Neuroprotection and the cytoskeleton: updates on the drug candidate, davunetide
Davunetide (NAP) that is derived from activity-dependent neuroprotective protein (ADNP) protects the neuronal and glial cytoskeleton and inhibits apoptosis (Gozes 2011). Recent studies showed that NAP enhances novel object recognition in the STOP heterozygous mouse - a microtubule associated protein (MAP) - deficient model of schizophrenia (Merenlender-Wagner et al. 2010, Gozes 2011). In mice overexpressing alpha-synuclein – a model for idiopathic Parkinson disease - intranasal NAP improved motor function and reduced alpha-synuclein inclusions (Fleming et al. 2011). In a mouse model of brain lesion mimicking cerebral palsy (5), NAP potently protected against ibotenate-induced excitotoxic damage in the cortical plate and the white matter of P5 mice as well as against brain lesions of P0 mice (Sokolowska et al. 2011). NAP neuroprotective effects were also demonstrated in laser-induced retinal lesions in rats. Intravitreal treatment had an early short-term effect while the effect of systemic administration was delayed and prolonged (Belokopytov et al. 2011). Intranasal NAP administration in conditions of hypobaric hypoxia resulted in increased expression of Nrf2, the master regulator of antioxidant defense system coupled to improved performance in memory in rats (Sharma et al. 2011). In vitro, NAP diminished the characteristic increase in axonal branching that accompanies tau depletion, protecting against katanin-based loss of microtubules that is accompanied by neurodegenetation (Sudo and Bass 2011). Together, these studies suggest that davunetide (NAP) has a broad range of neuroprotective effects, and is now being tested in a Phase II/III study of PSP (Allon Therapeutics Inc.).
- Gildor Chair, Adams Super Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Allon Therapeutics Inc., Vancouver, BC, Canada
- Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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