Synthetic oil triheptanoin improves sociability, motor skills and cell function in a mouse model of Rett syndrome
(Oct 9, 2014) In a new study, researchers report that an experimental dietary supplement – the synthetic oil triheptanoin – eased autism-like behaviors in a mouse model of Rett syndrome. The treatment also improved the mice’s previously poor motor skills.
Rett syndrome is a rare cause of autism that stems from a single gene mutation. However, the researchers, from Johns Hopkins University, expressed hope that the oil might someday help those with more-common types of autism.
Their report appears today in the open-access journal PLOS ONE.
“These results are encouraging but need to be viewed very cautiously,” comments Dan Smith, Autism Speaks senior director for discovery science. “Essential next steps include independent replication of these results and experiments demonstrating how triheptanoin works in the body to improve behavior and biology.”
The Johns Hopkins researchers speculate that the improvements seen in the treated mice may relate to how triheptanoin improves the function of mitochondria – the tiny energy factories that power our cells. Previous research has suggested links between mitochondrial defects and some types of autism, including Rett syndrome, in people.
Rett syndrome is a disorder associated with mutations in the MECP2 gene. The gene codes for a vital protein called methyl-CpG-binding-protein 2 (MeCP2). Rett syndrome’s autism-like symptoms include difficulty communicating and socializing, seizures, muscle weakness and gastrointestinal problems. Many of these symptoms are common among individuals with other types of autism.
Mitochondria and autism symptoms
Lead researcher Gabriele Ronnett says she suspected that at least some of Rett syndrome's symptoms stem from metabolic problems resulting from poor mitochondrial function. Mitochondria provide the body's cells with fuel. They are particularly crucial to the function of brain cells, which rank among the most energy-demanding.
"Rett syndrome becomes apparent in humans 6 to 18 months old, when the energy needs of the brain are particularly high because a lot of new neural connections are being made," she says. "If the mitochondria are already defective, stressed or damaged, the increased demand would be too much for them."
A mouse model of Rett syndrome
In their study, the researcher used mice lacking the MeCP2 protein. They fed them a diet enriched with the synthetic oil triheptanoin. The oil breaks down into a natural compound that supports healthy mitochondrial function. Some small studies have suggested that the oil helps people with certain metabolic disorders.
Triheptanoin is currently made for research purposes only and is not on the market as a medicine or dietary supplement.
Though far from curing the mice, the results were striking, the researchers say. Treated mice had healthier mitochondria, improved motor function, increased social interest in other mice and lived nearly a third longer than the untreated Rett-syndrome mice.
"It is still too early to assume that this oil will work in humans with ASDs, but these results give us hope," Ronnett says. Additional mouse studies are needed to perform a wider range of physiology and behavior tests and to study the treatment’s effect on the brain, the researchers conclude.
“Even if triheptanoin corrects mitochondrial dysfunction,” Dr. Smith adds, “we would still be a long way from knowing whether it corrects mitochondrial dysfunction that is relevant to people with autism spectrum disorder.”