Combination Therapy for Multi-Target Manipulation of Secondary Brain Injury Mechanisms.

Combination Therapy for Multi-Target Manipulation of Secondary Brain Injury Mechanisms. Curr Neuropharmacol. 2017 Aug 28;: Authors: Somayaji MR, Mahadevabharath R, Przekwas, Andrzej J, Gupta, Raj K Abstract Traumatic brain injury (TBI) is a major healthcare problem that affects millions of people worldwide. Despite advances in understanding and developing preventative and treatment strategies using preclinical animal models, clinical trials to date have failed, and a "magic bullet" for effectively treating TBI-induced damage does not exist. Thus, novel pharmacological strategies to effectively manipulate the complex and heterogeneous pathophysiology of secondary injury mechanisms are needed. Given that goal, this paper discusses the relevance and advantages of combination therapies (COMTs) for "multi-target manipulation" of the injury cascade by administering multiple drugs to achieve an optimal therapeutic window of opportunity (e.g., temporally broad window) and compares these regimens to monotherapies that manipulate a single target with a single drug at a time. Furthermore, we posit that integrated mechanistic multiscale models that combine primary biomechanics, secondary injury mechano-/neurobiology, pharmacology and mathematical programming techniques could account for vast differences in the biological space and time scales and help to accelerate drug development, optimize combination pharmacotherapy protocols and improve trea...
Source: Current Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Neuropharmacol Source Type: research