Abstract Details

Title Ropinirole Hydrochloride Remedy for Amyotrophic Lateral Sclerosis

Topic General Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 4-052

Objective We are starting randomized clinical trial testing ropinirole hydrochloride in ALS patients in December, 2018.

Background

No effective treatment has been established for patients with amyotrophic lateral sclerosis (ALS). It may imply a limitation of animal model (e.g. transgenic animal models with SOD-1 mutations) for drug development. Thus, we performed drug screening using motor neurons (MNs) derived from disease-specific-induced pluripotent stem cells (iPSC) for ALS and we found that ropinirole hydrochloride inhibited reactive oxygen species (ROS) and the abnormal aggregation of TDP-43 or FUS, improved mitochondrial function, and prevented motor neuron death (Fujimori K, Okano H, et al. Nat Med 2018). Now, we are planning a randomized clinical trial testing ropinirole hydrochloride in ALS patients.

Design/Methods This is a phase I/IIa randomized, double-blind, placebo-controlled, single-center (Keio University, Japan), open-label continuation clinical trial. The primary aim is to assess the safety and tolerability of ropinirole hydrochloride in patients with ALS. Secondary aims include the following effectiveness evaluations: ALS Functional Rating Scale-Revised, quantitative muscle strength by hand-held dynamometer, muscle volume by muscle CT scan, forced vital capacity, physical activity by activity tracker, survival, quality of life for ALS patients (ALSAQ40 scale), and Zarit Caregiver Burden Interview. Moreover, we will performed an efficacy evaluation using subjects-derived iPSCs/MNs and assess plasma/CSF biomarkers (TDP-43, and ALS-related RNA/micro RNA) as exploratory research.

Results Ropinirole hydrochloride potentially targets multiple mechanisms in ALS (i.e., oxidative stress, mitochondrial dysfunction, and abnormal aggregation of TDP-43/FUS protein, which is representative of the ALS phenotype), with promising preclinical study results based on iPSCs research. This drug has been approved for the treatment of Parkinson disease for many years; the availability of the drug suggests that rapid translation to daily clinical use might be possible.

Conclusions Our trial will provide reliable and important data for further potential trials. The results will appear in March, 2021.

Authors/Disclosures
Shinichi Takahashi, MD (Saitama med univ International med ctr, Neurology and Stroke) PRESENTER	The institution of Dr. Takahashi has received research support from JSPS KAKENHI. The institution of Dr. Takahashi has received research support from Eisai Japan. The institution of Dr. Takahashi has received research support from Bayer Japan. The institution of Dr. Takahashi has received research support from Boehringer Ingelheim Japan.
Satoru Morimoto	Satoru Morimoto has nothing to disclose.
	No disclosure on file
	No disclosure on file
Masashi Aoki, MD, PhD (Day Neuromuscular Research Laboratory)	Masashi Aoki, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Tanabe Mitsubishi.
Norihiro Suzuki	No disclosure on file
Jin Nakahara, MD, PhD, FAAN (Keio University School of Medicine)	Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mitsubishi-Tanabe. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Prof. Nakahara has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Chugai. Prof. Nakahara has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Mitsubishi-Tanabe. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for The Japanese Society for Internal Medicine. The institution of Prof. Nakahara has received research support from Chugai. The institution of Prof. Nakahara has received research support from Japan Society for the Promotion of Science.

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