Research Roundup: Mouse model of bipolar disorder shows promise, fighting cancer with Polio and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • Genetically modified mice show promise for studies of bipolar disorder. Human bipolar disorder is characterised by alternation between manic (hyperactive) and depressive (hypoactive) states, but many of its symptoms can be alleviated by treatment with lithium. A new study from Johns Hopkins University discovered that mice engineered to lack the protein ankyrin-G show manic-like states, characterised by over-excited activity and reactions, which could be ameliorated by lithium treatment. Moreover, repeated stress resulted in alternation between “mania-like” and “depression-like” status, reminiscent of human bipolar disorder. Ankyrin-G is a neuronal protein involved in the initiation of action potentials (electrical pulses used by neurons to communicate messages). “To our knowledge, this is the first robust mouse model of bipolar disorder based on a genome-wide significant risk factor for the human disorder”, said Christopher Ross, M.D., Ph.D., professor of psychiatry and behavioral sciences at Johns Hopkins.  This research was published the journal PNAS.
  • Turning “bad” fat into “good” fat could treat obesity. There are two types of adipose tissue in mammals: white fat and brown fat. Brown fat is considered “good” because, unlike white fat, it is metabolically active and burns calories to generate heat. In contrast, white fat simply stores energy and deposits around the waist, hips, and thighs. Scientists discovered that blocking a protein called PexRAP caused white fat in mice to be turned into “beige” fat, a new type of fat in between white and brown. Beige fat acts more like brown fat and may protect against obesity. Mice that were born without the PexRAP protein had more beige fat, were leaner than their littermates, and burned more calories even when they consumed the same amount of food. If PexRAP can be blocked in human fat cells, people with obesity, which represent 9% of the US population, may have an easier time reaching a healthy weight. This research was published in Cell Reports.
  • Blocking a signaling molecule in brain cells can stop the spread of aggressive brain tumors. Certain human brain cancers called high-grade gliomas are incredibly deadly with five year survival rates for some types around 10 percent. Researchers at Stanford University have uncovered a molecule that when deleted can halt the progression of these tumors. This signaling molecule, called neuroligin-3, had been shown in previous experiments to cause gliomas to grow. Working off of this knowledge, scientists put glioma cells in the brains of mice that had the neuroligin-3 gene and those whose gene had been deleted. They discovered that the cancer cells grew in the brains with neuroligin-3, but growth was halted in the neuroligin-3 deficient mice. Two inhibitors of neuroligin-3 had already been developed and so the researchers tested in mice whether either or both of these drugs would similarly halt the progression of the tumors. And they did. The senior author on the article, Michelle Monje, MD, PhD, stated, “We have a really clear path forward for therapy; we are in the process of working with the company that owns the clinically characterized compound in an effort to bring it to a clinical trial for brain tumor patients.” This research was published in the September 20th edition of Nature.
  • Fighting cancer with Polio.  In recent years, scientists have invested their interest in modified viruses, such as oncolytic viruses, which are optimized to kill cancer cells without damaging healthy tissue surrounding the cancer cells. One of these viruses is an engineered version of poliovirus, however it has been unclear how this virus manages to kill the cancer cells without harming the healthy tissue. This week, a study published in Science Translational Medicine, determined that the modified poliovirus, PVSRIPO, actually stimulates the natural immune system to specifically target the cancer cells. Normally, the immune system slows some types of tumor growth and inhibits tumors from becoming problematic, but when the immune system is suppressed this system no longer works. PVSRIPO seems to overcome immunosupression and may open doors to further cancer research targeting immunosupression.
Molecular model of poliovirus. Photo credit: Karsten Schneider/Science Photo Library
  • Ethical concerns growing after genome editing of human embryos. This week the journal Nature published results of experiments that used CRISPR-Cas9 to modify the DNA of a human embryo. They found that the gene OCT4 could steer cell fate as a fertilized egg starts to divide and proliferate. Another study, published just last month in Nature, used the same CRISPR-Cas9 method to correct specific genetic mutations in early stage human embryos. Both studies provide important insights into the biology of human embryos, and may pave new methodologies for in-vitro fertilization (IVF). Concerns are growing however because such gene-editing methods could lead to permanent modifications, and we do not yet understand the safety, accuracy, and feasibility of genome editing as a clinical tool. Thus, although this research is exciting and promising, much basic research and ethical discussions are necessary before we can take advantage of it.
  • A new antibody is able to attack 99% of HIV strains, according to studies in primates. The collaboration between NIH and the pharmaceutical Sanofi involves combining three “broadly neutralising antibodies” to create a “tri-specific anibody” which is able to tackle 99% of HIV strains. Dr Fauci, noted, “Combinations of antibodies that each bind to a distinct site on HIV may best overcome the defences of the virus in the effort to achieve effective antibody-based treatment and prevention.” Twenty-four monkeys were involved in the experiments, and none of those that received the antibodies developed an infection when they later received the HIV virus. Clinical trials are now planned for next year. This research was published in Science.

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