scholarly journals Blood–Brain Barrier Driven Pharmacoresistance in Amyotrophic Lateral Sclerosis and Challenges for Effective Drug Therapies

2017 ◽  
Vol 19 (6) ◽  
pp. 1600-1614 ◽  
Author(s):  
Loqman A. Mohamed ◽  
Shashirekha Markandaiah ◽  
Silvia Bonanno ◽  
Piera Pasinelli ◽  
Davide Trotti
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Blood Brain Barrier ◽  
Effective Drug ◽  
Brain Barrier ◽  
Blood Brain ◽  
Lateral Sclerosis

scholarly journals First-in-human trial of blood–brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Agessandro Abrahao ◽  
Ying Meng ◽  
Maheleth Llinas ◽  
Yuexi Huang ◽  
Clement Hamani ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Primary Motor Cortex ◽  
Brain Barrier ◽  
Human Trial ◽  
Blood Brain ◽  
Lateral Sclerosis ◽  
Bbb Opening

Abstract MR-guided focused ultrasound (MRgFUS) is an emerging technology that can accurately and transiently permeabilize the blood-brain barrier (BBB) for targeted drug delivery to the central nervous system. We conducted a single-arm, first-in-human trial to investigate the safety and feasibility of MRgFUS-induced BBB opening in eloquent primary motor cortex in four volunteers with amyotrophic lateral sclerosis (ALS). Here, we show successful BBB opening using MRgFUS as demonstrated by gadolinium leakage at the target site immediately after sonication in all subjects, which normalized 24 hours later. The procedure was well-tolerated with no serious clinical, radiologic or electroencephalographic adverse events. This study demonstrates that non-invasive BBB permeabilization over the motor cortex using MRgFUS is safe, feasible, and reversible in ALS subjects. In future, MRgFUS can be coupled with promising therapeutics providing a targeted delivery platform in ALS.

scholarly journals Altered Blood-Brain Barrier and Blood-Spinal Cord Barrier Dynamics in Amyotrophic Lateral Sclerosis: Impact on Medication Efficacy and Safety

2021 ◽  
Author(s):  
Yijun Pan ◽  
Joseph Nicolazzo
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Large Body ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Spinal Cord Barrier ◽  
The Brain ◽  
Lateral Sclerosis

The access of drugs into the central nervous system (CNS) is regulated by the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). A large body of evidence supports perturbation of these barriers in neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Modifications to the BBB and BSCB are also reported in amyotrophic lateral sclerosis (ALS), albeit these modifications have received less attention relative to those in other neurodegenerative diseases. Such alterations to the BBB and BSCB have the potential to impact on CNS exposure of drugs in ALS, modulating the effectiveness of drugs intended to reach the brain and the toxicity of drugs that are not intended to reach the brain. Given the clinical importance of these phenomena, this review will summarise reported modifications to the BBB and BSCB in ALS, discuss their impact on CNS drug exposure and suggest further research directions so as to optimise medicine use in people with ALS.

scholarly journals Blood–Brain Barrier Disruption Is Not Associated With Disease Aggressiveness in Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Tino Prell ◽  
Benjamin Vlad ◽  
Nayana Gaur ◽  
Beatrice Stubendorff ◽  
Julian Grosskreutz
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Blood Brain Barrier ◽  
Rating Scale ◽  
Cross Sectional Study ◽  
Brain Barrier ◽  
Cross Sectional ◽  
Blood Brain Barrier Disruption ◽  
Progression Model ◽  
Blood Brain ◽  
Lateral Sclerosis

The pathogenesis of the fatal neurodegenerative condition amyotrophic lateral sclerosis (ALS) remains to be fully understood. Blood–brain barrier damage (BBBD) has been implicated as an exacerbating factor in several neurodegenerative conditions, including ALS. Therefore, this cross-sectional study used the novel D50 progression model to assess the clinical relevance of BBBD within a cohort of individuals with either ALS (n = 160) or ALS mimicking conditions (n = 31). Routine laboratory parameters in cerebrospinal fluid (CSF) and blood were measured, and the ratio of CSF to serum albumin levels (Qalb) was used as a proxy measure of BBBD. In the univariate analyses, Qalb levels correlated weakly with disease aggressiveness (as indicated by individual D50 values) and physical function (as measured by ALS Functional Rating Scale). However, after adjustment for cofactors in the elastic net regularization, only having limb-onset disease was associated with BBBD. The results reported here emphasize the clinical heterogeneity of ALS and the need for additional longitudinal and multi-modal studies to fully clarify the extent and effect of BBBD in ALS.

Disruption of blood-brain barrier in amyotrophic lateral sclerosis: an update

2012 ◽  
Vol 6 (1) ◽  
pp. 64-70 ◽  
Author(s):  
L. V. Brylev ◽  
M. N. Zakharova ◽  
I. A. Zavalishin ◽  
N. V. Gulyaeva
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Lateral Sclerosis

Pediatric glioblastoma target-specific efficient delivery of gemcitabine across the blood–brain barrier via carbon nitride dots

Nanoscale ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 7927-7938 ◽  
Author(s):  
Piumi Y. Liyanage ◽  
Yiqun Zhou ◽  
Abdulrahman O. Al-Youbi ◽  
Abdulaziz S. Bashammakh ◽  
Mohammad S. El-Shahawi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Carbon Nitride ◽  
Drug Efficacy ◽  
Effective Drug ◽  
Brain Barrier ◽  
Drug Conjugation ◽  
Blood Brain ◽  
Efficient Delivery ◽  
Pediatric Glioblastoma ◽  
Selective Target

A carbon nitride dot nanocarrier system with effective drug conjugation and selective target delivering to achieve enhanced drug efficacy on pediatric glioblastomas, while proving capability to penetrate blood–brain barrier.

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