Researchers may be one step closer to finding the holy grail of potential Alzheimer's treatments – a single-dose vaccine that prevents the onset of the disease. A new study from the University of Texas Southwestern Medical Center has revealed a novel DNA vaccine has been shown to successfully reduce the accumulation of two toxic proteins associated with the progression of Alzheimer's disease.

Despite the growing array of alternative hypotheses attempting to explain the origins of Alzheimer's, the bulk of scientific research is still searching for ways to stop the development of two kinds of toxic proteins associated with the neurodegenerative symptoms seen in the disease: amyloid beta plaques and neurofibrillary tau tangles.

One of the more promising tactics to battle the disease has been to develop a vaccine that stimulates the body's immune response to attack the build-up of those toxic proteins. A vaccine targeting amyloid beta plaques in particular is not a new idea, but progress was quickly halted after a controversial human trial failed in the early 2000s. The Phase 2 trial was quickly terminated after a small number of participants developed meningoencephalitis, a type of dangerous brain swelling.

Since then, researchers have been cautiously working to develop safer, and more effective, forms of immunotherapy, designed to block the aggregation of these toxic proteins while avoiding the problematic autoimmune inflammation that struck down the earlier work. One approach, called passive immunization, works to produce antibodies in a laboratory environment that are then subsequently administered to patients. However, this is often an expensive and time-consuming option.

Roger Rosenberg, founding director of the Alzheimer's Disease Center at UT Southwestern, has been working for years on another approach, called active immunization. This process involves the more traditional method of administering a vaccine that stimulates the body's immune system to produce its own antibodies.

Rosenberg and his team have been working for well over a decade on the vaccine, and the idea targets the DNA coding for the toxic proteins. The concept of a DNA-based vaccine is still relatively new, however early investigations have shown the technique is potentially effective in inducing an immune response while avoiding negative autoimmune inflammation.

The latest study to be published for this new DNA vaccine reports the most positive results to date, revealing a significant reduction in both amyloid and tau levels in mouse models. The study reveals the vaccine does not induce negative inflammatory effects and, most excitingly, it is the first antibody or vaccine treatment to target both amyloid and tau pathologies at the same time.

A major innovation in the new research was the discovery that it seems to be much safer to administer the experimental DNA vaccine into superficial skin cells, instead of the more traditional intra-muscular injection. This alternative route of vaccination may be key to avoiding some of the more negative autoimmune responses seen in prior trials.

"This study is the culmination of a decade of research that has repeatedly demonstrated that this vaccine can effectively and safely target in animal models what we think may cause Alzheimer's disease," says Rosenberg. "I believe we're getting close to testing this therapy in people."

The research still faces some major hurdles as a large volume of prospective treatments aimed at targeting amyloid plaques have failed in clinical trials in recent years. Many researchers are beginning to suspect that treatments designed to target the build-up of these toxic proteins may only be effective if administered before they accumulate and cause damage. Rosenberg agrees, suggesting his vaccine may be most effective as a preventative agent before major symptoms appear.

"The longer you wait, the less effect it will probably have," says Rosenberg. "Once those plaques and tangles have formed, it may be too late."

The problem researchers now face is that we currently don't have any reliable or effective way to diagnose the onset of Alzheimer's at the very earliest stages, so it becomes incredibly difficult to construct trials that can test those most at-risk patients. The long gestation of the disease also means that any preventative agent being tested will need significant long-term follow up work before its efficacy can be proven. All this means that while there are many promising breakthroughs on the horizon in the field of Alzheimer's research, it could take 10 or 20 years before we know if the new treatments truly work.

The new research was published in the journal Alzheimer's Research & Therapy.

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