New research indicates that acetate supplements may be an effective therapy for Canavan disease, a degenerative and ultimately fatal disorder of the brain and central nervous system.
Currently, there is no cure for Canavan disease, a recessive genetic disorder that is carried by one in 40 Ashkenazic Jews. Canavan patients have a mutation of the gene aspartoacylase, which prevents the healthy metabolism of a chemical in the brain, N-acetylasparate. The resulting buildup of the chemical turns myelin — which insulates nerve cells and allows transmission of nerve impulses —into spongy tissue.
In an April publication of the Proceedings of the National Academy of Sciences, scientists tested a theory that acetate deficiency in Canavan patients decreases synthesis of myelin-related fatty acids and lipids, which causes the disease.
In a Canavan mouse model, researchers led by Dr. Aryan Namboodiri of the Uniformed Services University of Health and Sciences in Bethesda, Md., a clinical and research center of the U.S. Department of Defense, found that acetate levels decreased by around 80% at the time of myelination. Also, a human Canavan patient showed decreased myelin lipids.
Those treating Canavan know it to be a devastating disease. Symptoms include poor muscle tone, increased head size, lack of head control and developmental delay.
“For real Canavan, there is nothing you can do [besides] basic supportive measures,” said Dr. Reuben Matalon, who identified the gene mutation resulting in Canavan in 1993, and now serves as the director of biochemical/molecular genetics and professor of pediatrics and human biological chemistry and genetics at the University of Texas Medical Branch at Galveston. At present, experimental gene therapy is being tested as a possible treatment.
Namboodiri said his research supports acetate supplements as a therapy for Canavan patients. “A major implication of these findings is that acetate supplementation is likely to provide a simple and inexpensive therapeutic approach,” said Namboodiri, who is a research assistant professor in the department of anatomy, physiology and genetics at USUHS. “We have made progress by showing that oral administration of glyceryl triacetate, an acetate precursor, results in 10- to 20-fold increases in acetate levels in the brains of mice in one to two hours.”
But neurologists treating Canavan patients may have elicited anecdotal evidence that acetate is an effective therapy.
Some years ago, the chairman of neurology at New York University’s School of Medicine, Dr. Edwin Kolodny, and his staff began administering calcium acetate, a generic drug, to Canavan patients who were deficient in acetate.
“We reasoned that if we supplemented the child with acetate, it might help them,” he said. “When we tried it on one of our patients, it improved their alertness and their behavior and the most remarkable thing is the head stopped enlarging,” Kolodny said.
At present, he added, “our hypothesis has been proven by an actual animal experimentation.”