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Using gene therapy to create long-lasting production of antibodies to nicotine, blocking its physiological effects, passed an initial test in mice. Also this week: saving the spine through diet.
Nicotine Vax Effective in Mice
A gene therapy approach that induces anti-nicotine antibody production blocked nicotine's physiological effects in mice, according to a report in Science Translational Medicine from researchers led by Ronald Crystal, MD, of Weill Cornell Medical College in New York City.
Previous anti-nicotine vaccines have failed, largely because they didn't produce a lasting effect. To overcome that, Crystal and colleagues inserted the genetic sequence of a nicotine antibody into an adenovirus vector aimed at liver cells. In culture, the infected cells cheerfully began pumping out the antibody.
In mice treated with the vaccine and then given an injection of nicotine, the antibodies circulating in the blood gobbled up the drug before it could get to the brain. Specifically, nicotine concentrations in their brains were only 15% of the levels in untreated mice. What's more, the treated mice had none of the physiological effects of nicotine, such as lowered heart rate and blood pressure.
The vaccine appeared safe and long-lasting, but the researchers cautioned it will need more testing before it's ready for human trials.
-- Michael Smith
Saving the Spine Through Diet
Chronic spinal compression caused by secondary damage to the spinal cord or disks following an injury may respond to oral omega-3 fatty acids and curcumin, suggested researchers from the University of California Los Angeles.
To explore the potential anti-inflammatory effects of docosahexaenoic acid (DHA) and curcumin, a component of the curry spice turmeric, Langston Holly, MD, and his group induced delayed spinal injury in a group of rats. The animals were then fed a Western-style diet, high in fats and carbohydrates, or a diet enriched with the anti-inflammatory factors.
Animals given the therapeutic diet were able to maintain their gait function despite the delayed injury, while those fed the Western diet developed serious mobility problems. Molecular analysis revealed that the likely protective factors induced by the diet included brain-derived neurotrophic factor and syntaxin-3.
"We have demonstrated that DHA and curcumin can counteract the effects of chronic spinal cord compression through several molecular mechanisms, resulting in the preservation of neurological function," Holly and colleagues wrote in the Journal of Neurosurgery: Spine.
-- Nancy Walsh
Dampening Flu Infection
Researchers have discovered a gene that might represent a new therapeutic target for influenza A viruses.
The PA polymerase gene in the flu virus produces a protein called PA-X when a ribosomal frame shift occurs. Paul Digard, of the University of Edinburgh in Scotland, and colleagues found that, when the protein is created, it helps control the host's response to influenza A infection.
Studies in mice using the fully reconstructed virus that caused the Spanish flu pandemic of 1918 found that the animals recovered from the infection when PA-X was present. When PA-X was not present, however, there was an exaggerated immune response, making the infection worse.
"Loss of PA-X expression leads to changes in the kinetics of the global host response, which notably includes increases in inflammatory, apoptotic, and T-lymphocyte signaling pathways," the researchers wrote in Science.
"Thus, we have identified a previously unknown influenza A virus protein that modulates the host response to infection, a finding with important implications for understanding influenza A virus pathogenesis."
-- Todd Neale
Virus May Boost Bone Recovery
Rapid repair of a broken bone or accelerated healing around a joint replacement may be possible with a re-engineered plant virus, researchers reported in Molecular Pharmaceutics.
Plant viruses can't infect people, so they can serve as a low-risk platform for all kinds of genetic manipulations -- in this case altering an external protein on the tobacco mosaic virus to express factors that encourage stem cells to differentiate into bone.
In the laboratory, stem cells cultured on surfaces coated with the modified virus formed bone nodules within 2 days versus 2 weeks otherwise. There was also an uptick in markers of bone formation, such as bone morphogenetic protein-2 (BMP-2) and osteocalcin.
"What we've seen could prove very useful, particularly when it comes to external implants in bones," lead author Qian Wang, PhD, of the University of South Carolina in Columbia, said in a press release. "If our results can be further developed ... you might be able to use different kinds of nanoscale patterning on the titanium surface to create all kinds of different cellular responses."
-- Crystal Phend
Healing Response to MI May Actually Harm Heart
The reason why heart attack sufferers are at risk for a recurrent infarction could be due to an inflammatory cascade set in motion to heal the damaged myocardium, suggested Matthias Nahrendorf, MD, PhD, of the Massachusetts General Hospital in Boston, and colleagues.
In mice with induced MIs, researchers found increased activity -- away from the culprit lesion -- of an enzyme that breaks down the fibrous plaque cap, as well as an increase of monocytes and other inflammatory immune cells in those atherosclerotic plaques.
They also found an increased amount of monocytes in the mice's spleens, but, in splenectomized mice, the atherosclerosis did not advance.
"We identified an increased supply of innate immune cells as a driving force for this phenomenon," they wrote online in Nature and suggested that "interrupting the monocyte supply chain" would reduce the risk of recurrent MI.
-- Chris Kaiser
DBS Fends Off Urge to Binge
Deep brain stimulation suppressed binge eating in a preclinical model, an effect that was largely reversed by a drug that binds to dopamine receptors, according to a study reported at ENDO 2012 in Houston.
Following implantation of a bipolar electrode in the nucleus accumbens, mice were allowed to feed freely on a high-fat food for an hour each day. Binges were defined as consuming 25% or more of daily calories during the one-hour session.
When deep brain stimulation was activated, mice with the brain implants ate significantly less that did control mice without the implants (P<0.05). The stimulation appeared to have a carry-over effect, as the implanted mice also ate less than the control mice on days when they did not receive deep-brain stimulation.
Pretreatment with the dopamine receptor antagonist raclopride inhibited the effect of brain stimulation on binge eating by more than 50%, adding to evidence that altered dopaminergic transmission in the nucleus accumbens plays a role in binge-eating disorder, reported Casey Halpern, MD, of the University of Pennsylvania in Philadelphia.
-- Charles Bankhead
Exercise Cuts Amyloid Blobs
Exercise was more effective than diet control in preventing beta-amyloid plaque formation in an animal model of Alzheimer's disease, a study published in the Journal of Biological Chemistry found.
The research team, led by Ayae Kinoshita, PhD, of Kyoto University in Japan, simulated Alzheimer's disease in mice by feeding them a high-fat diet and randomized them to diet control, exercise, or both. Memory was tested in a maze study, with results measured against control rats fed a standard diet.
"Accumulating evidence suggests that some dietary patterns, specifically high fat diet, increase the risk of developing sporadic Alzheimer's disease," they wrote.
Mice in the exercise group had a greater reduction in beta-amyloid formation and better memory than those in the diet control group. There was no significant difference in those measures in the exercise group compared with the combined interventions.
"Therefore, our results clearly supported that exercise reduced oligomeric [beta-amyloid] levels after onset of [beta-amyloid] deposition, even if the mice were fed with high fat diets," the researchers wrote.
-- Cole Petrochko
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