I’m interested in your opinions on this.
An important paper just appeared in the prestigious British journal Brain from researchers in Bordeaux, France and Lausanne, Switzerland led by Dr. Morgane Darricau, a junior scientist working with eight other scientists under senior researchers Dr. Erwan Bezard and Dr. Vincent Planche.
The work was performed using rhesus monkeys, also called “macaques,” which have been productively and frequently used in research for over a century. The researchers injected abnormal tau protein from patients with PSP into the midbrain of two macaques. As controls, they injected normal tau from the brains of two people whose autopsies showed no neurological disease into the midbrain of two other macaques. The result was that starting six months later, the first group started to show abnormal control of walking and loss of performance on a cognitive task requiring opening a box containing a treat.
The deficits progressed, and after another 12 months, the animals were euthanized. Brain tissue of the two recipients of the abnormal tau showed the same sort of tau aggregation seen in human PSP. Also, crucially, the tau abnormality had spread to several areas known to be connected to the original injection. Those areas — the putamen, caudate, globus pallidus and thalamus — are among the main sites of involvement in human PSP. They must have received the abnormality from the injection site through axons and across synapses, not by mere proximity. The two control macaques had neither symptoms nor brain abnormalities at autopsy.
Similar experiments have been done with mice over the past decade with similar results, but:
- The mice did not display the full range of PSP-related brain changes that occurred in the monkeys.
- The mouse brain’s simpler circuitry and much smaller size do not closely mimic the “environment” in which the abnormal tau spreads in human PSP.
- The types of normal tau in the brain, a mix of 3R and 4R, is like that of humans, while normal mice produce only the 3R type. (“R” is a stretch of amino acids in the tau protein that allows it to attach to the brain cells’ microtubules. The number is how many such stretches exist in the tau molecule.) This suggests that macaques and humans share a similar genetic control of tau production.
- The complexity of monkeys’ normal movements and cognitive processes more closely resemble those of humans, allowing more valid extension of the experimental observations to humans and their diseases. This complexity also allows a finer-grained evaluation of the effects of the experimental intervention.
The authors point out that while only four macaques were necessary to demonstrate this result, larger numbers would be needed to confirm the findings and to turn this model into a practical research tool. Once that happens, many research labs the world over could use this technique in studying PSP and testing drugs designed to slow, stop or reverse its progression.
Now here’s the issue at hand: The last line of the paper is:
“ . . . our results support the use of PSP-tau inoculated macaques as relevant animal models to accelerate drug development targeting this rare and fatal neurodegenerative disease.”
At one level, they are probably right: using macaques in research would bring a cure for PSP faster than using mice. But some people oppose the use of animals of this level of intelligence in scientific research, no matter the benefit to humans. I’m interested in your opinion: should macaques be used in PSP research?
No, I don’t know how many macaques might ultimately be needed. Nor do I know how much sooner a cure would be found compared to the present practice of using only rodents. So, try to provide an opinion that transcends those important specifications.
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