Who would have thought that "kennel cough" could one day be responsible for suppressing feverish coughs in humans? Also this week, more we can learn from monkeys.
Vaccine Delivery Going to the Dogs
A virus that commonly infects dogs, causing "kennel cough," may serve as a useful delivery vector for immunizations against influenza and other infections in humans, researchers reported in PLoS ONE.
Using common viruses such as adenoviruses for vaccine delivery is not a new concept, but past efforts have been less than successful. One reason for this has been that if the recipient already has developed immunity to the virus, the immune system is likely to destroy it rapidly, before it can perform its delivery task.
But parainfluenza virus 5 is a self-limiting infection in dogs, and in a series of experiments, led by Biao He, PhD, of the University of Georgia in Athens, Ga., beagles with prior exposure mounted a new immune response when infected with a recombinant form of the virus. However, the response was delayed, relying on cell-mediated immunity, which would allow a window of opportunity for vaccine delivery.
The researchers also emphasized the safety of the virus, in that most humans carry antibodies for it without experiencing illness. In addition, it is an RNA virus, so would have no potential unintended consequences of host cell DNA recombination. Efforts are under way to explore this vector as a possible means of immunization for H5N1 influenza – bird flu – as well as for tuberculosis and malaria, according to He.
-- Nancy Walsh
To SIRT with Love: Promise for Huntington's Disease
A new inhibitor of the enzyme SIRT2 (sirtuin 2 deacetylase) protected against some of the effects of Huntington's disease in two mouse models.
Previous laboratory and animal studies showed that inhibition of SIRT2 limited brain damage in models of Huntington's disease and Parkinson's disease. So Aleksey Kazantsev, PhD, of Massachusetts General Hospital, and colleagues tested a more powerful SIRT2 inhibitor, called AK-7, in two mouse models characterized by motor symptoms and neuronal damage similar to that seen with Huntington's disease.
In one of the mouse models, the treated animals retained more motor function, had less brain atrophy, and had less accumulation of mutant huntingtin protein in the brain compared with untreated mice. They also lived 13% longer.
In the other model, which is genetically closer to the human disease, treated animals did not have the decline in motor activity seen in untreated mice and had reduced build-up of mutant huntingtin protein in the brain.
The findings "support the further development of SIRT2 inhibitors for testing in humans," the researchers wrote in Cell Reports.
-- Todd Neale
Slimming Down the Monkeys
Fibroblast growth factor 21 (or FGF21) is emerging as an important player in energy and glucose metabolism – transgenic animals with extra FGF21 are resistant to obesity, while those with the factor knocked out are prone to impaired glucose tolerance, increased body weight, and fatty liver.
But FGF21 has poor pharmacokinetic properties, making it a poor choice for a therapy. Now, researchers led by Yang Li, PhD, of Amgen in South San Francisco have developed a monoclonal antibody, dubbed mimAb1, that mimics the actions of FGF21, but with more long-lasting effects.
In obese monkeys, they reported in Science Translational Medicine, injections of the antibody 2 weeks apart led to a 10% loss of body weight 5 to 6 weeks after the first shot, despite only small changes in the animals' food intake. Li and colleagues said the finding opens the door to an "innovative therapeutic approach to diabetes and obesity" but cautioned that more research is needed.
-- Michael Smith
Researchers Spot Lung Tumor Growth Gene
Non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) gene mutations may also have higher than normal genes tied to the growth of lung tumors, researchers wrote online in the American Journal of Pathology.
The researchers, led by Landon Inge, PhD, of St. Joseph's Hospital and Medical Center in Phoenix, found "Fn14 (fibroblast growth factor-inducible 14) levels correlate with [mutated EGFR] expression" in samples of resected tumors from NSCLC patients.
The team also found that "over-expression of Fn14 enhances lung tumor formation and metastasis" and that "suppression of Fn14 reduces metastasis in NSCLC" in tests done in rat lung epithelial cells.
They concluded that the Fn14 gene may be a new target for novel therapies in NSCLC patients, "in particular for those with EGFR-driven tumors who have either primary or acquired resistance to EGFR tyrosine kinase inhibitors."
-- Cole Petrochko
A Pep Shot for Weakened Muscles
Injections of the recombinant Wnt7a protein may help regenerate muscle fibers destroyed by Duchenne muscular dystrophy, Canadian researchers found.
The degenerative disease leads to muscle weakness and fragility that typically kills individuals by their 20s or 30s.
In a mouse model of the disease, Wnt7a injections nearly doubled muscle strength, bringing it almost back to normal levels. The treated mice also showed less damage with muscle contraction, as reported in Proceedings of the National Academy of Sciences.
Testing in human muscle samples from healthy individuals suggested a potential benefit as well. The effect of Wnt7a is thought to be through both muscle growth and stem cell expansion.
"This is also exciting because we think it's a therapeutic approach that could apply to other muscle-wasting diseases," said Michael Rudnicki, PhD, of the University of Ottawa, Ontario, and a founding member of the company developing the recombinant protein as a treatment for muscular dystrophy.
-- Crystal Phend
Sniffing Out New Strategies to Treat Gliomas
Intranasal delivery of neural stem/progenitor cells resulted in rapid migration to experimental gliomas, increasing to 24% of cells in the dose administered within 24 hours, an international group of investigators reported.
Within 6 hours after administration via nose drops, evidence of stem cell enrichment appeared in tumors implanted in mice, as shown by MRI evaluation. The results were consistent with three different glioma cell lines.
Researchers observed minimal evidence of migration to adjacent, nontumor tissue and no evidence of localization to the periphery, as reported in the December issue of Stem Cells Translational Medicine.
"Our study provides proof-of-concept that the noninvasive intranasal passage of neural stem/progenitor cells is a highly attractive and efficient alternative method of cell administration for stem cell-based therapies in brain tumors," Nils Ole Schmidt, MD, of University Medical Center Hamburg-Eppendorf in Hamburg, Germany, and co-authors wrote of their findings. "This offers the possibility of multiple treatments, potentially with different therapeutic payloads, during the disease course."
The studies also revealed two major routes of cell migration: the olfactory nerve pathways and the microvasculature of the nasal mucosa. Researchers also believe they have identified a potential chemotactic signal that draws the cells toward the tumor.
-- Charles Bankhead