Extensive frontal focused ultrasound mediated blood–brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study DOI Creative Commons
Sohee Park, Kyoungwon Baik, Seun Jeon

et al.

Translational Neurodegeneration, Journal Year: 2021, Volume and Issue: 10(1)

Published: Nov. 5, 2021

Abstract Background Focused ultrasound (FUS)-mediated blood–brain barrier (BBB) opening has shown efficacy in removal of amyloid plaque and improvement cognitive functions preclinical studies, but this is rarely reported clinical studies. This study was conducted to evaluate the safety, feasibility potential benefits repeated extensive BBB opening. Methods In open-label, prospective study, six patients with Alzheimer’s disease (AD) were enrolled at Severance Hospital Korea between August 2020 September 2020. Five them completed study. FUS-mediated opening, targeting bilateral frontal lobe regions over 20 cm 3 , performed twice three-month intervals. Magnetic resonance imaging, 18 F-Florbetaben (FBB) positron emission tomography, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) comprehensive neuropsychological tests before after procedures. Results FUS targeted a mean volume 21.1 ± 2.7 confirmed 95.7% 9.4% volume. The frontal-to-other cortical region FBB standardized uptake value ratio months procedure showed slight decrease, which statistically significant, compared pre-procedure (− 1.6%, 0.986 vs 1.002, P = 0.043). CGA-NPI score 2 weeks second significantly decreased baseline (2.2 3.0 8.6 6.0, 0.042), recovered (5.2 5.8 0.89). No adverse effects observed. Conclusions safe feasible for AD. addition, potentially beneficial AD patients.

Language: Английский

Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments DOI
Anuska V. Andjelkovic, Muyu Situ, Alí Francisco Citalán‐Madrid

et al.

Stroke, Journal Year: 2023, Volume and Issue: 54(3), P. 661 - 672

Published: Feb. 27, 2023

Cerebral endothelial cells and their linking tight junctions form a unique, dynamic multi-functional interface, the blood-brain barrier (BBB). The endothelium is regulated by perivascular components forming neurovascular unit. This review examines BBB unit changes in normal aging neurodegenerative disorders, particularly focusing on Alzheimer disease, cerebral amyloid angiopathy vascular dementia. Increasing evidence indicates dysfunction contributes to neurodegeneration. Mechanisms underlying are outlined (endothelium mediated) as therapeutic target including increasing uptake of systemically delivered therapeutics across BBB, enhancing clearance potential neurotoxic compounds via preventing dysfunction. Finally, need for novel biomarkers addressed.

Language: Английский

Citations

63
Non-Invasive Drug Delivery across the Blood–Brain Barrier: A Prospective Analysis DOI Creative Commons
Sarfaraz K. Niazi

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(11), P. 2599 - 2599

Published: Nov. 7, 2023

Non-invasive drug delivery across the blood–brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is tightly packed layer of endothelial cells that shields brain from harmful substances blood, allowing necessary nutrients to pass through. It highly selective barrier, which poses challenge delivering therapeutic agents into brain. Several non-invasive procedures and devices have been developed or are currently being investigated enhance BBB. This paper presents review prospective analysis art science address pharmacology, technology, systems, regulatory approval, ethical concerns, future possibilities.

Language: Английский

Citations

43
Repeated blood–brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial DOI Creative Commons
Alexandre Carpentier, Roger Stupp, Adam M. Sonabend

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 23, 2024

Abstract Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing safety and efficacy blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter implant was placed at end tumor resection replacing bone flap. After surgery, activation to disrupt BBB performed every four weeks either before or after infusion. The primary objective Phase 1 evaluate escalating numbers emitters using standard 3 + dose escalation. 2 opening magnetic resonance imaging (MRI). secondary objectives included clinical efficacy. Thirty-three received total 90 monthly sonications administration up nine activated without observed DLT. Grade procedure-related adverse events consisted pre syncope ( n = 3), fatigue 1), wound infection 2), pain time device connection 7). endpoint met 90% showing on MRI sonication. In 12 who just prior sonication, progression-free survival 3.1 months, 1-year overall rate 58% median 14.0 months from surgery.

Language: Английский

Citations

42
Nanozyme enabled protective therapy for neurological diseases DOI

F. C. Cheng,

Sumasri Kotha,

Miao Fu

et al.

Nano Today, Journal Year: 2024, Volume and Issue: 54, P. 102142 - 102142

Published: Jan. 3, 2024

Language: Английский

Citations

30
Emerging Wearable Acoustic Sensing Technologies DOI Creative Commons
Tao Liu,

Y. J. Mao,

Hanjie Dou

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Sound signals not only serve as the primary communication medium but also find application in fields such medical diagnosis and fault detection. With public healthcare resources increasingly under pressure, challenges faced by disabled individuals on a daily basis, solutions that facilitate low-cost private hold considerable promise. Acoustic methods have been widely studied because of their lower technical complexity compared to other solutions, well high safety threshold human body acoustic energy. Furthermore, with recent development artificial intelligence technology applied speech recognition, recognition devices, systems capable assisting interacting scenes are constantly being updated. This review meticulously summarizes sensing mechanisms, materials, structural design, multidisciplinary applications wearable devices health human-computer interaction. Further, advantages disadvantages different approaches used flexible various examined. Finally, current roadmap for future research analyzed based existing progress achieve more comprehensive personalized healthcare.

Language: Английский

Citations

4
Advances in Drug Targeting, Drug Delivery, and Nanotechnology Applications: Therapeutic Significance in Cancer Treatment DOI Creative Commons
Fatih Çiftçi, Ali Can Özarslan, İmran Cagri Kantarci

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 121 - 121

Published: Jan. 16, 2025

In the 21st century, thanks to advances in biotechnology and developing pharmaceutical technology, significant progress is being made effective drug design. Drug targeting aims ensure that acts only pathological area; it defined as ability accumulate selectively quantitatively target tissue or organ, regardless of chemical structure active substance method administration. With targeting, conventional, biotechnological gene-derived drugs body’s organs, tissues, cells can be transported specific regions. These systems serve carriers regulate timing release. Despite having many advantageous features, these have limitations thoroughly treating complex diseases such cancer. Therefore, combining with nanoparticle technologies imperative treat cancer at both local systemic levels effectively. The nanocarrier-based delivery involves encapsulating target-specific molecules into polymeric vesicular systems. Various (DDS) were investigated discussed this review article. first part passive systems, hydrogels, thermoplastics, microdevices transdermal-based second carrier nanobiotechnology (carbon nanotubes, nanoparticles, coated, pegylated, solid lipid nanoparticles smart nanogels). third part, advantages discussed, finally, market research commercial used nanotechnological approaches was included.

Language: Английский

Citations

2
Biomarkers used in Alzheimer’s disease diagnosis, treatment, and prevention DOI
Yacoubou Abdoul Razak Mahaman, Kidane Siele Embaye, Huang Fang

et al.

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 74, P. 101544 - 101544

Published: Dec. 18, 2021

Language: Английский

Citations

100
Localized blood–brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions–controlled focused ultrasound DOI Open Access
Pavlos Anastasiadis, Dheeraj Gandhi, Yutong Guo

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(37)

Published: Sept. 9, 2021

Significance The blood–brain barrier (BBB) is a critical obstacle to delivering most therapeutics into the brain. In this study, we report combined MRI, histological, and real-time acoustic emissions monitoring findings from Phase 0 clinical trial examining microbubble-enhanced transcranial focused ultrasound for controlled BBB opening in patients with infiltrating gliomas. data revealed capability of technology provide safe, controlled, tightly monitored through intact skull. Our demonstrate tune real-time, creating opportunities improved treatment brain tumors.

Language: Английский

Citations

94
Opening of the Blood–Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models DOI Creative Commons

Aria Sabbagh,

Kévin Beccaria, Xiaoyang Ling

et al.

Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 27(15), P. 4325 - 4337

Published: May 24, 2021

Abstract Purpose: The blood–brain barrier (BBB) inhibits adequate dosing/penetration of therapeutic agents to malignancies in the brain. Low-intensity pulsed ultrasound (LIPU) is a safe method temporary BBB disruption (BBBD) enhance chemotherapeutic delivery tumor and surrounding brain parenchyma for treatment glioblastoma. Experimental Design: We investigated if LIPU could efficacy anti–PD-1 C57BL/6 mice bearing intracranial GL261 gliomas, epidermal growth factor receptor variant III (EGFRvIII) chimeric antigen (CAR) T cells NSG with EGFRvIII-U87 genetically engineered antigen-presenting cell (APC)-based therapy producing T-cell attracting chemokine CXCL10 GL261-bearing mice. Results: Mice treated LIPU-induced BBBD had median survival duration 58 days compared 39 anti–PD-1, long-term survivors all remained alive after contralateral hemisphere rechallenge. CAR administration resulted significant increases CNS 24 (P < 0.005) 72 0.001) hours increased by greater than 129%, comparison alone. Local deposition CXCL10-secreting APCs glioma microenvironment enhanced infiltration during window = 0.004) markedly 0.05). Conclusions: immune an associated increase emerging technique enhancing novel therapies

Language: Английский

Citations

92
Central nervous system delivery of molecules across the blood-brain barrier DOI Creative Commons
Fabien Gosselet, Rodrigo Azevedo Loiola, Anna Roig

et al.

Neurochemistry International, Journal Year: 2021, Volume and Issue: 144, P. 104952 - 104952

Published: Jan. 2, 2021

Therapies targeting neurological conditions such as Alzheimer's or Parkinson's diseases are hampered by the presence of blood-brain barrier (BBB). During last decades, several approaches have been developed to overcome BBB, use nanoparticles (NPs) based on biomaterials, alternative methods open BBB. In this review, we briefly highlight these strategies and most recent advances in field. Limitations advantages each approach discussed. Combination functionalized NPs receptor-mediated transcytosis system with magnetic resonance imaging-guided focused ultrasound (FUS) might be a promising strategy develop theranostic tools well safely deliver therapeutic molecules, drugs, neurotrophic factors antibodies within brain parenchyma.

Language: Английский

Citations

88