Preclinical Efforts Toward Acetate Supplementation Therapy

In view of the evidence presented above that brain acetate levels and myelin lipid synthesis are reduced in CD mice, correcting the acetate deficit by acetate supplementation would appear to be an obvious therapeutic approach for CD. In our preclinical efforts toward such a therapy for CD, we are currently examining glyceryl triacetate (Triacetin) and calcium acetate as potential exogenous acetate sources for delivering acetate to the brain. Glyceryl triacetate is a non-toxic glyceryl tri-ester of acetic acid that is widely used as a solvent and plasticizer in perfumery, tanning, dyes, as a food additive, a gelatinizing agent in cosmetics and is also used in external medicine. Biochemical studies on glyceryl triacetate have shown that glyceryl triacetate is hydrolyzed in vivo by all tissues of mammals including the gastrointestinal tract.53 Calcium acetate is currently approved as a drug for the treatment of kidney disease to control high blood phosphate levels.54 In preliminary studies we have found that calcium acetate is not as effective as glyceryl triacetate as an acetate source to the brain (Fig. 5). Therefore, efforts are underway for a systematic preclinical study with glyceryl triacetate.

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