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Review
. 2022 Mar 25:16:846681.
doi: 10.3389/fnins.2022.846681. eCollection 2022.

Neurotrophins as Therapeutic Agents for Parkinson's Disease; New Chances From Focused Ultrasound?

Alessandro Stefani  1 , Mariangela Pierantozzi  1 , Silvia Cardarelli  1 , Lucrezia Stefani  1 , Rocco Cerroni  1 , Matteo Conti  2 , Elena Garasto  2 , Nicola B Mercuri  2 , Carmine Marini  3 , Patrizia Sucapane  4
Affiliations
Review

Neurotrophins as Therapeutic Agents for Parkinson's Disease; New Chances From Focused Ultrasound?

Alessandro Stefani et al. Front Neurosci. .

Abstract

Magnetic Resonance-guided Focused Ultrasound (MRgFUS) represents an effective micro-lesioning approach to target pharmaco-resistant tremor, mostly in patients afflicted by essential tremor (ET) and/or Parkinson's disease (PD). So far, experimental protocols are verifying the clinical extension to other facets of the movement disorder galaxy (i.e., internal pallidus for disabling dyskinesias). Aside from those neurosurgical options, one of the most intriguing opportunities of this technique relies on its capability to remedy the impermeability of blood-brain barrier (BBB). Temporary BBB opening through low-intensity focused ultrasound turned out to be safe and feasible in patients with PD, Alzheimer's disease, and amyotrophic lateral sclerosis. As a mere consequence of the procedures, some groups described even reversible but significant mild cognitive amelioration, up to hippocampal neurogenesis partially associated to the increased of endogenous brain-derived neurotrophic factor (BDNF). A further development elevates MRgFUS to the status of therapeutic tool for drug delivery of putative neurorestorative therapies. Since 2012, FUS-assisted intravenous administration of BDNF or neurturin allowed hippocampal or striatal delivery. Experimental studies emphasized synergistic modalities. In a rodent model for Huntington's disease, engineered liposomes can carry glial cell line-derived neurotrophic factor (GDNF) plasmid DNA (GDNFp) to form a GDNFp-liposome (GDNFp-LPs) complex through pulsed FUS exposures with microbubbles; in a subacute MPTP-PD model, the combination of intravenous administration of neurotrophic factors (either through protein or gene delivery) plus FUS did curb nigrostriatal degeneration. Here, we explore these arguments, focusing on the current, translational application of neurotrophins in neurodegenerative diseases.

Keywords: BBB; MRgFUS; movement disorders; neurodegeneration; neurotrophins.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AC declared a shared affiliation, with several of the authors AS, MP, LS, RC, MC, and SC to the handling editor at the time of the review.

Figures

FIGURE 1
FIGURE 1
Box plot of changes in scores at the Fahn-Tolosa-Marin (FTM) part A side treated (range 0–9) with 2-years follow up in patients with Parkinson tremor dominant unilateral and in patients with Essential tremor.
FIGURE 2
FIGURE 2
Tremor Recurrence (13%), as estimated in a cohort of MRgFUS-treated ET patients (Sucapane, 1’Aquila).
See this image and copyright information in PMC

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