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!
Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences
Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.
Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...
16.03.2018 | Event News
13.03.2018 | Event News
08.03.2018 | Event News
16.03.2018 | Earth Sciences
16.03.2018 | Physics and Astronomy
16.03.2018 | Life Sciences