HIFU Varicose Vein Treatment Using Veinsound Device Feasibility Study On Sheep

The purpose of this nonclinical study was to evaluate the performance (in terms of vein occlusion) and the local tissue effects of echo-guided HIFU (High Intensity Focused Ultrasound) treatments in sheep’s saphenous veins.HIFU treatments were used to treat 4 saphenous veins. Two HIFU doses were evaluated 4s/60J and 7s/105J with and without tumescence injection in perivenous tissues. Before and after treatment, ultrasound scans were performed (at Day 0, 3, 7 and 21). Sheep were then euthanized at D21. Local tissue effects were evaluated based on the macroscopic observations, while the evaluation of the device performance was based on ultrasonic scan.Macroscopically throughout the study duration, for dose of 4s/60J and with tumescence, significant lumens diameter reduction of 84% was observed without skin burns. For doses of 4s/60J without tumescence and 7s/105J skin burns of slight to severe grade was observed along the vein, while no thrombus nor lumen reduction were observed.

Development and Regulatory Challenges for Peptide Therapeutics

There has been an increased interest in and activity for the use of peptide therapeutics to treat a variety of human diseases. The number of peptide drugs entering clinical development and the market has increased significantly over the past decade despite inherent challenges of peptide therapeutic discovery, development, and patient-friendly delivery. Disparities in interpretation and application of existing regulatory guidances to innovative synthetic and conjugated peptide assets have resulted in challenges for both regulators and sponsors. The Symposium on Development and Regulatory Challenges for Peptide Therapeutics at the 40th Annual Meeting of the American College of Toxicology held in November of 2019 focused on the following specific topics: (1) peptide therapeutic progress and future directions, and approaches to discover, optimize, assess, and deliver combination peptide therapeutics for treatment of diseases; (2) toxicological considerations to advance peptide drug-device combination products for efficient development and optimal patient benefit and adherence; (3) industry and regulatory perspectives on the regulation of synthetic and conjugated peptide products, including exploration of regulatory classifications, interpretations, and application of the existing guidances International Council for Harmonisation (ICH) M3(R2) and ICH S6(R1) in determining nonclinical study recommendations; and (4) presentation of the 2016 Health and Environmental Sciences Institute’s Genetic Toxicology Technical Committee working group assessment of genotoxicity testing requirements. Perspectives were shared from industry and regulatory scientists working in the peptide therapeutics field followed by an open forum panel discussion to discuss questions drafted for the peptide therapeutics scientific community, which will be discussed in more detail.

Unusual Incidence and Location of Renaut Bodies in Beagle Dogs in a Nonclinical Study

We identified the presence of Renaut bodies in an unusual location in Beagle dogs on a 3-month nonclinical toxicity study. These peculiar structures are commonly reported as a background finding in the sciatic nerve of dogs. In our study, however, they were also observed in autonomic nerves surrounding the adrenal gland, a location in which they have not been reported before. The incidence in both locations were 8 of 32 Beagle dogs in the sciatic nerve and 6 of 40 Beagle dogs around the adrenal gland in the dosing and/or recovery phases of the study.