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

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.

Band-specific features of EEG connectome in patients with early-stage Parkinson's disease

“…Finally, EEG-based band-specific connectivity analysis could be more useful than fMRI in identifying innovative targets for transcranial electrical and magnetic neuromodulation or focused ultrasound techniques (Stefani et al, 2022), which are increasingly showing value as symptomatic or also disease-modifying therapies in other neurodegenerative neurological diseases (Koch et al, 2022).…”

Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia

“…Therefore, the evaluation of the effects of using adeno-associated viral vectors carrying the BDNF or GDNF gene in various CNS pathologies is highly relevant. There are a number of papers devoted to the protective effect of these vectors in various neurodegenerative diseases, such as retinal neurodegeneration, Alzheimer’s disease, Parkinson’s disease, and others [ 37 , 38 , 39 , 40 ]. However, studies on the possibility of using genetic engineering approaches that induce overexpression of neurotrophic factors to correct ischemic damage have just begun to emerge.…”

Parkinson's Disease: Current Status, Diagnosis, and Treatment Using Nanomedicines

“…Noninvasiveness; temporally opens the BBB; enhances drug delivery to the brain Requires a large amount of energy; need more clinical trial [38,41] Peptide-based technology Good BBB permeability; low antigenicity; easy to synthesize Potentially degraded by exo-and endo-peptidase; too rapid clearance [42,43] Adeno-associated virus (AAV) vectors Nonpathogenic; good BBB permeability; efficient entry genetic material to target cell Small loading capacity of therapeutic materials; limited transgene carrying capacity [40,44] the diagnosis and treatment of PD. The transferrin, insulin, and other selective transport of larger endogenous molecules are usually delivered by the RMT route.…”

“…Table 1 reveals various types of technology to cross BBB and their advantages and limitations. [38,[41][42][43]…”

“…They need for more clinical trials, limited application, and lack of experimental reproducibility. [41,39,40] In recent years, many researchers have worked hard to design and develop new BBBcrossing advanced technologies to enhance the drug penetration and ensure an efficient drug delivery. In reality, such advanced technologies are bringing more precise and accurate drug delivery systems for targeted delivery to the brain.…”