In vivo inhibition of Aβ production by memapsin 2 (β-secretase) inhibitors
Bibliographic
Development of clinically useful memapsin 2 (BACE1) inhibitors is generally thought to be very challenging because they must be small enough (generally < 500 Da) to penetrate the blood–brain barrier (BBB) yet manifest high potency and other desirable pharmaceutical properties. Previously, the authors reported structure-based design of memapsin 2 inhibitors, Fs[OM99-2] and Fs[OM00-3], with high potency but poor BBB penetration. To increase BBB and cellular permeability carrier proteins (CPs) tat and DR9 were covalently linked to these two inhibitors; the conjugated inhibitors were delivered by i.p. injection to Tg2576 mic. The data showed that treatment of Tg mice with CP-linked inhibitors resulted in significant decrease of Aβ levels in the plasma and brain.
Therapeutic Agent
Animal Model
Experimental Design
Age of Animal not exactly known. Authors' gave range of 6-15 months.Regarding frequency of administration, taken from article. - "Blood was sampled from animals prior to injection and at time intervals following injection either from the orbital sinus of anesthetized animals or from the saphenous vein with collection into heparinized capillary tubes."