Doktorarbeit / Dissertation, 2017
59 Seiten, Note: PG MEDICAL DOCTOR & CEO
1. Dissertation Methodology
2. Aims and Objectives
3. Introduction
4. Major Neuro-protective Methods
4.1 Literature Review on Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis
4.1.1 Introduction
4.1.2 Material and Methods
4.1.3 Randomization and Criteria
4.1.4 Figures
4.1.5 Results
4.2 Literature Review on Clinical trial with ceftriaxone in amyotrophic lateral sclerosis
4.2.1 Introduction
4.2.2 Material and Methods
4.2.3 Randomization and Criteria
4.2.4 Figures
4.2.5 Results
4.3 Literature Review on Randomised, Double-Blind, Placebo-Controlled, Study of Safety and Efficacy of Dexpramipexole in Subjects with ALS
4.3.1 Introduction
4.3.2 Material and Methods
4.3.3 Randomization and Criteria
4.3.4 Figures
4.3.5 Results
4.4 Literature Review on Efficacy and Safety of MCI-186 Edaravone
4.4.1 Introduction
4.4.2 Material and Methods
4.4.3 Randomization and Criteria
4.4.4 Figures
4.4.5 Results
5. Major Neuro-stimulative Methods
5.1 Literature Review on CY4031-VITALITY-ALS (TIRASEMTIV)
5.1.1 Introduction
5.1.2 Material and Methods
5.1.3 Randomization and Criteria
5.1.4 Figures
5.1.5 Results
5.2 Literature Review on Multi-Centre, Randomised Controlled Study of NeuRx® Diaphragm Pacing System™ In Participants with A LS
5.2.1 Introduction
5.2.2 Material and Methods
5.2.3 Randomization and Criteria
5.2.4 Figures
5.2.5 Results
5.3 Literature Review on Repetitive Transcranial Magnetic Stimulation (rTMS) in ALS
5.3.1 Introduction
5.3.2 Material and Methods
5.3.3 Randomization and Criteria
5.3.4 Figures
5.3.5 Results
6. Critical Analysis
7. Conclusions and Future Scopes
7.1 Conclusions
7.2 Future Scope
This dissertation aims to conduct a comparative analysis of major therapeutic options for Amyotrophic Lateral Sclerosis (ALS), categorized into Neuroprotective Methods (NPMs) and Neurostimulating Methods (NSMs). By evaluating clinical trials and existing literature, the work seeks to determine the efficacy of these interventions, both as singular treatments and in combination, to provide a more structured approach to ALS management through a proposed "TOS-ALS" classification system.
2.1. Literature Review on Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis
Glutamate, which do form in CNS as being a variant of transport form of glutamine or stimulant glutaminergic electrical tract.
These highly charged chemical bodies lead to early and accelerated nerve cell apoptosis via accumulation through calcium dependent gated paths.
Hence any formulation capable of interfering the above system can be of some use in terms of ALS therapy or relief or any intervention.
This made Riluzole, ie 2-amino-6-(trifluoromethoxy) benzothiazole or, RP 54274; eligible to get checked by a clinical trial under GMP European guidance, in a progressive, bias free, randomised and placebo controlled manner. The attempt hence done years back is known as “controlled trial of Riluzole in ALS”.
The RP 54274 has already shown the ability of leak proofing the glutamic acid release in proximal nervous convex synapses, and hamper the distal, synaptic post ‘fluid-zone-vesicular’ propagation of excitatory amino acid (EAA).
Chapter 1: GENERAL INTRODUCTION: This chapter outlines the methodology of the dissertation and introduces the current understanding of ALS, including its classification and existing management challenges.
Chapter 2: MAJOR NEURO-PROTECTIVE METHODS: This chapter provides a detailed literature review and evaluation of four key neuroprotective drugs—Riluzole, Ceftriaxone, Dexpramipexole, and Edaravone—focusing on their trial results.
Chapter 3: MAJOR NEURO-STIMULATIVE METHODS: This chapter investigates stimulation-based therapies, covering Tirasemtiv, the Diaphragm Pacing System, and Repetitive Transcranial Magnetic Stimulation.
Chapter 4: CRITICAL ANALYSIS: This section offers a comprehensive synthesis of all discussed trials, analyzing their results, limitations, and overall impact on ALS management.
Chapter 5: CONCLUSIONS and FUTURE SCOPES: The final chapter summarizes the dissertation's findings, proposes the TOS-ALS classification system, and highlights emerging therapeutic avenues for future research.
Amyotrophic Lateral Sclerosis, ALS, Neuroprotection, Neurostimulation, Riluzole, Edaravone, Clinical Trials, TOS-ALS, Survival Analysis, Glutamate, Respiratory Function, Tirasemtiv, Diaphragm Pacing System, rTMS, Disease Progression
The work focuses on comparing various therapeutic management options for Amyotrophic Lateral Sclerosis, specifically categorizing them into neuroprotective and neurostimulating approaches.
The central themes include the evaluation of pharmacological interventions, the role of stimulation technologies in respiratory and muscular support, and the proposal of a new binary management classification system.
The primary aim is to evaluate major therapeutic options for ALS in a comparative manner, assessing their effectiveness in improving survival, quality of life, and symptomatic relief.
The author utilizes a systematic literature review and critical analysis approach, examining data from multiple randomized, double-blind, placebo-controlled clinical trials to synthesize evidence on current ALS treatments.
The main body evaluates individual drugs (such as Riluzole and Edaravone) and therapies (like Diaphragm Pacing and rTMS), providing details on their study design, randomization, inclusion/exclusion criteria, and results.
Key terms include ALS, Neuroprotection, Neurostimulation, Riluzole, Edaravone, clinical trial efficacy, disease progression, and the proposed TOS-ALS classification.
TOS-ALS stands for "Therapy Options Classification system for ALS," which is a binary classification system proposed by the author to streamline the selection of neuroprotective and neurostimulating treatments.
The dissertation analyzes DPS as a neurostimulating intervention, noting its use on humanitarian grounds despite mixed trial results regarding its impact on overall survival.
It acts as the "cream" of the research, where the author synthesizes trial outcomes to determine which interventions show potential for modifying future standard-of-care guidelines.
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