Advanced tissue technologies of blood-brain barrier organoids as high throughput toxicity readouts in drug development.

Recent advancements in engineering Complex models (CIVMs) such as Blood-brain barrier (BBB) organoids offer promising platforms for preclinical drug testing. However, their application in drug development, and especially for the regulatory purposes of toxicity assessment, requires robust and reproducible techniques. Here, we developed an adapted set of orthogonal image-based tissue methods including hematoxylin and eosin staining (HE), immunohistochemistry (IHC), multiplex immunofluorescence (mIF), and Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) to validate CIVMs for drug toxicity assessments.

Delivery of the Brainshuttle™ amyloid-beta antibody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans.

There are few treatments that slow neurodegeneration in Alzheimer's disease (AD), and while therapeutic antibodies are being investigated in clinical trials for AD treatment, their access to the central nervous system is restricted by the blood-brain barrier. This study investigates a bispecific modular fusion protein composed of gantenerumab, a fully human monoclonal anti- amyloid-beta (Aβ) antibody under investigation for AD treatment, with a human transferrin receptor 1-directed Brainshuttle™ module (trontinemab; RG6102, INN trontinemab). , trontinemab showed a similar binding affinity to fibrillar Aβ and Aβ plaques in human AD brain sections to gantenerumab.

AAV9-mediated delivery of miR-23a reduces disease severity in Smn2B/-SMA model mice.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in survival motor neuron 1 (SMN1). The molecular mechanisms underlying motor neuron degeneration in SMA remain elusive, as global cellular dysfunction obscures the identification and characterization of disease-relevant pathways and potential therapeutic targets. Recent reports have implicated microRNA (miRNA) dysregulation as a potential contributor to the pathological mechanism in SMA.

Application of Imaging Techniques to Cases of Drug-Induced Crystal Nephropathy in Preclinical Studies.

A number of drugs can cause precipitates within renal tubules leading to crystal nephropathy. Crystal nephropathy is usually an exposure-related finding and is not uncommon in preclinical studies, where high doses are tested. An understanding of the nature of precipitates is important for human risk assessment and further development.

Influence of non-spatial working memory demands on reach-grasp responses to loss of balance: Effects of age and fall risk.

Reactive balance recovery strategies following an unexpected loss of balance are crucial to the prevention of falls, head trauma and other major injuries in older adults. While a longstanding focus has been on understanding lower limb recovery responses, the upper limbs also play a critical role. However, when a fall occurs, little is known about the role of memory and attention shifting on the reach to grasp recovery strategy and what factors determine the speed and precision of this response beyond simple reaction time.

Characterization of post-surgical alterations in the bile duct-cannulated rat.

The bile duct-cannulated (BDC) rat is a standard animal model used in ADME experiments. The aim of this study was to investigate post-surgical alterations that are relevant to ADME investigations in BDC rats compared with sham- and non-operated animals. Water and food intake was reduced in the animals' post-surgery.