Epigallocatechin-3-gallate PEGylated poly(lactic-co-glycolic) acid nanoparticles mitigate striatal pathology and motor deficits in 3-nitropropionic acid intoxicated mice

Abstract

Huntington's disease (HD) is a debilitating neurodegenerative disease that affects around 5-10/100,000 individuals in developed countries. It is caused by genetic alterations in the huntingtin (htt) gene. Efforts are being made to find treatments which will correct the genetic alterations or their pathophysiological consequences associated with HD,3 however none of these options are yet available to patients. Thus, therapies that address and ameliorate the symptomatology of HD, which include motor dysfunction and a wide range of behavioural disturbances, are also needed. Epigallocatechin-3-gallate (EGCG) is a powerful compound extracted from the green tea plant that may possess beneficial effects for HD patients, but whose therapeutic success is limited because of its chemical instability. Here, we show that protective encapsulation of EGCG rendered it much more efficient in attenuating motor deficits and depression-like behaviour in a mice model of HD-like neurodegeneration. Importantly, behavioural improvement was also associated with a reduction of neuronal damage. These results, together with our previous findings using nanoparticle-encapsulated EGCG in mouse models of Alzheimer's disease and epilepsy, highlight their potential effectiveness for symptomatic treatment of neurodegenerative diseases.