By pressure-injecting the gene responsible for producing the specific protein – called amyloid-beta 42 – the researchers caused the mice to make antibodies and greatly reduce the protein’s build-up in the brain. Accumulation of amyloid-beta 42 in humans is a hallmark of Alzheimer’s disease.
"The whole point of the study is to determine whether the antibody is therapeutically effective as a means to inhibit the formation of amyloid-beta storage in the brain, and it is," said Dr. Roger Rosenberg, the study’s senior author and director of the Alzheimer’s Disease Center at UT Southwestern.
The gene injection avoids a serious side-effect that caused the cancellation of a previous multi-center human trial with amyloid-beta 42, researchers said. UT Southwestern did not participate in that trial. In that earlier study, people received injections of the protein itself and some developed dangerous brain inflammation.
The new study is available online and appears in an upcoming issue of the Journal of the Neurological Sciences.
The researchers used mutant mice with two defective human genes associated with Alzheimer’s, genes that produce amyloid-beta 42. "By seven months, the mice are storing abundant amounts of amyloid-beta 42," said Dr. Rosenberg, who holds the Abe (Brunky), Morris and William Zale Distinguished Chair in Neurology.
While the mice were young, the scientists coated microscopically small gold particles with human amyloid-beta 42 genes attached to other genes that program cells to make the protein. The particles were then injected with a gene gun into the skin cells of the mice’s ears using a blast of helium.
After receiving 11 injections over several months, the mice showed a high level of antibodies to amyloid-beta 42, and a 60 percent to 77.5 percent reduction of plaques in their brains.
As controls, the researchers also either injected mutant mice with the gene for a related but harmless protein, amyloid-beta 16, or with a gene vaccine that lacked any amyloid genes. These treatments did not cause antibody production, and the mice showed the large amounts of amyloid-beta 42 brain plaques normally seen in animals with these mutations.
The gene injection showed superior results compared to a previous human study in which amyloid-beta 42 protein itself was injected into muscle, Dr. Rosenberg said. That study was halted when a small percentage of participants developed inflammation of the brain and spinal cord.
Injecting the gene, in contrast, caused no brain inflammation in the mice.
Dr. Rosenberg said the difference was partly because in the human trial, the protein was injected along with a substance called an adjuvant, which increased the immune response to abnormal excessive levels, causing the dangerous brain inflammation. In addition, the immune response in humans may have involved antibodies called Th1, which were probably partly responsible for the inflammation. The gene injection in the mouse study produced Th2 antibodies, which have a low probability of causing brain inflammation. Furthermore, no adjuvant was needed for antibody production.
The gene immunization is now undergoing further animal studies, with the ultimate goal being a clinical trial in humans. The researchers also plan to see if it can reverse the size of established plaques in the brains of mice.
Aline McKenzie | EurekAlert!
Zap! Graphene is bad news for bacteria
23.05.2017 | Rice University
Discovery of an alga's 'dictionary of genes' could lead to advances in biofuels, medicine
23.05.2017 | University of California - Los Angeles
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
23.05.2017 | Event News
22.05.2017 | Event News
17.05.2017 | Event News
23.05.2017 | Life Sciences
23.05.2017 | Medical Engineering
23.05.2017 | Life Sciences