Pharmaco-proteomics opportunities for individualizing neurovascular treatment

Abstract

Neurovascular disease often involves multi-organ system injury. For example, patent foramen ovale (PFO) related ischemic strokes involve not just the brain, but also the heart, the lung, and the peripheral vascular circulation. For higher-risk but high-reward systemic therapy (e.g., thrombolytics, therapeutic hypothermia, PFO closure) to be implemented safely, very careful patient selection and close monitoring of disease progression and therapeutic efficacy are imperative. For example, more than a decade after the approval of therapeutic hypothermic and intravenous thrombolysis treatments, they both remain extremely underutilized, in part due to lack of clinical tools for patient selection or to follow therapeutic efficacy. Therefore, in order to understand the complexity of the global effects of clinical neurovascular diseases and their therapies, a systemic approach may offer a unique perspective and provide tools with clinical utility. Clinical proteomic approaches may be promising to monitor systemic changes in complex multi-organ diseases – especially where the disease process can be “sampled” in clinically accessible fluid such as blood, urine and CSF. Here, we describe a “pharmaco-proteomic” approach to three major challenges in translational neurovascular research directly at bedside – in order to better stratify risk, widen therapeutic windows, explore novel targets to be validated at the bench – 1) thrombolytic treatment for ischemic stroke, 2) therapeutic hypothermia for post cardiac arrest syndrome, and 3) treatment for patent foramen ovale (PFO) related paradoxical embolic stroke. In the future, this clinical proteomics approach may help to improve patient selection, ensure more precise clinical phenotyping for clinical trials, and individualize patient treatment.

Proteomic and biomarker studies and neurological complications of pediatric sickle cell disease

“…The literature on proteomic discovery and biomarkers of neurological injury, and stroke in particular, in the general population is extensive [50, 51, 52]. A focus of this work has been the use and discovery of brain specific proteins for organ specificity, which include: neuron-specific enolase (NSE) [53], heart-type fatty acid binding protein (H-FABP) [54, 55, 56], N-methyl D-aspartate (NMDA) receptor [57], visin-like protein 1 (VLP) [58], S100B [59, 60], myelin basic protein (MBP) [61], and GFAP [62].…”

Textbook of Personalized Medicine

“…Examples of challenges include thrombolytic treatment for ischemic stroke and treatment for paradoxical embolic stroke related to patent foramen ovale (Ning et al 2013 ). In the future, such an approach may help to improve patient selection, ensure more precise clinical phenotyping for clinical trials, and individualize patient treatment.…”

2013 Thomas Willis Award Lecture

“…Therefore, it is logical for ongoing research to focus on strategies that can amplify reperfusion 8 or develop new biomarker methods for finding patients who are most responsive to therapy. 9–12 But beyond these efforts to normalize blood flow or restore blood vessel integrity, it has been difficult to find effective treatments that target fundamental cell death processes in injured neurons.…”