Medicine In Multiple Sclerosis Research Articles

A Multicentre, Double-Blind, Randomised, Parallel-Group, Placebo-Controlled Study of Effect of Long-Term Sativex® Treatment on Cognition and Mood of Patients with Spasticity Due to Multiple Sclerosis

Objective: When Sativex ®THC:CBD cannabinoid-based oromucosal spray was first approved as a prescription medicine for multiple sclerosis (MS) spasticity, there was some concern about its possible long-term impact on cognition and mood. The objective of this study was therefore to assess the long-term impact of Sativex on cognitive function and mood in MS patients with spasticity. Methods: 121 patients were randomly assigned Sativex or placebo in a double-blind manner. Patients self-administered treatment daily for 48 weeks while maintaining anti-spasticity therapy. The primary endpoint was the difference between treatments in Paced Auditory Serial Addition Test (PASAT) score from baseline to end of treatment. Secondary measures included Beck Depression Inventory-II (BDI-II), Subject-, Physician- and Caregiver Global Impression of Change, and Columbia-Suicide Severity Rating Scale. Results: 62 patients were randomised to Sativex and 59 to placebo. There was no difference in the effect of Sativex on PASAT and BDI-II scores compared with placebo. Subject-, Physician- and Caregiver-rated improvements in spasticity with Sativex were all statistically significant. The mean daily dose of Sativex declined gradually to 6.4 sprays per day. Conclusion: Long-term treatment with Sativex was not associated with cognitive decline or significant changes in mood in this prone population sample. Sativex was efficacious and well tolerated across the study period and no new safety concerns were identified.

Personalized medicine in multiple sclerosis: hope or reality?

Personalized treatment is highly desirable in multiple sclerosis because it is an immensely heterogeneous disease. This heterogeneity is seen in both the disease course and the treatment responses. Currently, a combination of clinical features and imaging parameters in magnetic resonance imaging is used to classify active and non-active patients and treatment responders and non-responders. Although this classification works on a group level, individual patients often behave differently from the group. Therefore additional biomarkers are needed to provide better indicators for prognosis and treatment response. Basic and clinical research have discovered different promising targets. It is now essential to verify the utility and accuracy of these markers in large, prospectively sampled patient cohorts.

The elusive biomarker for personalized medicine in multiple sclerosis

There are no objective methods or tests to predict the effectiveness of specific disease-modifying drugs (DMDs) for individual patients with multiple sclerosis (MS). There are 4 interferon-β (IFNβ) products and 4 non-IFNβ DMDs available for relapsing forms of MS, with others on the way. Randomized, placebo-controlled pivotal clinical trials showed that IFNβ drugs were only partially effective, reducing relapse rate by about 33%.1 While relapses or new MRI lesions are commonly observed in patients with MS on …

Retinoid X receptors as a potential avenue for regenerative medicine in multiple sclerosis

Multiple sclerosis (MS) is a neurodegenerative disease of the CNS in which myelin sheaths generated by oligodendrocytes are destroyed through recurrent inflammation [1]. The continuous destruction of myelin sheaths is associated with progressive degeneration of central axons, resulting in clinical decline. MS is the most common neurological disorder among young adults, and is thought to affect more than 2 million individuals worldwide. Current treatment strategies mainly aim to suppress inflammation by using immunomodulatory drugs. This is effective for the treatment of MS during the acute stages of the disease (i.e., relapse–remitting), but is largely ineffective in the chronic stages (i.e., secondary progressive), where inflammation has mostly subsided but clinical decline continues. Several lines of evidence suggest that restoring myelin to demyelinated axons will provide an effective means of preventing their loss, and so a major goal in MS research is to identify strategies to repair CNS demyelination through regenerative therapy [2]. This could involve either transplantation of stem or myelinating cells into the CNS of patients with MS, or pharmacological stimulation of myelin regeneration (remyelination) by endogenous stem and precursor cells. Regenerative therapy in MS would restore conduction and function and prevent further deterioration of axons, thus possibly bring disease progression to a halt. Although cell transplantation has been shown to be effective in animal models of myelin diseases, it is not well suited to being a treatment for MS. The multifocal nature of the disease presents obvious difficulties for direct, ‘plaque-guided’ delivery of myelinating cells, while systemic delivery of myelinating cells makes little direct contribution to repair (although it does provide potent disease-suppressing immunomodulation). In many ways, a more attractive strategy is to take a drugbased approach aimed at enhancing remyelination by promoting oligodendrocyte differentiation of endogenous CNS stem cells. Several potential drug targets for remyelination therapy have emerged in recent years and include LINGO-1, Notch1 and Wnt – all of which are negative regulators of CNS remyelination [3]. We have recently identified a positive regulator of remyelination called retinoid X receptor g (Rxrg) by microarray profiling of differentially expressed genes from rodent CNS remyelination [4]. Rxrg is a member of the RXR family of nuclear receptors that also includes Rxra and Rxrb. All three RXR members are differentially expressed in remyelination, with Rxrg displaying the greatest differential expression. We found that Rxrg is highly expressed in oligodendrocyte lineage cells during remyelination, and that inhibition of RXR activity impaired oligodendrocyte

Regenerative medicine in multiple sclerosis: Identifying pharmacological targets of adult neural stem cell differentiation

Progressive axonal loss from chronic demyelination in multiple sclerosis (MS) is the key contributor to clinical decline. Failure to regenerate myelin by adult oligodendrocyte precursor cells (OPCs), a widely distributed neural stem cell population in the adult brain, is one of the major causes of axonal degeneration. In order to develop successful therapies to protect the integrity of axons in MS, it is important to identify and understand the key molecular pathways involved in myelin regeneration (remyelination) by adult OPCs. This review highlights recent findings on the critical signaling pathways associated with OPC differentiation following CNS demyelination. We discuss the role of LINGO-1, Notch, Wnt, and retinoid X receptor (RXR) signaling, and how they might be useful pharmacological targets to overcoming remyelination failure in MS.

Complementary and alternative medicine in multiple sclerosis

Complementary and alternative medicine (CAM) is often used by patients with multiple sclerosis (MS) but has been disregarded in research until lately. Various confounding factors on CAM utilisation exist, though have hardly been investigated. Besides socio-demographic variables like education, income, gender and age, illness-related factors like severity of disease are discussed. Furthermore, the important role of psychological factors on CAM utilisation is described. In particular, coping strategies such as "rumination", "search for information" and "search for meaning in religion" are more often reported by CAM users than non-users and have important impact on CAM utilisation.

Translation towards personalized medicine in Multiple Sclerosis

In recent years the realization that the concept ‘one drug fits all’ — does not work, created the need to shift gears from ‘treating the disease’ to ‘treating the patient’, and implementation of ‘Personalized Medicine’ where treatment is tailored to the individual. In chronic and progressive diseases, such as Multiple Sclerosis (MS), the need for tailored therapeutics is especially imperative, as the consequences of an ineffective medication might be irreversible dysfunction. In recent years accumulating evidence indicates that MS is not a single disease and that patients with different disease subtypes respond differently to a medication. Environment and genetics are among the factors that determine disease subtype and activity, and the patient's response to medication. Additional factors include demographic characteristics such as gender and age, as well as chrono-biological indicators. During the last few years, advances and availability of new technologies have brought genome-wide gene expression profiling studies to many medical fields, including MS. Genomic technologies have also stimulated pharmacogenetics studies, that aim to identify genetic factors that affect response to treatment. However, pharmacogenetics information is still immature to allow its translation to clinical practice in MS. Notably, one of the major limitations in obtaining reproducible data across MS pharmacogenetics studies has been the lack of a consensus as to the appropriate method for determining clinical response. In light of the rapid advances in technology and progress in applying individualized treatment strategies in other diseases, ‘Personalized Medicine’ for MS seems feasible within the coming years.

A Randomized Pilot Study of Naturopathic Medicine in Multiple Sclerosis

Complementary and alternative medicine (CAM) use is high in people with multiple sclerosis (MS), yet there are limited reports on safety and effectiveness of CAM in MS. Naturopathic medicine encompasses a broad range of CAM modalities and may improve quality of life in patients with MS. To assess quality of life in MS subjects who received interventions designed to "model" the "whole practice" of naturopathy. A pilot, randomized, controlled study with a 6-month intervention period. Participants who met criteria for clinically definite MS. The 3 intervention arms were usual care, naturopathic medicine plus usual care, and MS education plus usual care. The primary outcome measure was quality of life (36-item short form health survey [SF-36]). Secondary outcome measures included fatigue (Modified Fatigue Impact Scale); depression (Beck Depression Inventory); cognition battery (Stroop test and Paced Auditory Serial Addition Test 3), and neurologic impairment (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite). Adverse event reporting and laboratory measures were used to assess safety. Forty-five (45) participants (15 per group) were randomized and all completed the 6-month intervention. There were no significant differences between groups on any outcome measure. There was a trend in favoring the naturopathic group in the General Health subscale of the SF-36 (p = 0.11), Timed Walk (p = 0.11), and neurologic impairment (EDSS) (p = 0.07). There was a trend favoring the Education group in the Stroop attention test (p = 0.07). There was no difference between groups in adverse events or laboratory changes. Naturopathic medicine combined with usual care for MS showed a trend in improvement in the General Health subscale of the SF-36, Timed Walk, and neurologic impairment. Evaluation of naturopathic medicine, as a multimodality regimen, warrants further investigation.

Complementary and Alternative Medicine in Multiple Sclerosis

Complementary and Alternative Medicine in Multiple Sclerosis

Complementary and Alternative Medicine in Multiple Sclerosis: Survey of Licensed Naturopaths

Objective: This paper describes the treatments and treatment outcome measures used by licensed naturopathic physicians in the United States who treat people with multiple sclerosis (MS). Design: A cross-sectional mail survey was used. Subjects: The participants were licensed naturopaths who were members of the American Association of Naturopathic Physicians. Outcome Measures: Outcome measures included practitioner demographics; patient demographics by practitioner report; recommended therapies; perceived effectiveness of treatments for MS; methods for measuring treatment effectiveness. Results: Forty three percent (43%) of the respondents (166/385) had treated at least one patient with MS while 56.9% (291/385) had never treated MS. 63.3% had treated 1–10 patients with MS, 19.9% had treated 11–20 patients with MS, and 16.8% had treated ≥20 patients with MS. Among the naturopaths, 68.1% communicated with an M.D. about their patient(s)' care and the majority of patients with MS were diagnosed by an M.D. (mean % = 96.3). The mean number of therapies recommended for M.S. was 3.91 (standard deviation [SD] =2.01, range 1–10). The most frequently recommended therapies included, diet (52.4%), essential fatty acid supplementation (44.6%), vitamin/mineral supplementation (33.7%), homeopathy (30.7%), botanicals (22.3%), and antioxidants (18.1%). Respondents perceived their treatments as "very effective" for the following stages of MS: early stage (57.2%); middle stage (25.3%); and late stage (3.0%). Respondents perceived their treatments as "very effective" for the following disease-related outcomes: improved quality of life (59.0%); decrease relapse rates (48.2%); decreased symptom severity (45.8%); prevention of disease progression (41.6%). The methods used "most often" for measuring treatment effectiveness included, patient report (88.0%); physical examination (27.1%); medical records/laboratory testing (13.3%). The mean estimated percentage of patients not taking conventional disease-modifying medication was 51.2% (SD = 42.7%). Conclusions: Naturopaths use both a broad range and multiple complementary and alternative medicine CAM therapies for treating MS and report treatment effectiveness on the following outcomes: quality of life; symptom severity; relapse rates; and disease progression. Further research on single CAM therapies and holistic CAM systems is warranted in MS.

Complementary and Alternative Medicine in Multiple Sclerosis: Survey of Licensed Naturopaths

This paper describes the treatments and treatment outcome measures used by licensed naturopathic physicians in the United States who treat people with multiple sclerosis (MS). A cross-sectional mail survey was used. The participants were licensed naturopaths who were members of the American Association of Naturopathic Physicians. Outcome measures included practitioner demographics; patient demographics by practitioner report; recommended therapies; perceived effectiveness of treatments for MS; methods for measuring treatment effectiveness. Forty three percent (43%) of the respondents (166/385) had treated at least one patient with MS while 56.9% (291/385) had never treated MS. 63.3% had treated 1-10 patients with MS, 19.9% had treated 11-20 patients with MS, and 16.8% had treated > or =20 patients with MS. Among the naturopaths, 68.1% communicated with an M.D. about their patient(s)' care and the majority of patients with MS were diagnosed by an M.D. (mean % = 96.3). The mean number of therapies recommended for M.S. was 3.91 (standard deviation [SD] =2.01, range 1-10). The most frequently recommended therapies included, diet (52.4%), essential fatty acid supplementation (44.6%), vitamin/mineral supplementation (33.7%), homeopathy (30.7%), botanicals (22.3%), and antioxidants (18.1%). Respondents perceived their treatments as "very effective" for the following stages of MS: early stage (57.2%); middle stage (25.3%); and late stage (3.0%). Respondents perceived their treatments as "very effective" for the following disease-related outcomes: improved quality of life (59.0%); decrease relapse rates (48.2%); decreased symptom severity (45.8%); prevention of disease progression (41.6%). The methods used "most often" for measuring treatment effectiveness included, patient report (88.0%); physical examination (27.1%); medical records/laboratory testing (13.3%). The mean estimated percentage of patients not taking conventional disease-modifying medication was 51.2% (SD = 42.7%). Naturopaths use both a broad range and multiple complementary and alternative medicine CAM therapies for treating MS and report treatment effectiveness on the following outcomes: quality of life; symptom severity; relapse rates; and disease progression. Further research on single CAM therapies and holistic CAM systems is warranted in MS.

Pharmacogenetic Development of Personalized Medicine: Multiple Sclerosis Treatment as a Model.

The goal of pharmacogenetics is to identify "genetic fingerprints" that may predict a patient's response to pharmaceutical treatment. The use of pharmacogenetics replaces the trial-and-error strategy, which governs much of our clinical decision-making regarding treatment allocation in current medical practice, with individually tailored therapy. We review a pharmacogenetic research model, which implements high-throughput single nucleotide polymorphism technology to establish the correlation between drug-responsiveness and genetic polymorphisms of Copaxone(R)-treated multiple sclerosis patients. Implementation of similar pharmacogenetic approaches may promote the development of personalized medicine in multiple sclerosis as well as in other diseases. (c) 2002 Prous Science. All rights reserved.