Antisense molecules may hold promise in treating brain chemical problems such as Alzheimer's

Oct 25 2005

Saint Louis University research shows a new class of drugs may hold promise in treating brain chemical problems such as Alzheimer's disease, says the principal investigator of research published in an early on-line version of Peptides.

"We found that we can develop antisense - which is a molecular compound - to cross the blood brain barrier enough to alter brain function. This can have a profound effect on treating diseases that occur because there is too much or too little of a certain kind of protein in the brain," says William A. Banks, M.D., professor of geriatrics and pharmacological and physiological sciences at Saint Louis University and principal investigator.

"The blood brain barrier is the Holy Grail - it's the most difficult tissue to pass through."

The article will run in the April print issue of Peptides.

Antisense molecules are very specific compounds that scientists can create to plug into genetic pathways and block certain genes from producing harmful proteins.

Many scientists believe that overproduction of the amyloid beta protein in the brain causes Alzheimer's disease. Previous Saint Louis University research has found that scientists can develop antisense to cross the blood brain barrier and lower levels of amyloid beta protein in mice.

Banks tested whether the antisense theory could be generalized to reduce other brain chemicals in a mouse study involving a different protein - the brain chemical methionine enkephalin (Met-Enk).

Low brain levels of Met-Enk trigger alcohol consumption. High levels of Met-Enk cause animals to drink less.

His study team created three different antisense compounds, which lowered brain levels of Met-Enk and caused mice to drink more alcohol.

"The antisense inhibited the brain's production of Met-Enk and, as predicted, the animals drank more," says Banks, who also is a staff physician at Veterans Affairs Medical Center in St. Louis.

"We found that the antisense molecules, especially when given as a cocktail of three antisense compounds, decreased Met-Enk in the brain and increased alcohol drinking."

The study is important in learning about alcoholism, Banks says. "This is a new level of evidence that Met-Enk is involved in alcohol drinking, seizures, and maybe alcoholism and alcohol withdrawal seizures," he says.

Theoretically, scientists could develop an antisense that targets the brain chemical responsible for producing more Met-Enk as a possible treatment for alcoholism, Banks says.

But the findings are even more significant because they suggest that scientists can develop compounds that cross the blood brain barrier and turn off messenger genes that instruct cells to make or break down proteins in the brain that cause certain diseases, such as Alzheimer's disease, Banks says.

"We think our findings are going to be applicable in a general sense. This may stimulate the development of a new class of drug," Banks says. "We've had success making antisense that can get into the brain. The alcohol results are fascinating, but the big story is drug development."