A new potential therapeutic approach for ALS: A case report with NGS analysis

Medicine · 7 authors, 8 centres

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TL;DR

This case report describes a 75-year-old male with ALS who received personalized drug combinations guided by AI-PRS technology. The study found that a 2-drug combination of ibudilast and riluzole improved muscle strength, while a 4-drug initial combination showed positive but unsustainable trends before adverse events necessitated adaptation.

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This case report details the treatment of a 75-year-old male with ALS using a personalized approach. AI-PRS technology was used to design sequential drug combinations. An initial 4-drug regimen (ibudilast, riluzole, tamoxifen, ropinirole) showed improving trends in isometric handheld dynamometer scores and decreasing trends in biomarkers (NfL, TDP-43, CK). However, hypotension (attributed to a non-study medication) and other adverse events led to adaptations. Tamoxifen was removed due to a DVT, and ropinirole was removed due to visual problems. A 2-drug combination of ibudilast (20 mg/d) and riluzole (25 mg/d) demonstrated improvement in muscle function, which further enhanced when doses were doubled. A higher dose of ibudilast (60 mg/d) caused muscle weakness and other adverse effects. Next-generation sequencing identified genetic variants consistent with ALS. The findings warrant further validation in larger clinical trials.

STUDY TYPE

case_report

SPECIALTY

neurology

SUMMARISED BY

AI pipeline

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100% · A

ORIGINAL PAPER

PMC10906646

A new potential therapeutic approach for ALS: A case report with NGS analysis

Medicine

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ABSTRACT

Abstract Rationale: Amyotrophic 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 concerns: The 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. Diagnoses: ALS diagnosis is based on El Escorial diagnostic criteria. Interventions: This 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. Outcomes: Neurophysiological 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. Lessons: The 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. Keywords: ALS, new potential therapeutic approach, NGS

CITATION EXPORT

Chaur-Jong Hu, Po-Chih Chen, Neeraj Padmanabhan et al.. A new potential therapeutic approach for ALS: A case report with NGS analysis. Medicine. (2024). https://doi.org/10.1097/MD.0000000000037401

AUTHORS

7 · 8 CENTRES

Chaur-Jong Hu, Po-Chih Chen, Neeraj Padmanabhan, Andre Zahn, Chih-Ming Ho, Kuan Wang, Yun Yen

aDepartment of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
bDepartment of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
cDepartment of Chemical and Biomolecular Engineering Henry Samueli School of Engineering at the University of California Los Angeles, Los Angeles, CA
dDepartment of General Medicine, Taipei Medical University Hospital, Taipei City, Taiwan
eMechanical and Aerospace Engineering Henry Samueli School of Engineering University of California, Los Angeles, CA
fResearch Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan, ROC
gGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC
hCenter for Cancer Translational Research, Tzu-Chi University, Hualien, Taiwan, ROC.