TMPRSS6 as a Therapeutic Target for Disorders of Erythropoiesis and Iron Homeostasis.

TMPRSS6 is a serine protease highly expressed in the liver. Its role in iron regulation was first reported in 2008 when mutations in TMPRSS6 were shown to be the cause of iron-refractory iron deficiency anemia (IRIDA) in humans and in mouse models. TMPRSS6 functions as a negative regulator of the expression of the systemic iron-regulatory hormone hepcidin. Over the last decade and a half, growing understanding of TMPRSS6 biology and mechanism of action has enabled development of new therapeutic approaches for patients with diseases of erythropoiesis and iron homeostasis.ClinicalTrials.gov identifier NCT03165864.

Injectability as a function of viscosity and dosing materials for subcutaneous administration.

Injectability is a term related to the ease of parenteral administration of a dosing solution, and includes dose preparation, dose administration, ergonomics related to these procedures, pain of injection, and other adverse events at the injection site. This article focuses on force measurements related to injectability, namely: force to expel syringe contents (expulsion force - a mimic for in vivo injection force), needle-penetration force, and needle-bending force, and these results are supplemented by expulsion time measurements with 18 participants, as well as injections in a porcine model. Based on the expulsion time measurements, where 80 N injection force was found to be difficult for most people, we consider the maximum acceptable injection force to be 40 N, and recommend targeting no more than 20 N, especially if the configuration may be used in an autoinjector or similar device. The injectability of antisense oligonucleotide solutions was assessed to determine optimal dosing materials (among those evaluated) for a variety of solution viscosities. Dosing materials varied in syringe inner diameter, needle inner diameter, needle length, and needle wall thickness: standard-wall vs. thin-wall. In general, short (6-8 mm) thin-wall needles are recommended as a way to improve patient perception and comfort during subcutaneous dose administration.