A tubulin binding molecule drives differentiation of acute myeloid leukemia cells.

Despite much progress in developing better drugs, many patients with acute myeloid leukemia (AML) still die within a year of diagnosis. This is partly because it is difficult to identify therapeutic targets that are effective across multiple AML subtypes. One common factor across AML subtypes is the presence of a block in differentiation.

A call for better understanding of target engagement in Tau antibody development.

Significant efforts have been channeled into developing antibodies for the treatment of CNS indications. Disappointment with the first generation of clinical Tau antibodies in Alzheimer's disease has highlighted the challenges in understanding whether an antibody can reach or affect the target in the compartment where it is involved in pathological processes. Here, we highlight different aspects essential for improving translatability of Tau-based immunotherapy.

Unbound Brain-to-Plasma Partition Coefficient, K-a Game Changing Parameter for CNS Drug Discovery and Development.

Purpose: More than 15 years have passed since the first description of the unbound brain-to-plasma partition coefficient (K) by Prof. Margareta Hammarlund-Udenaes, which was enabled by advancements in experimental methodologies including cerebral microdialysis. Since then, growing knowledge and data continue to support the notion that the unbound (free) concentration of a drug at the site of action, such as the brain, is the driving force for pharmacological responses.

Differentiation of Human Induced Pluripotent Stem Cells (hiPSC) into Endothelial-Type Cells and Establishment of an In Vitro Blood-Brain Barrier Model.

Development of central nervous system (CNS) therapeutics and their brain delivery is impeded by the presence of the blood-brain barrier (BBB). In vitro BBB models, in particular human in vitro BBB models, are critical tools for CNS drug research and development. However, the availability of primary human microvascular endothelial cells is very limited for in vitro modeling.

Strategies for delivering therapeutics across the blood-brain barrier.

Achieving sufficient delivery across the blood-brain barrier is a key challenge in the development of drugs to treat central nervous system (CNS) disorders. This is particularly the case for biopharmaceuticals such as monoclonal antibodies and enzyme replacement therapies, which are largely excluded from the brain following systemic administration. In recent years, increasing research efforts by pharmaceutical and biotechnology companies, academic institutions and public-private consortia have resulted in the evaluation of various technologies developed to deliver therapeutics to the CNS, some of which have entered clinical testing.