Treatment of Parkinson’s disease using focused ultrasound with GDNF retrovirus-loaded microbubbles to open the blood–brain barrier

Abstract

This study aims to prepare ultrasound-targeted glial cell-derived neurotrophic factor (GDNF) retrovirus-loaded microbubbles (M pLXSN-GDNF) to verify the properties of the microbubbles and to study the therapeutic effect of the GDNF retrovirus-loaded microbubbles combined with ultrasound (U) to open the blood–brain barrier (BBB) in a Parkinson’s disease (PD) model in rats, allowing the retrovirus to pass through the BBB and transfect neurons in the substantia nigra of the midbrain, thereby increasing the expression of GDNF. The results of western blot analysis revealed significant differences between U + MpLXSN-EGFP, U + M + pLXSN-GDNF, and M pLXSN-GDNF (P < 0.05) groups. After 8 weeks of treatment, the evaluation of the effect of increased GDNF expression on behavioral deficits in PD model rats was conducted. The rotation symptom was significantly improved in the U + MpLXSN-GDNF group, and the difference before and after treatment was significant (P < 0.05). Also, the content of dopamine and the number of tyrosine hydroxylase-positive (dopaminergic) neurons were found to be higher in the brain of PD rats in the U + M pLXSN-GDNF group than in the control groups. Ultrasound combined with GDNF retrovirus-loaded microbubbles can enhance the transfection efficiency of neurons in vivo and highly express the exogenous GDNF gene to play a therapeutic role in PD model rats.

Effect evaluation of transcatheter arterial chemoembossment combined with PD1 inhibitor in the treatment of advanced liver cancer

“…This study is a retrospective cohort study, which aims to evaluate the efficacy of TACE combined with PD-1 inhibitor and monotherapy (only PD-1 inhibitor monotherapy) in patients with advanced liver cancer [5][6]. The subjects of the study were patients with advanced liver cancer who were treated in local hospitals.…”

“Focused Ultrasound-mediated Drug Delivery in Humans – a Path Towards Translation in Neurodegenerative Diseases”

“…It is estimated that the brain capillary network in humans has a total length of 600 km, providing 15-30 m 2 surface of selectively permeable BBB and offering a highly attractive route of drug delivery into the brain in the context of disease [89]. FUS+MB has extensively shown to increase permeability of therapeutic agents in animal models of neurodegeneration including AD [90][91][92][93] and PD [94][95][96][97], leading to the reversal of some disease symptoms. With initial clinical trials showing safe BBB opening in humans [43][44][45], currently the biggest challenge is to use FUS+MB to achieve improved drug delivery in human patients in the absence of any adverse effects.…”

Physical Cue‐Based Strategies on Peripheral Nerve Regeneration

“…[65,66] This mechanism has been proven to positively mediate the secretion of neurotrophic factors such as BDNF, ciliary neurotrophic factor (CNTF), NGF, and glialcellline-derived neurotrophic factor (GDNF) by SCs, and in turn promote neuroprotection, axonal regrowth, and myelinogenesis. [17,58,[67][68][69] Continuum theory is another mechanism to interpret cell and tissue response to US. In this theory, the above-mentioned changes in gating dynamics and associated membrane permeability are deemed to be synergistic effects of US and US-induced changes in the proximal microenvironment to target cells, such as fluid flow and microjet.…”