Lancet neurology
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The use of interferon beta and glatiramer acetate for the treatment of multiple sclerosis (MS) has, to some extent, changed the course of the disease. The annual relapse rate of patients treated with these drugs is lower than that in placebo-treated patients, and more treated patients remain relapse-free compared with untreated patients. In addition, these compounds reduce the development of new lesions, as detected by MRI. ⋯ The limited effectiveness of approved treatments for MS, as well as reports of adverse events and toxicity, emphasise the need for the development of new therapies with improved efficacy and fewer side-effects. Clinical observations, increased understanding of the underlying pathophysiology of the disease, and advances in biotechnology have led to several new therapeutic approaches to the treatment of MS that are currently under investigation. WHERE NEXT? Mitoxantrone has recently been shown to produce benefit when used to treat patients with progressive MS; it may also be an effective second-line treatment for patients who do not respond to interferon beta or glatiramer acetate. Over the past few years, several studies have drawn attention to the potential of natalizumab, alemtuzumab, statins, and oestrogens as effective treatments for MS. These drugs are at different stages of clinical development and additional clinical data are needed to support their use and devise dosage regimens. However, they are important and attractive candidates for several reasons: they counteract a fundamental and well-defined pathophysiological process; they have a less cumbersome route of administration than interferon beta and glatiramer acetate; or they have a remarkable safety record.
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Recent epidemiological and experimental studies have renewed interest in the hypothesis that the environment has a role in the pathogenesis of Parkinson's disease (PD). Epidemiological studies have identified protective associations (eg, smoking) as well as adverse risk factors (eg, pesticide exposure) for PD. ⋯ Toxins interact, in vitro and in vivo, with alpha-synuclein, an endogenous protein that is implicated in pathology of PD. Similarities between clinical and experimental findings, such as the role of pesticide exposure as a potential environmental risk factor, highlight the importance of a multidisciplinary approach to the aetiology of PD.
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Although secondary end-organ damage in diabetes has generally been thought to result from long-term passive shunting of excess glucose through alternative metabolic pathways, recent studies have elucidated a second mechanism of pathogenesis that involves active changes in gene expression in neurons of the CNS. These changes in gene expression result in molecular and functional changes that can become maladaptive over time. In this review, we examine two neuronal populations in the brain that have been studied in human beings and animal models of diabetes. ⋯ And second, we describe how changes in hippocampal synaptic plasticity can lead to cognitive and behavioural deficits in chronic diabetes. Changes in neuronal gene expression in diabetes represent a new pathway for diabetic pathogenesis. This pathway may hold clues for the development of therapies that, via the targeting of neurons, can slow or prevent the development of diabetic end-organ damage.