ALS, an incurable fatal syndrome (than being just a misnomer of disease), affecting each organ system and life (quality and quantity), through glutamate induced free radical and electrical injuries to nerves. This giant needs to be further dig into, with deeper investigations for newer management options and betterment of previous treatments, aiming a comparison of various strategies, to invent most sustainable and suitable choice for PALS.
Broadly ALS can be classified as sporadic and familial, based on aetiology. There are various subtypes in each of them with regard to the genetic, pathological and nucleic acid mutational conflicts. Like in a case of “Diabetes Mellitus”, we don’t haphazardly enlist all drugs and precautions, instead first classify them into pharmaco-therapeutic or lifestyle changes, similarly for ALS, I’ve proposed for a new management classification system for clinical purposes after feeling a need of such, near the end of dissertation. Only approved and unavoidable option in present scenario is glutamic acid release inhibitor
“Riluzole” and the basic or standard life care for the disease. Broad spectrum antibiotic “Ceftriaxone” has been found to cross the blood brain barrier and increase GLT-1 channel, leading to fall in glutamate levels of nervous system and hence can be an add-on option to benefit more. RPPX: Dexpramipexole; recently developed drug especially for SOD-1 and TDP-43 mutation ALS, showed mitochondrial protection and reciprocated it as improved ALSFRS. Though the medication can be a future option, but for now trials have failed to reflect major benefit on a 12-month follow up.
MCI186: Edaravone, by virtue of being antioxidant in character (supposedly); has gained FDA approval in 2017 due to promising results. Drug has been in use in USA since May 2017 and will be introduced in European market following political, copyright and legal decisions in time. Tirasemtiv activates muscle troponin complex leading to increased sensitivity of neuromuscular junction (NMJ) for calcium (Ca2+) and hence help to overcome the fatigue of ALS. Study is yet undergoing with biggest hope amongst all newer options. DPS using local electrodes in diaphragm, overcome respiratory efforts in ALS affected patients. Being an “HDE” due to dramatic symptomatic relief, it’s being considered in guidelines, even after multiple failed trial results on 12 month follow up and absolutely no effect on survival and disease progression.
Table of Contents
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
Research Goals and Themes
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.
- Comparative evaluation of neuroprotective drugs, including Riluzole, Ceftriaxone, Dexpramipexole, and Edaravone.
- Assessment of neurostimulating interventions, specifically Tirasemtiv, Diaphragm Pacing Systems (DPS), and Transcranial Magnetic Stimulation (rTMS).
- Development of the "Therapy Options Classification system for ALS" (TOS-ALS) to improve clinical management.
- Analysis of survival rates, functional status, and quality of life (QOL) outcomes across diverse clinical trial data.
- Investigation of disease mechanisms and pathophysiology to identify more targeted treatment pathways.
Excerpt from the Book
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).
Summary of Chapters
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.
Keywords
Amyotrophic Lateral Sclerosis, ALS, Neuroprotection, Neurostimulation, Riluzole, Edaravone, Clinical Trials, TOS-ALS, Survival Analysis, Glutamate, Respiratory Function, Tirasemtiv, Diaphragm Pacing System, rTMS, Disease Progression
Frequently Asked Questions
What is the primary focus of this dissertation?
The work focuses on comparing various therapeutic management options for Amyotrophic Lateral Sclerosis, specifically categorizing them into neuroprotective and neurostimulating approaches.
What are the central themes of the research?
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.
What is the main objective of this study?
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.
Which scientific methods are employed in this work?
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.
What does the main body of the work cover?
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.
Which keywords characterize this publication?
Key terms include ALS, Neuroprotection, Neurostimulation, Riluzole, Edaravone, clinical trial efficacy, disease progression, and the proposed TOS-ALS classification.
How does the author define the "TOS-ALS" system?
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.
What is the significance of the Diaphragm Pacing System (DPS) in this context?
The dissertation analyzes DPS as a neurostimulating intervention, noting its use on humanitarian grounds despite mixed trial results regarding its impact on overall survival.
Why is the "Critical Analysis" section important?
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.
- Arbeit zitieren
- Dr Pranav Jha (Autor:in), 2017, Neuroprotective vs. Neurostimulating Management Options for Amytrophic Lateral Sclerosis. A Multiple Trial Based Comparison, München, GRIN Verlag, https://www.grin.com/document/542438
