Technologies

Background:

Numerous studies have reported the anti-oxidant, anti-inflammatory and anti-amyloid effects of curcumin. However, its poor stability has led researchers at the Salk to design and develop curcuminoid derivatives with improved potency and pharmacokinetic properties. CNB-001 has been extensively investigated in models of traumatic brain injury (TBI), Alzheimer's disease (AD), lung inflammation and stroke. The stroke models include the rabbit small clot embolic stroke model (RSCEM)- the same model used in the development of tPA. The primary endpoint of this model is behavior based upon motor function components of the NIH Stroke Scale for human stroke. CNB-001 was found to be effective in protecting neurons in the in vitro stroke models through maintenance of ATP levels and prevention of nerve cell death. The compound significantly reduced stroke-induced behavioral deficits when given as a single subcutaneous dose of 100mg/kg, 1-hour post embolism in the rabbit model. These studies also demonstrated that the activity of CNB-001 in vivo is mediated through the maintenance of the PI3K-Akt kinase pathway and ATP levels, and the modulation of calcium-calmodulin-dependent protein kinase IIa. Additional work in models of AD has shown that CNB-001 normalizes several markers for synapse loss and oxidative stress in the hippocampus caused by AD and increases levels of BDNF and the transcription of some BDNF-responsive genes in both normal rats and AD mice. Importantly, CNB-001 clears intracellular amyloid and other aggregated proteins in the brain that accumulate with old age. Total Abeta and plaque loads are not significantly reduced in treated AD mice, but CNB-001 reduces the more toxic soluble Abeta1-42. Two studies showed that CNB-001 is very effective in treating rodent models of TBI. As CNB-001 is a potent 5 lox inhibitor, it was tested and shown to have therapeutic efficacy in a rodent model of airway inflammation and remodeling.

Keywords

Alzheimer's Disease

Asthma

Calcium Signaling

Drug Discovery

Neurodegenerative Disorders

Oxidative Stress

Parkinson's

Phosphatidylinositol 3'-kinase

Schubert5-lipoxygenase (5-LOX)

Anti-oxidant

tPA

Traumatic Brain Injury (TBI)

StrokeAmyloid-beta