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| Primate brains are similar to ours |
THE world’s first monkey genetically engineered to have Parkinson’s disease has been created by researchers in Japan, New Scientist can reveal. Other monkeys created as part of the same project mimic Alzheimer’s disease and motor neurone disease.
While many scientists were encouraged by the possibility of gaining unique insight into hard-to-treat brain disorders, the news will alarm those who feel it is wrong to use primates in research (see “Monkey experiments are a necessary evil for better medicine“).
Thanks to our close evolutionary history, the brains of primates are far more similar to ours than those of the mice, flies and worms that currently dominate brain research. Marmosets, for instance, have one partner, several offspring and make eye contact with each other.
Lack of public support has limited primate research in Europe and the US. Most neurological research in these countries focuses on mice – but it is limited in its scope. For example, hundreds of compounds that showed promise in mice with a version of Alzheimer’s have failed completely when they are given to people with the disease.
In Japan and China, opposition is muted by comparison.
Last month, Hideyuki Okano at the Keio University School of Medicine in Tokyo revealed his team’s marmoset model of Parkinson’s at the State of the Brain meeting in Alpbach, Austria.
The team modified marmosets to have mutated copies of a human gene called SNCA, which is linked to Parkinson’s disease. When this gene is faulty, a protein called alpha-synuclein builds up in the brain, disrupting and then killing the brain cells that make dopamine, a signalling chemical vital for movement.
In the three years since the engineered marmosets were born, they developed Parkinson’s symptoms in the same way people do. This began with signs of sleep disturbance in their first year, followed by the appearance of a-synuclein-associated globules, known as Lewy bodies, in their brain stems the next year.
By their third year, the monkeys began to show the characteristic tremors associated with the condition. As further evidence of how similar these monkeys are to humans with Parkinson’s, Okano showed that their tremors could be eased by giving them L-DOPA, a drug given to people with Parkinson’s to make up for the lack of dopamine.
“By their third year, the monkeys began to show the characteristic tremors of the disease“
“With these diseases, it’s very difficult to investigate what’s happening in living people, so knowledge of the brain circuits responsible are mostly unidentified,” says Okano. His team hopes to work out the key neural circuits damaged at each stage of the monkeys’ decline. “We hope to find ways to predict the onset of each symptom, and develop drugs to slow down disease progression,” he says.
In China, there are 40 breeding companies which together have 250,000 cynomolgus monkeys and 40,000 rhesus macaques that could be used for scientific research, says Mu-Ming Poo of the Chinese Academy of Sciences’s Institute of Neuroscience, and leader of a government-funded plan for a 15-year national brain project also involving genetically modified monkeys. Okano says that Japan also has colonies housing around 1000 marmosets.
“It’s getting more and more difficult for neuroscience labs in the West to do research on non-human primates,” says Terrence Sejnowski of the Salk Institute for Biological Studies in La Jolla, California, and co-organiser of the State of the Brain meeting. He hopes that researchers can produce a global brain programme that will bring together the respective strengths of teams from around the world.
Not everyone is happy with this kind of primate research being carried out at all – regardless of where in the world it is being done. “There will be many in the scientific community who, like me, will be very concerned by this research,” says Vicky Robinson, chief executive of the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research. “The availability of monkeys and less stringent regulations are poor reasons for justifying the use of these animals in research… where there’s no guarantee that the results will translate to humans any more effectively than if the scientists used other species or technologies,” she says.
“Making GM monkeys means you can study complex behaviours over longer time spans,” says Roger Barker at the University of Cambridge, who researches fetal cell treatments for Parkinson’s. But he cautions that modified monkeys are unlikely to answer all of our questions. “Most human brain diseases don’t occur because of single gene defects,” says Barker. Because of this, he says that monkeys given faulty versions of only one gene will probably be of only limited clinical relevance to each of these diseases.
This article appeared in print under the headline “Monkeys created with Parkinson’s”
https://www.newscientist.com/article/mg23030784-200-first-monkey-model-of-parkinsons/?
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