Chlorophyllin: A possible new therapeutic agent for increasing frataxin levels in Friedreich'/INS;s ataxia patients

Abstract

FRDA is an autosomal recessive neurodegenerative disease characterized by multiple symptoms such as progressive spinocerebellar ataxia, sensory nerve affection,diabetesmellitus andlife-limitinghypertrophic cardiomyopathy. FRDA is caused by a GAA-trinucleotide expansion in the frataxin gene located on chromosome locus 9q13 which results in a markedly reduced expressionof frataxin, a smallmitochondrialprotein. Decreased frataxin levels cause iron accumulation in mitochondria, oxidative stress and cell damage. Searching for compounds which could possibly influence frataxin expression we found that the chlorophyllins can significantly increase frataxin expression by still an unknown mechanism. Chlorophyllin (CHL) is a water-soluble mixtureof salts of the green plant pigment chlorophyll. CHL currently has a wide range of uses, dietary and medicinal, including being a food colouring agent, a health food additive, an accelerant of wound healing and controlling urinary and faecal odours in geriatric patients. In a wide array of in vitro and in vivo assays, CHL has also been shown to exhibit antimutagenic, antigenotoxic and anticarcinogenic activities against numerous carcinogens. We show for the first time that additional to its protective properties chlorophyllin can increase frataxin expression in vitro and in vivo. Our results provide a scientific basis for a clinical pilot trial examining the effectiveness of this agent for the treatment of FRDA patients.