Low intensity focused ultrasound: a new prospect for the treatment of Parkinson’s disease

Abstract

Background: As a chronic and progressive neurodegenerative disease, Parkinson’s disease (PD) still lacks effective and safe targeted drug therapy. Low-intensity focused ultrasound (LIFU), a new method to stimulate the brain and open the blood-brain barrier (BBB), has been widely concerned by PD researchers due to its non-invasive characteristics.

Methods: PubMed was searched for the past 10 years using the terms ‘focused ultrasound’, ‘transcranial ultrasound’, ‘pulse ultrasound’, and ‘Parkinson’s disease’. Relevant citations were selected from the authors’ references. After excluding articles describing high-intensity focused ultrasound or non-Parkinson’s disease applications, we found more than 100 full-text analyses for pooled analysis.

Results: Current preclinical studies have shown that LIFU could improve PD motor symptoms by regulating microglia activation, increasing neurotrophic factors, reducing oxidative stress, and promoting nerve repair and regeneration, while LIFU combined with microbubbles (MBs) can promote drugs to cross the BBB, which may become a new direction of PD treatment. Therefore, finding an efficient drug carrier system is the top priority of applying LIFU with MBs to deliver drugs.

Conclusions: This article aims to review neuro-modulatory effect of LIFU and the possible biophysical mechanism in the treatment of PD, summarize the latest progress in delivering vehicles with MBs, and discuss its advantages and limitations.

KEY MESSAGES

• Neuro-modulatory effects of LIFU at the cellular or molecular level.

• Opening the BBB through the combination of LIFU and MBs.

• Biophysical mechanism of LIFU.

Keywords:

• Parkinson’s disease
• low-intensity focused ultrasound
• low intensity pulsed ultrasound
• mechanism
• microbubbles

Authors contributions

Ling Long directed the conception and drafting of the review; Yun-Xiao Zhong and Jin-Chi Liao participated in the conception and drafting of the review; Xv Liu, Hao Tian and Li-Ren Deng made critical revisions to the knowledge content; Long Ling finally approved the version to be published; and that all authors agree to be accountable for all aspects of the work.

Disclosure statement

The authors have no conflicts of interest to declare.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. Data sharing is not applicable to this article as no new data were created or analyzed in this study. The source of the figure and table provided in the article were original.

Additional information

Funding

This work was supported by the Natural Science Foundation of Guangdong Province (2018A0303130307), a grant from the Guangdong Basic and Applied Basic Research Foundation (2019A1515011739), and a grant from the Fundamental Research Funds for the Central Universities (19ykpy27).