Drug is supposed to defeat Alzheimer's

New drug against Alzheimer's, Parkinson's and prion diseases successfully tested in mice

11/10/2013

Diseases such as Alzheimer's, Parkinson's and CJD cause the death of nerve cells in the affected person's brain. The cause is a disease-related accumulation of proteins in the neurons. So far, there has been no drug and no therapy that could prevent those affected gradually lose more and more brain functions. Available medicines can only slow down the progression of the disease.

British researchers have now succeeded in developing a drug that will protect the brain cells of diseased mice in the long term. However, a cure for the diseases in humans is far from being found. Especially since the experimental animals suffered from serious side effects. However, according to experts, the study could usher in a turning point in the search for a drug for Alzheimer's disease, as further research yields positive results. The study was published in the journal „Science Translational Medicine“ released.

Active substance should prevent production stops of the proteins in the cells
Prof. Giovanna Mallucci from the University of Leicester in England and her colleagues examined how mice can be treated for a so-called prion disease. For this they developed together with the pharmaceutical company GlaxoSmithKline (GSK), which holds the patent for the drug, the active ingredient GSK2606416. The study was funded by the UK Medical Research Council, a government agency.

As it turned out, the drug protected the brain cells of the mice so that the neurons did not die off and no disease-specific symptoms were established in the rodents. The animals already suffered from disease symptoms, these were formed by the drug back. In addition to the positive effects but also showed side effects of the drug. The researchers recorded a slight increase in the blood sugar level of the mice and a weight loss of about 20 percent of the body weight on average.

Patients with a so-called prion disease such as Creutzfeldt-Jakob Disease (CJD) have a greater amount of prions - misfolded proteins - in the body, which, according to researchers, affects the overall protein balance of the affected cells. Since prions are identified by cell sensors as harmful substances, the affected cell reacts with a production stop of the proteins. As a result, the neurons die off as a result. The enzyme „Perk“ (Protein kinase RNA-like endoplasmatic reticulum kinase) is responsible for shutting down protein production. The researchers therefore use this enzyme in the mice to prevent the production of proteins from stopping. The aim was therefore not to prevent the accumulation of prions in the cells, which was often the research approach.

Pathogenic (pathogenic) prions usually enter the human body via contaminated food or they form as part of a spontaneous refolding of the body's own prions. In addition to CJD, BSE (mad cow disease) in cattle and Scarpie (scrapie) in sheep are also associated with a prion infection.

Active substance against prion diseases has side effects
In their study, Mallucci and her colleagues treated a test group of young mice seven weeks after infection with prions. At this stage, the disease had already spread in the brain but still causes no symptoms. The second experimental group was treated only nine weeks after infection with the drug. These mice already suffered from memory and behavioral disorders. The drug was administered orally to all rodents twice a day.

As the researchers report in the journal, all animals were virtually symptom-free after twelve weeks, with memory problems that had already persisted. The vital protein production had been re-stimulated by the drug, so the goal at „Perk“ to be successfully implemented. All control mice that were not treated with the drug had severe prion disease.

Although a small portion of the successfully treated mice should actually live longer to explore whether the drug also affects the lifespan of the animals, the researchers had to kill almost all experimental animals. The rodents had lost on average 20 percent of their body weight and therefore had to be killed according to animal regulations. This limit is intended to prevent unnecessary suffering from emaciated animals. Among the experimental animals were also older mice who received the drug for a period of seven weeks from the age of six months. In these rodents, no weight loss was recorded in contrast to the younger animals. All animals should despite weight loss „have been obviously fit and active, the researchers write.

Drug raises great hope for Alzheimer's research
It is not only in the case of prion diseases that non-functional proteins accumulate. Neurological or neurodegenerative diseases such as Alzheimer's and Parkinson's are also characterized by the protein-related death of neurons. Therefore, scientists hope that the new drug can also be used in these diseases. But first, a more in-depth, intensive research is necessary, before it is only necessary to test the agent in humans.

„What is really amazing about it is the discovery of a drug that completely prevents neurodegeneration for the first time. This remedy would not be applied to humans yet, but it means we can do it and it's a start“, Mallucci explained „BBC News“.

Because the enzyme „Perk“ Not only in neurons but throughout the body occurs, the drug has an effect virtually on the entire organism. So he also influenced the pancreas and thus the blood sugar level regulation of the mice.

Experts around the world are enthusiastic and reserved at the same time with regard to the applicability of the active substance to Alzheimer's and Parkinson's. „I suspect that this study will once count as the turning point in the search for a cure for Alzheimer's, "said Roger Morris of King's College London „BBC News“. „I am very excited because this is the first evidence in a living animal that you can delay neurodegeneration. The world will not change tomorrow, but this is a groundbreaking study. "(Ag)