LIPUS – Dementia

2014

Based on the idea that LIPUS treatment that improves microcirculatory insufficiency could also be effective for dementia, the basic research ( by using two types of mouse models) was started.

2017

The research project was adopted by AMED Innovative Medical Seed.

2018

A paper on the efficacy and safety in the 2 mouse models was published.

2018-2019

A phase 1 Investigator-initiated clinical trial for early Alzheimer’s disease and mild dementia was conducted to evaluate short-term safety (5 cases). Safety was certified by the Efficacy and Safety Judgment Committee.

2019-2022

A physician-led phase 2 clinical trial has been conducted to evaluate efficacy and long-term safety (22 cases). The safety profile was reaffirmed, and the findings strongly suggest efficacy towards treatment of early Alzheimer’s disease and Mild Cognitive Impairment.

2022

LIPUS-AD, a Medical Device for the Treatment of Early Alzheimer’s Disease, was granted the first Breakthrough Medical Device from the Ministry of Health, Labor and Welfare (PMDA).

2023

Phase 3 pivotal trial to evaluate the efficacy of LIPUS-AD for early Alzheimer’s disease has been initiated. The pivotal trial results are anticipated in late 2026.

2024

Target enrollment number (220 cases) reached in pivotal trial of LIPUS-AD therapy for early Alzheimer’s disease

LIPUS – Angina

2001

Pro. Shimokawa came up with the idea of angina treatment using low-intensity shock waves when he listend to a presentation of an Italy group that “Irradiation of cultured endothelial cells with low-intensity shock waves enhances nitric oxide synthase (eNOs) activity at a specific number of irradiations” at the 1st Annual Scientific Meeting of the Japanese Society of NO Society held in 2001. Then he started the basic research with his group.

2004

After several experiments, he discovered that a low-intensity shock wave, which is about one-tenth to the current lithotripsy treatment, regenerates blood vessels most efficiently. Then Prof. Simokawa group co-developed a shock wave treatment device for heart disease with a Swiss medical device company.

2004-2009

Primary (open study) and secondary (placebo-controlled, double-blind study) clinical studies were done for severe angina.

2010

Low-intensity shock wave extracorporeal therapy for severe angina was approved in Japan as advanced medical care (currently advanced medical care B).
The development of angiogenesis technology using less invasive ultrasound was started, and discovered that 32-wave low-intensity pulsed ultrasound (LIPUS) has almost the same effect as the low-power shock wave, and a patent was filed in 2009 (granted; 2014).

2013

The investigator-initiated clinical trial for severe angina using LIPUS was started at 10 hospitals nationwide, including Tohoku University Hospital.

2016

Mechanism of action of LIPUS was elucidated in detail at molecular level and a paper was published.

2019

Regarding severe angina clinical trial, LPI was done (62 patients in total) -Follow-up will be completed in December 2020 (AMED Seed C).

Shock wave ablation catheter system

2008

Based on the idea that shock waves could also be effective in treating intractable arrhythmias, the development of shock wave ablation catheter system was started.

2011-2014

The development program was adopted as JST A-STEP project, and Shock Wave Medical (currently dormant) was established at the end.

2015-2016

AMED Research Fund (Translational Research Seed B) supported the development.

2018-2020

AMED Research Fund (Medical Device Development Promotion Research Project) supported the development.
So far, three papers on efficacy and safety in the pig model have been published.

2021

AMED Research Fund (Translational Research Pre-C Project) supported the development.

2023

Shock Wave Ablation Catheter System (SWCS), a medical device for treating arrhythmia, was granted a patent in Japan. Patents granted in the U.S., EU, and Japan.