggest that daily treatment with 80mg of simvastatin may be safe and effective for the treatment of RR-MS. Randomized-controlled studies will need to be conducted to definitively ascertain the effectiveness of this treatment.
Supported By:
An unrestricted educational grant from Merck, Inc.
Category - MS and Related Diseases
SubCategory -
Clinical
Trials
Fuente: American
Academy of Neurology (AAN)
55th Annual Meeting
Speakers' Abstracts about Multiple Sclerosis
http://www.aan.com/professionals/
April
1, 2003
Summary:
A small clinical trial was done of the oral
cholesterol-lowering drug Zocor® in 30 individuals with
relapsing-remitting MS:
Details:
A
small, pilot study found that the cholesterol-lowering pill
Zocor® (simvastatin, Merck & Co., Inc.) safely
reduced the number of new lesions in 30 people with relapsing-remitting
multiple sclerosis. Dr. Timothy Vollmer (formerly of Yale University
and now at Barrow Neurological Institute, Phoenix) and colleagues reported their results
at the 2003 Annual Meeting of the American Academy of Neurology.
Larger, controlled studies will need to be conducted to ascertain the
effectiveness of Zocor for MS.
Background: Previous studies have
suggested that cholesterol-lowering “statins” can alter immune
responses in a way that may hold promise in treating multiple
sclerosis. Dr. Oliver Neuhaus
(Karl-Franzens-Universitat, Graz, Austria) and colleagues reported that
in cells taken from individuals with MS, several forms of statins –
including mevastatin, simvastatin (Zocor®) and lovastatin
(Mevacor®)
– were capable of inhibiting several different immune responses and
markers of inflammation typically involved in MS (Neurology, October 8, 2002).
Simvastatin was the most potent, followed by lovastatin and mevastatin.
However, in those studies, statins stimulated the release of some
messenger proteins known to increase inflammation as well, making their
ultimate value in treating MS uncertain. . Additional
studies on statins have been published, including one by Drs. Scott
Zamvil (University of California, San Francisco) and Sawsan Youssef (Stanford University) and
colleagues. They reported in the November 7, 2002 issue of Nature that Lipitor (atorvastatin, Pfizer, Inc.) prevented or
reversed the MS-like disease EAE in mice. The mechanism underlying the
drug’s ability to treat EAE appears to be immune system modulation, not
a cholesterol-lowering mechanism.
These promising
results
in laboratory studies provide some information about biological
mechanisms of statins. Meanwhile, results are now being reported from a
small, early study of Zocor in people with relapsing-remitting MS.
Study: Three centers (Yale
University, New Haven, CT; Medical College of South Carolina,
Charleston; University of Colorado at Denver) participated in this
first human study of a statin in MS. Forty-five subjects were enrolled,
undergoing MRI (magnetic resonance imaging) scans monthly for three
months. Those that had at least one new lesion were then eligible for
six months of treatment with 80 mg. of Zocor daily. During the study
period, participants underwent neurological assessments and MRI scans,
and blood samples were also taken. The primary outcome that
investigators looked at was the difference in the mean number of new
lesions between scans taken during pre-treatment, and during months 4,
5 and 6 of the treatment period. Secondary outcomes were drug safety,
other MRI results, and changes in neurological assessments and immune
system activity. This was an “open-label” study, meaning that all
patients received Zocor, and the effects of this treatment were not
compared with those of an inactive placebo.
Results: Preliminary analysis
of the results indicates a significant (43%) decrease in the mean
number of new lesions, and in the volume of new lesions. No serious
adverse events related to treatment occurred. Analysis of immune
responses suggested a positive shift away from inflammation, but there
were no differences observed in neurological status or disability in
this short study.
Conclusions: This small study,
indicating possible benefit on lesion development and immune activity,
shows promising results for Zocor in treating people with
relapsing-remitting MS. However, the safety and effectiveness of this
treatment must be ascertained in larger, controlled trials. Such
studies of this and other statins are now in the planning stages.
Individuals concerned about the role of statins in MS should discuss
the results of this study with their personal physicians.
-- Research
Programs
Department
Fuente: http://www.nationalmssociety.org/Research-2003Apr1.asp
From:
http://www.medscape.com/viewarticle/467256
January 26, 2004
Medscape
In a small study presented at the American Academy of Neurology in April 2003 by Timothy Vollmer, MD, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center (Phoenix, Arizona), and colleagues,[7] daily treatment with oral simvastatin (Zocor; Merck Inc., Whitehouse Station, New Jersey) reduced the number and volume of magnetic resonance imaging (MRI)-detected central nervous system (CNS) lesions in patients with relapsing-remitting multiple sclerosis (RR-MS). MS lesions are classified as areas of inflammation and are markers for disease progression and severity. This study was undertaken to test the hypothesis that the anti-inflammatory properties of statins would slow the progression of the disease and, in turn, reduce its severity.
Dr. Vollmer and colleagues examined the safety and efficacy of once-daily simvastatin (80 mg) for 6 months in 27 patients (age range, 18-55 years) with RR-MS who had at least 1 lesion on pretreatment MRI. All patients who participated in the open-label, single-arm study underwent cranial MRIs each month for 3 months before and after treatment.
A comparison of MRI findings during the pretreatment phase of the study revealed that the use of statin therapy was associated with a reduction in the mean number (2.35 vs 1.31, respectively; P = .0001) and volume (237.96 vs 141.52, respectively; P = .0016) of lesions. In addition, patients had fewer clinically significant relapses during posttreatment than during pretreatment (0.32 vs 0.43, respectively), and no serious adverse events with simvastatin use were reported by study participants.
Although treatment with simvastatin (80
mg/day) shows promise for patients with RR-MS, the investigators
emphasized that randomized controlled studies are needed to
definitively confirm its efficacy.
Copyright © 2004, Medscape
Londres