May 19, 2008

Scientists Create First Genetically Modified Primate

Scientists at Emory University have genetically engineered monkeys to have Huntington's disease in hopes of gaining a better understanding of the fatal, hereditary ailment to develop possible new treatments.

The researchers, from Emory University's Yerkes National Primate Research Center in Atlanta, said the monkeys are the first primates to be genetically modified.

Describing their work, they said one of two surviving rhesus macaque monkeys engineered to have the defective gene that causes Huntington's in humans is already is exhibiting the tell-tale signs of the disease at an age of only 10 months.  

Huntington's disease is the result of a single irregular gene that causes certain nerve cells in the brain to deteriorate.  Although people are born with the gene, symptoms of the disease do not usually appear until middle age.

While researchers frequently perform laboratory studies on animals such as mice to gain insight into the fundamental biology of various diseases, monkeys and other primates are closer to people than rodents in neurological, physiological and genetic characteristics.

"Rodent species can capture some of the characteristics of the disease, but they have not been satisfactory in being able to really capture the essence of the disease," Stuart Zola, head of the Yerkes center, said during a telephone interview with Reuters.

"Now we have a genetically modified nonhuman primate that really has captured the clinical signs that we see in patients with Huntington's disease."

Those with the progressive, degenerative disease experience uncontrolled movements, mental deterioration and emotional problems.

And while drugs can help manage symptoms, they do not prevent the mental and physical decline, and patients typically die within 10 to 15 years after symptoms appear.

The researchers said they decided to genetically modify the monkeys with Huntington's because of the simplicity of the disease, which is associated with mutations in a single gene rather than multiple genes.

Zola said the achievement could lead the way to studies of other genetically modified primates with neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease.

"This research allows scientists to advance beyond mouse models, which do not replicate all of the changes in the brain and behavior that humans with Huntington's disease experience," John Harding, a primate resources official at the National Institutes of Health, told Reuters.

Using something called viral vector technology, the researchers transferred the Huntington's gene into an egg cell of a monkey.  Through in vitro fertilization, the egg grew into a four-cell embryo and was then implanted in the womb of a female monkey acting as a surrogate mother.

Two of the five babies born using the process had died within about a day, and another one died about 30 days later.   Two are still living and are approximately 10 months old, according to Anthony Chan of the Yerkes center.   Chan said one of the two surviving monkeys is exhibiting the telltale Huntington's disease symptoms of involuntary movements of the face and hands. The other monkey has not shown any symptoms, but may develop them later, Chan said.


On the Net:

The study was funded by the National Institutes of Health, and was published in the journal Nature.  A summary can be viewed here.

Emory University