Magnetic Resonance Imaging Clinics of North America, Год журнала: 2024, Номер 32(4), С. 681 - 698
Опубликована: Июль 26, 2024
Язык: Английский
Nanoscale Advances, Год журнала: 2024, Номер 6(12), С. 3009 - 3028
Опубликована: Янв. 1, 2024
Biological barriers in the central nervous system.
Язык: Английский
Процитировано
6
Journal of Controlled Release, Год журнала: 2024, Номер 372, С. 901 - 913
Опубликована: Июль 15, 2024
Язык: Английский
Процитировано
6
Pharmaceutics, Год журнала: 2024, Номер 16(6), С. 719 - 719
Опубликована: Май 27, 2024
This review discusses the current progress in clinical use of magnetic resonance-guided focused ultrasound (MRgFUS) and other platforms to transiently permeabilize blood-brain barrier (BBB) for drug delivery neurological disorders neuro-oncology. Safety trials humans have followed on from extensive pre-clinical studies, demonstrating a reassuring safety profile paving way numerous translational Alzheimer’s disease, Parkinson’s primary metastatic brain tumors. Future directions include improving devices, exploring alternative approaches such as nanodroplets, expanding application conditions.
Язык: Английский
Процитировано
5
Parkinsonism & Related Disorders, Год журнала: 2024, Номер 121, С. 106023 - 106023
Опубликована: Фев. 2, 2024
•MRgFUS is an FDA approved, incisionless, therapy for the treatment of ET and PD.•RCTs MRgFUS targeting VIM, GPi STN demonstrate benefit.•Case series PTT also suggest significant benefit.•Low-intensity can transiently open BBB.•Future technical developments studies will further define role MRgFUS. The surgical movement disorders, primarily tremor, started with radiofrequency lesioning globus pallidus thalamus in 1950s [[1]Hassler R. Riechert T. Symptomatology & surgery extrapyramidal disorders.Med. Klin. 1958; 53: 817-824http://www.ncbi.nlm.nih.gov/pubmed/13551836PubMed Google Scholar]. While this became a state-of-the-art over following decades, bilateral lesions were associated side effects such as gait, balance, speech disturbances [[2]Krayenbühl H. Wyss O.A.M. Yasargil M.G. Bilateral thalamotomy pallidotomy parkinsonism.J. Neurosurg. 1961; 18: 429-444https://doi.org/10.3171/jns.1961.18.4.0429Crossref PubMed Scopus (61) In 70's, radiosurgery gamma knife showed promise because procedure was incisionless. However, it used ionizing radiation, target could not be confirmed real-time, effect delayed by around six months. Consequently, never mainstream [[3]Walter B.L. Vitek J.L. Surgical Parkinson's disease.Lancet Neurol. 2004; 3: 719-728https://doi.org/10.1016/S1474-4422(04)00934-2Abstract Full Text PDF (138) Then, 1997, approved deep brain stimulation (DBS) tremor which gold standard treatment, no lesion made, reversible adjustable, allowed intraoperative confirmation target, and, done bilaterally 2016, we went 'back to future' when Magnetic Resonance-guided Focused Ultrasound (MRgFUS) ablation novel, tool make disorders (Fig. 1). Since its appearance early 2000s, technology has progressively gained traction disorder community incisionless therapy. consists helmet-shaped phased array transducer 1024 elements, controlled individually refocus ultrasound beams common focal point. Guided real-time magnetic resonance imaging, pass through intact skull focus precisely onto selected targets, major advantage avoiding penetration tissue between target. When focused at high frequency (MRgHiFU) (650 kHz) continuous-wave mode, cumulative thermal dose point (target) great enough produce coagulative necrosis. During MRgHiFU procedures, verified real time MR-thermography map, clinical feedback, structural MRI. addition, initial delivery low-energy sonication allows 'test lesion' only after exam shows benefit without effects, energy (temperature) increased becomes permanent, immediate results evident [[4]Krishna V. Sammartino F. Rezai A. A review current therapies, challenges, future directions transcranial technology: advances diagnosis treatment.JAMA 2017; : 1-9https://doi.org/10.1001/jamaneurol.2017.3129Crossref (171) Scholar] 2). Conceptually, any that been treated or DBS from lesioning. there ample evidence (ventral intermediate nucleus, VIM) [[5]Elias W.J. Lipsman N. Ondo W.G. Ghanouni P. Kim Y.G. Lee W. Schwartz M. Hynynen K. Lozano A.M. Shah B.B. Huss D. Dallapiazza R.F. Gwinn Witt J. Ro S. Eisenberg H.M. Fishman P.S. Gandhi Halpern C.H. Chuang Butts Pauly Tierney T.S. Hayes M.T. Cosgrove G.R. Yamaguchi Abe Taira Chang J.W. randomized trial essential tremor.N. Engl. Med. 2016; 375: 730-739https://doi.org/10.1056/NEJMoa1600159Crossref (687) Scholar,[6]Bond A.E. D.S. Warren Harrison M.B. Sperling S.A. Wang X.-Q. Elias Safety efficacy patients medication-refractory, tremor-dominant Parkinson disease.JAMA 74: 1412https://doi.org/10.1001/jamaneurol.2017.3098Crossref (210) Scholar], pars interna (GPi) [[7]Krishna Kaplitt Baltuch G. W.-C. Martinez Fernandez del Alamo Eleopra Guridi Khemani McDannold Fasano Constantinescu Schlesinger I. Dalvi Trial disease.N. 2023; 388: 683-693https://doi.org/10.1056/NEJMoa2202721Crossref (19) subthalamic nucleus (STN) [[8]Martínez-Fernández Máñez-Miró J.U. Rodríguez-Rojas Álamo Hernández-Fernández Pineda-Pardo J.A. Monje M.H.G. Fernández-Rodríguez B. Mata-Marín Guida Alonso-Frech Obeso Gasca-Salas C. Vela-Desojo L. Randomized subthalamotomy 2020; 383: 2501-2513https://doi.org/10.1056/NEJMoa2016311Crossref (99) other structures pallido-thalamic tract (PTT) [[9]Gallay M.N. Moser Rossi Magara Strasser Bühler Kowalski Pourtehrani Dragalina Federau Jeanmonod pallidothalamic tractotomy chronic therapy-resistant disease 51 consecutive patients: single center experience.Front. Surg. 6https://doi.org/10.3389/fsurg.2019.00076Crossref (34) cerebello-thalamic (CTT) [[10]Gallay accuracy MR-guided functional neurosurgery: single-center experience 253 targets 180 treatments.J. 2018; https://doi.org/10.3171/2017.12.jns172054Crossref considered but require assessment. If, on hand, low (MRgLiFU) (220 pulsed manner, low, due physical, non-thermal, interactions. This "per se" induce neuromodulation intravenous administration bubble-rich contrast agent. convergence bubbles circulation being leveraged preclinical attempts BBB, temporarily 'loosening' tight junctions endothelial cells normally restrict drugs endovascular space into surrounding tissue. Here aim summarize data regarding a) indications Essential (ET) (PD); b) investigational PD; 3) investigations MRgLiFU. first two open-label unilateral FUS-VIM medically refractory published 2013 [[11]Elias Voss Loomba Khaled Zadicario E. Frysinger R.C. Wylie Monteith S.J. Druzgal Wintermark pilot study 2013; 369: 640-648https://doi.org/10.1056/nejmoa1300962Crossref (0) Scholar,[12]Lipsman M.L. Huang Y. Sankar Chapman tremor: proof-of-concept study.Lancet https://doi.org/10.1016/S1474-4422(13)70048-6Abstract (438) suggested might effective treat improvements both disability quality life. Soon after, colleagues pivotal follow-up analyses 3 [[13]Halpern Santini Aldrich Jung N.Y. Rosenberg Three-year prospective tremor.Neurology. 2019; 93https://doi.org/10.1212/WNL.0000000000008561Crossref (62) 5 years [[14]Cosgrove V.E. imaging–guided 5-year results.J. 2022; 1-6https://doi.org/10.3171/2022.6.JNS212483Crossref (8) Using Clinical Rating Scale Tremor (CRST), they found contralateral postural maintained > 70 % improvement years. combined scores postural, kinetic rest well writing, drawing spirals pouring cup (CRST + B) affected hand improved 55 one year, 40 score (CRST-C) decreased 67 45 As far are concerned, reported analysis adverse events (AEs) including above [[15]Fishman Krishna Yamada Igase Kashima Neurological event profile tremor.Mov. Disord. 33: 843-847https://doi.org/10.1002/mds.27401Crossref (79) They documented 443 AEs 186 grouped them three categories: 1. Frame related, pin site numbness, infection, pain; 2. Sonication headache, scalp burn, lightheadedness, nausea, vomiting; 3. Thalamotomy divided four subgroups: A) Sensory disturbances, paresthesia, dysesthesias, dysgeusia; Speech swallowing dysarthria, dysphagia; C) Balance gait ataxia; D) Weakness limb coordination. Most mild (79 %) moderate (20 %). Of 1 (n = 5) rated severe, sonication-related transient, lasting less than days post-procedure. changes most neurological (45 all AEs), none severe 91 (84 92) mild. Severe rare (3 balance deficits) December 2022. (NCT04112381) still published, previous smaller [16Iorio‐Morin Yamamoto Sarica Zemmar Levesque Brisebois Germann Loh Boutet G.J.B. Azevedo Adam Patel U. Lenis Kalia S.K. Hodaie (BEST‐FUS Phase 2 trial).Mov. 2021; 36: 2653-2662https://doi.org/10.1002/mds.28716Crossref (45) Scholar, 17Martínez-Fernández Mahendran Imbach L.L. Büchele Rodriguez-Rojas Werner Matarazzo Gonzalez-Quarante L.H. Deuschl Stieglitz Baumann C.R. staged resonance-guided case study.J. Psychiatry. 92: 927-931https://doi.org/10.1136/jnnp-2020-325278Crossref (26) 18Fukutome Hirabayashi Osakada Kuga Ohnishi imaging-guided tremor.Stereotact. Funct. 100: 44-52https://doi.org/10.1159/000518662Crossref (14) support relative safety FUS-VIM. BEST-FUS trial, 10 received second, contralateral, 9 months [[16]Iorio‐Morin primary outcome life response question; 'given what you know now, would second again', outcomes met. Improvement severity expected, more importantly, benign. After had some difficulties resolved within number missteps during 6 m tandem walking slightly up initially returned baseline There person dysarthria persisted 3-month On Spanish-Swiss study, where secondary outcome, underwent least [[17]Martínez-Fernández Six experienced instability weeks, permanent. concerned 71 total CRST (67 B, 81 C). 66 head voice respectively PD, thalamic VIM (TDPD), advanced disease. These nuclei have ablative procedures PD motor complications (MRCs), respectively, decades. explored, PTT. summary main trials each Table European Union, additional application.Table 1Main disease.ReferenceStudy designTargetNumber patientsFollow-upAdverse last (12 months)Primary outcomeBond et al., 2017 [[6]Bond Scholar]Prospective, randomized, sham-controlled, double blind trialThalamic Vim27 TDPD patients. 20 receiving 7 sham procedure3 blinded (1ary outcome), 12 labelHemiparesis n (10 Paresthesia (25 %)Ataxia (5 %)Vocal change %)62 median reduction subscores (parts on-medication active-treatment arm vs 22 sham-procedure armMartínez-Fernández 2020 double-blind trialSTN40 asymmetrical 27 13 procedure4 labelLevodopa-induced dyskinesia (7 %)Clumsy %)Dysarthria (4 %)Balance %)−53 mean MDS-UPDRS III off-medication 4.2 arm.-Between-group difference 8.1 points.Krishna 2023 trialGPi94 69 25 labelDysarthria (2 %)15 Serious 10)−69 responders rate* 32 arm.Mean MDS---UPDRS 6.0 points.-Mean IV 5.1 pointsGallay Scholar]Open-label seriesPTT47 (15 treatment)12 %)−51 off-medication.-Mean 84 rigidity, 73 bradykinesia hemibody.−100 levodopa-induced dyskinesiasAE: events; CRST: Tremor; GPi: interna; MDS-UPDRS: Movement Disorders Society-Unified Disease Scale; PD: disease; PTT: tract. STN: nucleus; TDPD: dominant VIM: ventral nucleus. Open table new tab AE: earliest placebo. Primary groups. ON-medication 62 year. quite persistent months: finger paresthesia (1), orofacial (4), ataxia hemiparesis (2), (1). authors commented encouraging, dealing learning curve, likely improve "as monitoring improves" (Table 26 TDPD, Israel long term results, relief few [[19]Sinai Nassar Sprecher Zaaroor disease: long-term Parkinsons Dis. 12: 199-206https://doi.org/10.3233/JPD-212810Crossref (23) Median hemi-CRST hemi-UPDRS month (N 26) 60 92 %, 53 61 7). permanent transient unsteadiness, ataxia, weakness, taste changes, then resolved. complete, 8 partial return. Similar Japan [[20]Yamamoto Ito Fukutake Odo Kamei YamaguchiI 1-year study.Neurol. Med.-Chir. (oa.2020-0370)https://doi.org/10.2176/nmc.oa.2020-0370Crossref (17) recently (2021) GPi, indicated MRCs. An label 20) FUS-GPi OFF-medication MDS-UPDRS-III 43 Unified Dyskinesia (UDysRS). No AE occurred frequent complication [[21]Eisenberg C.E. feasibility.J. 135: 792-798https://doi.org/10.3171/2020.6.JNS192773Crossref (28) subsequent double-blind, (3:1 ratio), sham-controlled enrolled 94 MRCs positive response, defined (improvement) points either part state OR UDysRS state, clinically meaningful worsening scale, percentage twice group (69 compared (33 active 65) 29 met criterion only, 28 criteria, 31 neither criterion. 22), these numbers 0 68 respectively. For side, 21 MDS-UPDRS-IV 48 %. Corresponding 39 who months, 30 continued included 1), visual disturbance 1) facial weakness At patient remained Anecdotally, successful presenting disabling dyskinesias [[22]Stieglitz Oertel M.F. Parkinson‐related dyskinesia—a report.Mov. Clin. Pract. 9: 647-651https://doi.org/10.1002/mdc3.13462Crossref (2) Contrary classically therapeutic neurosurgical [[23]Máñez-Miró Del Martínez-Fernández Present management systematic review.Expert Rev. Neurother. 21: 533-545https://doi.org/10.1080/14737175.2021.1911649Crossref concepts changed late 80s parkinsonian circuitry elucidated [24Aziz T.Z. Peggs Sambrook M.A. Crossman A.R. Lesion alleviation 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism primate.Mov. 1991; 6: 288-292https://doi.org/10.1002/mds.870060404Crossref (442) 25Bergman Wichmann DeLong M.R. Reversal experimental nucleus.Science. 1990; 80–https://doi.org/10.1126/science.2402638Crossref 26Guridi Herrero Luquin Guillén Rube
Язык: Английский
Процитировано
4
Cell Reports Methods, Год журнала: 2024, Номер 4(2), С. 100709 - 100709
Опубликована: Фев. 1, 2024
We establish a reliable method for selectively delivering adeno-associated viral vectors (AAVs) across the blood-brain barrier (BBB) in marmoset without need neurosurgical injection. focally perturbed BBB (∼1 × 2 mm) area 8aD of frontal cortex four adult monkeys using low-intensity transcranial focused ultrasound aided by microbubbles. Within an hour opening BBB, either AAV2 or AAV9 was delivered systemically via tail-vein In all marmosets, fluorescence-encoded neurons were observed at site perturbation, with showing sparse distribution transduced when compared to AAV9. The results are direct intracortical injections anterograde tracers into and similar (albeit sparser) long-range connectivity observed. With evidence specific region as well long-distance tracing, we framework focal noninvasive transgene delivery brain.
Язык: Английский
Процитировано
4
Journal of Neurology Neurosurgery & Psychiatry, Год журнала: 2024, Номер 95(11), С. 1089 - 1092
Опубликована: Май 17, 2024
The nigrostriatal system is especially vulnerable to neurodegeneration in Parkinson's disease (PD) and the blood-brain barrier (BBB) a limiting factor for delivery of therapeutic agents brain. This pilot study aimed demonstrate safety, feasibility tissue penetration (by 18F-Choline-positron emission tomography (PET)) MR-guided focused ultrasound (MRgFUS) simultaneous BBB opening (BBB-O) substantia nigra (SN) putamen PD.
Язык: Английский
Процитировано
4
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(23), С. 16766 - 16766
Опубликована: Ноя. 26, 2023
Recent research has unveiled intriguing insights suggesting that the body’s immune system may be implicated in Parkinson’s disease (PD) development. Studies have observed disparities pro-inflammatory and anti-inflammatory markers between PD patients healthy individuals. This finding underscores potential influence of dysfunction genesis this condition. A dysfunctional can serve as a primary catalyst for systemic inflammation body, which contribute to emergence various brain disorders. The identification several genes associated with PD, well their connection neuroinflammation, raises likelihood susceptibility. Moreover, advancing age mitochondrial weaken system, potentially implicating them onset disease, particularly among older Compromised integrity blood–brain barrier could facilitate system’s access tissue. exposure lead encounters native antigens or infections, triggering an autoimmune response. Furthermore, there is mounting evidence supporting notion gut dysbiosis might represent initial trigger inflammation, ultimately promoting neurodegeneration. In comprehensive review, we will delve into numerous hypotheses surrounding role both innate adaptive immunity PD.
Язык: Английский
Процитировано
10
Advances in Clinical Medicine, Год журнала: 2025, Номер 15(01), С. 282 - 289
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Март 3, 2025
ABSTRACT Gene therapy for neurodegenerative diseases faces significant challenges due to the blood-brain barrier (BBB), which limits drug delivery central nervous system (CNS). While clinical trials Parkinson’s disease (PD) have progressed, administration of vectors expressing enzymatic or neurotrophic factor transgenes required extensive optimization method achieve potentially therapeutic levels transgene expression. Focused ultrasound (FUS) combined with microbubbles has emerged as a promising non-invasive strategy transiently open BBB targeted gene via viral nanocarriers including recombinant adeno-associated viruses (AAVs). However, key factors influencing FUS-mediated AAV delivery, dose distribution and efficacy, remain underexplored in non-human primates (NHPs). Here, we evaluated feasibility AAV9-CAG-GFP using two portable modalities: ultrasound-guided, spherically-focused FUS (USgFUS) novel low-frequency linear array configuration imaging called theranostic (ThUS). In mice, FUS-sonicated regions exhibited 25-fold increase AAV9 biodistribution compared systemic injection alone. Extending this approach NHPs, observed up 200-fold DNA treated brain regions, PD-relevant structures. assessing translational potential technique, ThUS-mediated AAV9-hSyn-hNTRN (human neurturin) toxin mouse model PD facilitated rescue 80% 75% degenerated dopaminergic neurons substantia nigra striatum, respectively. These findings demonstrate that technologies can non-invasively enhance both mice NHPs relative what be achieved intravenous (IV) same capsid With further development, these approaches may offer clinically viable, alternative diseases. One sentence summary opening increased after vector rhesus macaques.
Язык: Английский
Процитировано
0
Expert Opinion on Drug Delivery, Год журнала: 2025, Номер unknown
Опубликована: Март 17, 2025
Introduction The blood-brain barrier (BBB) is a vascular endothelial membrane which restricts entry of toxins, cells and microorganisms into the brain. At same time, BBB supplies brain with nutrients, key substrates for DNA RNA synthesis, regulatory molecules, removes metabolic waste products from to blood. breakdown and/or dysfunction have been shown in neurogenerative disorders including Alzheimer's disease (AD). Current data suggests that these changes may initiate contribute neuronal, synaptic cognitive dysfunction, possibly other aspects neurodegenerative processes.
Язык: Английский
Процитировано
0