There are currently no approved medications for frontotemporal dementia (FTD) and existing treatments for Alzheimer’s (AD) have limited efficacy and focus primarily on relieving symptoms rather than slowing the underlying disease. Thus, there is a major demand for new treatments, but, despite significant efforts, few drug candidates have shown promising results. Cogentis’ unique solution is to target a key brain enzyme called CDK5 that is hyperactivated in brains with FTD, AD as well as other tauopathies and plays a key role in disease progression. Our lead compound, CT-526, inhibits abnormal CDK5 activity and is one of the only candidates that targets all the major hallmarks of the selected neurodegenerative diseases: beta amyloid plaques and neurofibrillary tangles leading to cell death. In a pre-clinical AD animal model, CT-526 reversed memory loss as well as other brain deficits and significantly extended lifespan, with no detectable toxic side effects.


Select Publications on CDK5 and CT526

Shukla V et al. TFP5, a Peptide Inhibitor of Aberrant and Hyperactive Cdk5/p25, Attenuates Pathological Phenotypes and Restores Synaptic Function in CK-p25Tg Mice. J Alzheimers Dis. 2017. View article

Ji YB et al. TFP5 peptide, derived from CDK5-activating cofactor p35, provides neuroprotection in early-stage of adult ischemic stroke. Sci Rep. 2017. View article

Cardone A et al. Computational study of the inhibitory mechanism of the kinase CDK5 hyperactivity by peptide p5 and derivation of a pharmacophore. J Comput Aided Mol Des. 2016. View article

Binukumar BK et al. Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease. Mol Biol Cell. 2015. View article

Tan X et al. The inhibition of Cdk5 activity after hypoxia/ischemia injury reduces infarct size and promotes functional recovery in neonatal rats. Neuroscience. 2015. View article

Binukumar BK et al. TFP5, a peptide derived from p35, a Cdk5 neuronal activator, rescues cortical neurons from glucose toxicity. J Alzheimers Dis. 2014. View article

Zheng YL et al. Cdk5 inhibitory peptide (CIP) inhibits Cdk5/p25 activity induced by high glucose in pancreatic beta cells and recovers insulin secretion from p25 damage. PLoS One. 2013. View article

Shukla V et al. A truncated peptide from p35, a Cdk5 activator, prevents Alzheimer’s disease phenotypes in model mice. FASEB J. 2013. View article

Shukla V et al. Deregulated Cdk5 activity is involved in inducing Alzheimer’s disease. Arch Med Res. 2012. View article

Zheng YL et al. A 24-residue peptide (p5), derived from p35, the Cdk5 neuronal activator, specifically inhibits Cdk5-p25 hyperactivity and tau hyperphosphorylation. J Biol Chem. 2010. View article