Case Number CH-041

Inventors: Bruce Ames, PhD, et al.

Abstract
The invention provides compositions comprising a nitrone of the N-hydroxylamine and physiologically preferred aldehydes, and related methods, including therapy and manufacture.

Phenyl-N-t-butylnitrone (PBN) has been shown to reverse age-related oxidative changes, delay senescence, reverse mitochondrial decay, and exert a neuroprotective effect after oxidative damage from ischemia/reperfusion injury.  In their own research, the inventors have established that the anti-senescent effect attributed to PBN is caused by PBN’s decomposition product, N-t-butyl hydroxylamine in particular, and N-hydroxylamines in general rather than PBN.  The other decomposition product of PBN, benzaldehyde is toxic.

Advantage
By incorporating a physiological aldehyde, the subject nitrones can provide a variety of improvements, including improved delivery and absorption, enhanced stability and reduced toxicity, as compared with corresponding nitrones incorporating non-physiological aldehydes, such as benzaldehyde.  Preferred physiological aldehydes are subject to endogenous cellular uptake transport which facilitates delivery.    

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