Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues.

Accurately modeling healthy and disease conditions in vitro is vital for the development of new treatment strategies and therapeutics. For cardiac and skeletal muscle diseases, contractile force and kinetics constitute key metrics for assessing muscle function. New and improved methods for generating engineered muscle tissues (EMTs) from induced pluripotent stem cells have made in vitro disease modeling more reliable for contractile tissues; however, reproducibly fabricating tissues from suspended cell cultures and measuring their contractility is challenging.

ACTA1 H40Y mutant iPSC-derived skeletal myocytes display mitochondrial defects in an in vitro model of nemaline myopathy.

Nemaline myopathies (NM) are a group of congenital myopathies that lead to muscle weakness and dysfunction. While 13 genes have been identified to cause NM, over 50% of these genetic defects are due to mutations in nebulin (NEB) and skeletal muscle actin (ACTA1), which are genes required for normal assembly and function of the thin filament. NM can be distinguished on muscle biopsies due to the presence of nemaline rods, which are thought to be aggregates of the dysfunctional protein.

Creating stem cell-derived neuromuscular junctions in vitro.

Recent development of novel therapies has improved mobility and quality of life for people suffering from inheritable neuromuscular disorders. Despite this progress, the majority of neuromuscular disorders are still incurable, in part due to a lack of predictive models of neuromuscular junction (NMJ) breakdown. Improvement of predictive models of a human NMJ would be transformative in terms of expanding our understanding of the mechanisms that underpin development, maintenance, and disease, and as a testbed with which to evaluate novel therapeutics.

Aripiprazole Lauroxil NanoCrystal Dispersion Technology (Aristada Initio).

Nonadherence to antipsychotic medications for the treatment of schizophrenia is a widely recognized concern, leading to poorer clinical outcomes and higher treatment costs. Long-acting injectable (LAI) antipsychotics offer an extended dosing interval option for patients, although the current options may require an oral overlap at initiation. Aripiprazole lauroxil is an LAI that offers multiple dosing options but requires oral treatment overlap during initiation for the first 21 consecutive days.