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Of Mice Not Men: Seeking a preventative malaria treatment; space mice

This is a recurring column on early-stage research in animals or other laboratory models that has not entered the clinic yet but could have implications for future research and development of human medicines.

Finding the root of the malaria problem

A research team at the University of California, San Diego has found over 600 chemical compounds that could target the malaria parasite at an earlier stage in its lifecycle, using a method that includes lighting up a type of cell from mosquitoes that delivers the malaria virus to humans called sporozoites like a firefly.

Elizabeth Winzeler, professor of pharmacology and drug discovery at UC San Diego School of Medicine, led a research team that spent two years testing over 500,000 chemical compounds that could target the malaria parasite in the human liver rather than in the bloodstream, which is later in a parasite's lifecycle and the time most current treatments target. The strategy could open the door to new preventative malaria drugs rather than current symptom-based treatment methods.

"In many ways, the search for new malaria drugs has been a search for something akin to aspirin — it makes you feel better but doesn't necessarily go after the root of [the] problem," Winzeler said in a Dec. 6 press release. The study was published Dec. 7 in Science.

Malaria is a potentially deadly parasite typically passed onto humans through mosquitoes when they feed on human blood. Symptoms of malaria include fever, chills and a flu-like illness, according to the Centers for Disease Control and Prevention.

The infection of the parasite begins in a human's liver and then spreads into the red blood cells. According to the study, symptoms are felt when the infection reaches the bloodstream. This stage is also when the parasite can be transmitted to other mosquitoes and spread to other humans, which is why treating malaria at an earlier stage of the parasite's lifecycle could be so beneficial.

SNL Image

The UC San Diego team, using a strain of malaria that only infects mice, extracted the sporozoites and engineered them to produce luciferase, the same enzyme that produces the glow in fireflies. The researchers then introduced a chemical compound to the sporozoites and, when the glow went out, they knew that the chemical had killed the parasite or blocked it from replicating. After the potency of a chemical was retested, the scientists then removed the chemicals toxic to liver cells.

This new strategy could help both treat malaria's symptoms and prevent the spread of parasites because it would kill them before they reach the bloodstream, according to the study.

Winzeler and the team will next focus on how successful the more than 600 compounds will be at targeting the liver stage of the human strain of the parasite. In order to speed the discovery process up, they have kept all of their data open source.

According to the World Health Organization's 2018 World Malaria Report, 219 million cases of malaria and an estimated 435,000 deaths were reported worldwide in 2017.

Whole-brain imaging system for mice

Scientists with the Institute of Molecular and Clinical Ophthalmology Basel developed a high-resolution ultrasound imaging system that can record the whole brain of mice during behavior, according to a study published Dec. 5 in Neuron.

Botond Roska, the lead scientist on the international team, said the new system produces images at a higher quality, in a simpler way, and at a much lower cost than the traditional functional magnetic resonance imaging, or fMRI. An fMRI is difficult to apply to "awake and behaving" mice, according to the study.

The research team, which included members from the Friedrich Miescher Institute for Biomedical Research and the Neuro-Electronics Research Flanders, said brain-wide maps will be able to provide a systematic understanding of the regions of the brain that operate for specific behaviors.

In order to test the system, scientist mapped brain activity related to the optokinetic reflex, which the study said is when the eye snaps back to the original position of an object after following the object across the horizon, either vertically or horizontally. This reflex is in both mice and humans, and uses 87 of the 181 brain regions consistently identified in animals, the study said.

SNL Image

Three groups of mice were used for the experiment: one group that had a fully functioning optokinetic reflex, one group that had a damaged reflex due to genetic disease, and one that had the reflex blocked by a mechanism placed by scientists.

The study found that regions in the thalamus associated with the reflex were inactive in the mice who lost the reflex due to genetic disease, but was active in mice that had the reflex blocked. This shows that the brain regions are "independent of the motor output of the reflex," the study said.

The scientists were surprised about the precision of the mapping. Roska said the system will be a way "for obtaining an unbiased view of brain activity in other types of behavior as well as in animal models of neurologic or psychiatric diseases."

Space may not be that great for mice

After groups of mice completed a successful journey through space, researchers found that long-term space travel negatively impacted the production of B-lymphocytes, which are white blood cells responsible for antibody production.

In a new study published Dec. 6 in the Federation of American Societies for Experimental Biology Journal, researchers examined mice after a 30-day spaceflight aboard the Bion-M1 biosatellite. NASA and the Russian Institute of Biomedical Problems, Moscow have formed a joint venture to study the biological impacts of low Earth orbit on tissues and cell growth in animals, according to NASA.

The Bion-M1 biosatellite travels at an altitude of about 575 kilometers, or 357 miles, which is similar to the altitude of the Hubble Space Telescope, according to the study.

Researchers conducted the experiment with three groups of mice: two groups launched into space and one that remained on Earth. Of the two groups launched into space, one was studied when the mice landed and the other group was studied one week after landing. Both groups were exposed to weightlessness during the flight.

After scientists examined proteins in the mice's femurs, both groups of space mice had altered immune systems compared to the mice who remained on Earth. Furthermore, the alterations did not return to the group examined one week after landing.

The study said these reductions in B-lymphocytes may explain increased susceptibility to infection seen after long durations of space travel and weightlessness.

The collection of studies being done with the Bion-M1 are meant to examine the long-term effects of weightlessness on astronauts and explore ways to improve the health of humans potentially involved in long-term missions.

"Such concerns are of major importance at a time when space agencies are envisioning manned missions to the moon, asteroids, and even Mars in the near future," Fabrice Bertile, a researcher at the Hubert Curien Multidisciplinary Institute's Analytical Sciences Department in Strasbourg, France, said in a Dec. 6 press release.