A new type of gene therapy could transform the diagnosis and treatment of Alzheimer’s disease, according to a new study. Researchers at St. Jude Children’s Hospital have discovered that a particular enzyme can be used to regulate so-called plaque buildup in the brains of lab mice afflicted with a mouse model of the disease. The findings could represent an important step towards halting and reversing the neurodegenerative disorder that currently affects upwards of five million Americans.
Several hallmark symptoms of Alzheimer’s disease are associated with the slow accumulation of a set of extracellular proteins in the brain. These superfluous proteins, known as plaques, accrue between nerve cells in the brain’s gray matter. As a result, a range of cognitive and emotional functions begin to deteriorate.
The new study, which is published in the journal Nature Communications, sought to determine whether this buildup can be influenced by the enzyme neuraminidase 1 (NEU1) – a complex protein responsible for an array of cellular housekeeping, including the recycling of unneeded proteins. According to senior author Alessandra d’Azzo, a trial involving mice yielded promising results. "The findings suggest that down-regulation of NEU1 and a reduced supply of the enzyme may contribute to the development of Alzheimer's disease or similar neurodegenerative disorders in some patients," she said in a press release. "Among the questions we are asking is whether a therapeutic window exists when the enzyme could be used to halt or even reverse the disease."
The team found that, in mice afflicted with a type of neurodegeneration similar to Alzheimer’s disease, plaque buildup declined dramatically after a few weeks of gene therapy designed to boost NEU1 activity. The necessary genes were delivered to the subjects’ brains by way of a modified cold virus. “These results suggest that not only is NEU1 deficiency a risk factor for developing Alzheimer's disease, but that this enzyme could be used to slow or even reverse the disease process," d’Azzo explained.
According to the National Institutes of Health, neurodegenerative diseases currently affect millions of people worldwide. The conditions, which are characterize by a gradual loss of nerve functions, usually result in mental decline and an array of cognitive impairments. In turn, these symptoms often bring with them a number of lifestyle changes as well as an increased risk of injuries.
Source: Ida Annunziata, Annette Patterson, Danielle Helton, Huimin Hu, Simon Moshiach, Elida Gomero, Ralph Nixon, Alessandra d’Azzo. Lysosomal NEU1 deficiency affects amyloid precursor protein levels and amyloid-β secretion via deregulated lysosomal exocytosis. Nature Communications, 2013