From the Labs: Biomedicine

Rejuvenating the Brain
Neurons transplanted from fetal animals make older brains act young

Source: “Cortical plasticity induced by inhibitory neuron transplantation”
Arturo Alvarez-Buylla, Michael P. Stryker, Sunil P. Gandhi, et al.
Science 327: 1145-1148.

Results: By transplanting fetal neurons into young mice, researchers induced the animals to rewire neural circuits in their visual system.

Why it matters: Rodents and other animals, including humans, experience a period of neural plasticity before the brain circuitry becomes fixed. Researchers hope to enhance this innate capacity in order to improve healing after brain injury and other neurological problems in adulthood. This study was the first to show that animals can be induced to undergo a second round of flexibility. Pinpointing the specific molecules that made it possible could inspire new treatments.

Methods: The researchers took neurons of a specific type, called inhibitory neurons, from the brains of fetal mice and grafted them into newborn or young mice. Then they gauged neural plasticity by measuring changes in the animals’ brains after they were blinded in one eye. The mice experienced the normal period of neural flexibility in the visual system at around 28 days. But a second period of plasticity occurred at around 35 days, when the visual circuitry is normally fixed. Its timing corresponded to the age of the transplanted cells, which suggests that the transplant triggered it.

Next steps: Researchers plan to isolate specific types of inhibitory neurons and transplant them in an attempt to find the specific cell type responsible.

Anti-Cancer RNA
RNA interference to tumor cells

Source: “Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles”
Mark E. Davis et al.
Nature 464: 1067-1070

Results: Researchers at Caltech used specialized nanoparticles to deliver a type of gene-silencing RNA to cancer cells in human subjects. Biopsies from three melanoma patients who had been given the therapy showed that the particles entered cancer cells but not healthy cells, and that the RNA successfully blocked the action of a cancer-related molecule that was its target.

Why it matters: Certain RNA molecules can cut messenger RNA and prevent it from producing proteins, a phenomenon known as RNA interference. But it has been difficult to deliver RNA-based therapies into the right cells. RNA injected into the bloodstream is typically filtered out by the kidneys before reaching its target, so the therapy has been limited to areas where the molecules can be delivered directly, such as the eyes or lungs. The new trial is the first to show that RNA can be ferried through the bloodstream in nanoparticles that protect the molecules and deliver them to cancer cells.

Methods: Researchers started with an RNA molecule designed to silence a gene used for DNA synthesis and repair. They enclosed the RNA in nanoparticles made of a sugar-based polymer, another polymer that binds weakly to water to enhance the particles’ stability, and a protein that is displayed on the particles’ exterior and binds with receptors on cancer cells, signaling the cells to absorb them. Once inside those cells, the nanoparticles release the RNA molecules to attack their targets.

Next steps: Researchers are studying patients with other tumors in an early-stage trial. They won’t be able to assess how effective the treatment is at shrinking tumors until testing it in more patients.