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Disease-modifying Therapy (disease-modifying + therapy)
Selected AbstractsTranslational experimental therapeutics: The translation of laboratory-based discovery into disease-related therapyMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2007Karl Kieburtz MD Abstract In the past decade, there has been an increasing emphasis on laboratory-based translational research. This has led to significant scientific advances in our understanding of disease mechanisms and in the development of novel approaches to therapy such as gene therapy, RNA interference, and stem cells. However, the translation of these remarkable scientific achievements into new and effective disease-modifying therapies has lagged behind these scientific accomplishments. We use the term "translational experimental therapeutics" to describe the pathway between the discovery of a basic disease mechanism or novel therapeutic approach and its translation into an effective treatment for patients with a specific disease. In this article, we review the components of this pathway, and discuss issues that might impede this process. Only by optimizing this pathway can we realize the full therapeutic potential of current scientific discoveries and translate the astounding advances that have been accomplished in the laboratory into effective treatments for our patients. Mt Sinai J Med 74: 7-14, 2007. Copyright © 2007 Mount Sinai School of Medicine [source] Defining disease-modifying therapies for PD,A road map for moving forward,MOVEMENT DISORDERS, Issue 12 2010C. Warren Olanow MD Abstract A disease-modifying therapy that slows or stops disease progression is one of the major unmet needs in the management of Parkinson's disease. To date, no therapy has been approved for disease modification despite promising laboratory data and positive results in clinical trials. This is because confounding symptomatic or pharmacologic effects cannot be excluded. The delayed start study provides an opportunity to define therapies that provide benefit that cannot be explained by an early symptomatic effect alone. However, this trial design does not necessarily provide a meaningful measure of the effect of the intervention on cumulative disability. In contrast, the long-term simple study provides a measure of the effect of the drug on cumulative disability but does not address mechanism of action. Together these two trials provide a road map for defining a disease modifying drug and determining the long term cumulative effect of the drug on the disease. © 2010 Movement Disorder Society [source] Relation between inflammation and symptoms in asthmaALLERGY, Issue 3 2009I. Tillie-Leblond Asthma symptoms are the main reason for healthcare utilization and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. A French expert group studied the association between inflammation and asthma symptoms by carrying out a critical review of the international literature. Uncontrolled asthmatics have an increased number of polynuclear eosinophils in the induced sputum and an increased production of exhaled NO. Control by anti-inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggest that there is a relationship between the perception of symptoms and eosinophilic inflammation and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow-up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference disease-modifying therapy for persistent asthma. Recent studies demonstrated that adjustment of anti-inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total number of doses of inhaled corticosteroids. [source] Defining disease-modifying therapies for PD,A road map for moving forward,MOVEMENT DISORDERS, Issue 12 2010C. Warren Olanow MD Abstract A disease-modifying therapy that slows or stops disease progression is one of the major unmet needs in the management of Parkinson's disease. To date, no therapy has been approved for disease modification despite promising laboratory data and positive results in clinical trials. This is because confounding symptomatic or pharmacologic effects cannot be excluded. The delayed start study provides an opportunity to define therapies that provide benefit that cannot be explained by an early symptomatic effect alone. However, this trial design does not necessarily provide a meaningful measure of the effect of the intervention on cumulative disability. In contrast, the long-term simple study provides a measure of the effect of the drug on cumulative disability but does not address mechanism of action. Together these two trials provide a road map for defining a disease modifying drug and determining the long term cumulative effect of the drug on the disease. © 2010 Movement Disorder Society [source] A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's diseaseMOVEMENT DISORDERS, Issue 11 2010Barry J. Snow MD Abstract Multiple lines of evidence point to mitochondrial oxidative stress as a potential pathogenic cause for Parkinson's disease (PD). MitoQ is a powerful mitochondrial antioxidant. It is absorbed orally and concentrates within mitochondria where it has been shown to protect against oxidative damage. We enrolled 128 newly diagnosed untreated patients with PD in a double-blind study of two doses of MitoQ compared with placebo to explore the hypothesis that, over 12 months, MitoQ would slow the progression of PD as measured by clinical scores, particularly the Unified Parkinson Disease Rating Scale. We showed no difference between MitoQ and placebo on any measure of PD progression. MitoQ does not slow the progression of PD, and this finding should be taken into account when considering the oxidative stress hypothesis for the pathogenesis of PD. © 2010 Movement Disorder Society [source] Natalizumab drug holiday in multiple sclerosis: Poorly ToleratedANNALS OF NEUROLOGY, Issue 3 2010Joep Killestein MD It has been suggested that natalizumab-associated progressive multifocal leukoencephalopathy may be prevented by structured interruptions of treatment. Evidence supporting such a drug holiday is not yet available. Here we present initial observations in 10 multiple sclerosis patients who were stringently monitored up to 6 months after discontinuation of the infusions. Cumulatively, a combination of clinical relapse and new and/or enhanced lesions on magnetic resonance imaging had occurred in 7 of 10 patients. Although numbers are small, our data suggest that in patients who were switched to natalizumab because of disease activity despite first-line treatment, a natalizumab drug holiday without reinstatement of alternate disease-modifying therapy is poorly tolerated. Ann Neurol 2010 [source] Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 7 2003Fiona M. McQueen Objective Magnetic resonance imaging (MRI) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis (RA), as well as bone edema and erosion. These features are visible before radiographic joint damage occurs. We sought to examine whether MRI of one body region (the wrist) can be used to predict whole-body radiography scores reflecting joint damage at 6 years. Methods We conducted a 6-year prospective study of a cohort of patients who fulfilled the criteria for RA at presentation, using clinical parameters, radiographs, and MRI scans of the dominant wrist. Of the 42 patients enrolled at baseline, full MRI, radiographic, and clinical data were available for 31 at 6-year followup. MRI scans were scored by 2 radiologists, using a validated scoring system. Radiographs of the hands and feet were graded using the modified Sharp scoring method. MRI and radiography scores obtained at baseline and 6 years were compared, and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years. Results At 6 years, the total Sharp score correlated significantly with the total MRI score and the MRI erosion score (r = 0.81, P < 0.0001 and r = 0.79, P < 0.0001, respectively). The 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores (r = 0.56, P < 0.0001 and r = 0.33, P = 0.03, respectively). MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years, but bone erosion scores progressed (P = 0.0001), consistent with radiographic deterioration. Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline (odds ratio 6.5, 95% confidence interval 2.78,18.1). Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002). Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort. A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R2 = 0.59, adjusted R2 = 0.44). Conclusion MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage, allowing disease-modifying therapy to be targeted to patients with aggressive disease. [source] | ||||||||||