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Evaluation of Holistic Treatment for ALS Reveals Possible Mechanism and Therapeutic Potential.

ABSTRACT: There has been a tremendous amount of research into the causes of Amyotrophic Lateral Sclerosis (ALS), but yet very few treatment options beyond amelioration of symptoms. A holistic approach has shown anecdotal evidence of slowing disease progression and this treatment, known as the Deanna protocol (DP), postulates that ALS is a metabolic disease caused by glutamate that induces toxicity. In this study, glutamate exposure to human motoneurons was investigated and found not to significantly affect cell viability or electrophysiological properties. However, varicosities were observed in axons suggestive of transport impairment that was dose dependent for glutamate exposure. Surprisingly, a subset of the components of the DP eliminated these varicosities. To verify this finding a human SOD1 patient-derived iPSC line was examined and significant numbers of varicosities were present without glutamate treatment, compared to the iPSC control, indicating the possibility of a common mechanism despite different origins for the varicosities. Importantly, the DP ameliorated these varicosities by over 70% in the patient derived cells as well. These results are consistent with much of the literature on ALS and give hope for treatment not only for arresting disease progression using compounds considered safe but also the potential for restoration of function.

SUBMITTER: Lavado A

PROVIDER: S-EPMC6326589 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Evaluation of Holistic Treatment for ALS Reveals Possible Mechanism and Therapeutic Potential.

Lavado Andrea A Guo Xiufang X Smith Alec St AS Akanda Nesar N Martin Candace C Cai Yunqing Y Elbrecht Dan D Tran My M Bryant Jean-Paul JP Colon Alisha A Long Christopher J CJ Lambert Stephen S Morgan Dave D Hickman James J JJ

International journal of pharmacy and pharmaceutical research 20171230 1

There has been a tremendous amount of research into the causes of Amyotrophic Lateral Sclerosis (ALS), but yet very few treatment options beyond amelioration of symptoms. A holistic approach has shown anecdotal evidence of slowing disease progression and this treatment, known as the Deanna protocol (DP), postulates that ALS is a metabolic disease caused by glutamate that induces toxicity. In this study, glutamate exposure to human motoneurons was investigated and found not to significantly affec ...[more]

PMID: 30637316

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Project description:RationaleAmyotrophic lateral sclerosis (ALS) poses a significant clinical challenge due to its rapid progression and limited treatment options, often leading to deadly outcomes. Looking for effective therapeutic interventions is critical to improve patient outcomes in ALS.Patient concernsThe patient, a 75-year-old East Asian male, manifested an insidious onset of right-hand weakness advancing with dysarthria. Comprehensive Next-generation sequencing analysis identified variants in specific genes consistent with ALS diagnosis.DiagnosesALS diagnosis is based on El Escorial diagnostic criteria.InterventionsThis study introduces a novel therapeutic approach using artificial intelligence phenotypic response surface (AI-PRS) technology to customize personalized drug-dose combinations for ALS. The patient underwent a series of phases of AI-PRS-assisted trials, initially incorporating a 4-drug combination of Ibudilast, Riluzole, Tamoxifen, and Ropinirole. Biomarkers and regular clinical assessments, including nerve conduction velocity, F-wave, H-reflex, electromyography, and motor unit action potential, were monitored to comprehensively evaluate treatment efficacy.OutcomesNeurophysiological assessments supported the ALS diagnosis and revealed the co-presence of diabetic polyneuropathy. Hypotension during the trial necessitated an adaptation to a 2-drug combinational trial (ibudilast and riluzole). Disease progression assessment shifted exclusively to clinical tests of muscle strength, aligning with the patient's well-being.LessonsThe study raises the significance of personalized therapeutic strategies in ALS by AI-PRS. It also emphasizes the adaptability of interventions based on patient-specific responses. The encountered hypotension incident highlights the importance of attentive monitoring and personalized adjustments in treatment plans. The described therapy using AI-PRS, offering personalized drug-dose combinations technology is a potential approach in treating ALS. The promising outcomes warrant further evaluation in clinical trials for searching a personalized, more effective combinational treatment for ALS patients.

Dataset Information

Evaluation of Holistic Treatment for ALS Reveals Possible Mechanism and Therapeutic Potential.

Publications

Evaluation of Holistic Treatment for ALS Reveals Possible Mechanism and Therapeutic Potential.

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