Scientists have created monkeys genetically modified to have Huntington's disease in an effort to gain a deeper understanding of the fatal ailment and uncover clues to possible new treatments.
In the journal Nature on Sunday, the researchers said one of two surviving rhesus macaque monkeys engineered to have the defective gene that causes Huntington's in humans already is showing tell-tale symptoms at age 10 months.
Huntington's — incurable and hereditary — is caused by a single abnormal gene in which certain nerve cells in the brain waste away. People are born with the gene but symptoms typically do not appear until middle age.
Researchers often study laboratory animals such as mice to get insights into the underlying biology of diseases. But monkeys and other primates are more similar to people than rodents in physiological, neurological and genetic features.
The scientists at Emory University's Yerkes National Primate Research Center in Atlanta said the monkeys are the first primates genetically modified to have a human disease.
They hope studying the monkeys will allow for greater knowledge of Huntington's and ideas for new drugs.
"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 in a telephone interview.
"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, emotional disturbances and mental deterioration.
Drugs can help manage symptoms but do not stop the physical and mental decline. People typically die within 10 to 15 years after symptoms arise.
Gene change could lead to future studies
The researchers said they chose Huntington's as the disease for creating the genetically modified monkeys with an eye toward simplicity — because it is linked to mutations in a single gene rather than multiple genes.
Zola said the achievement could pave the way for creating genetically modified primates with other neurodegenerative ailments such as Parkinson's disease and Alzheimer'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," said John Harding, a primate resources official at the National Institutes of Health, which funded the study.
Using so-called viral vector technology, the researchers transferred the Huntington's gene into a monkey egg cell. After using in vitro fertilization, the egg grew into a four-cell embryo and was then placed in the womb of a female monkey acting as a surrogate mother.
Of the five baby monkeys born using this process, two died within about a day, another one died in about a month and two are still living at age 10 months, according to Anthony Chan of the Yerkes center and Emory University School of Medicine,
One of the two surviving monkeys has developed symptoms including involuntary movements of the hands and face, Chan said. The other has no symptoms of the disease yet but may develop them later, he added.