New drug against Alzheimer's, Parkinson's and prion diseases successfully tested in mice
Diseases such as Alzheimer's, Parkinson's and Creutzfeldt-Jakob disease (CJD) lead to the death of nerve cells in the brain of those affected. The cause is a disease-related accumulation of proteins in the neurons. To date, there has been no medication or therapy that could prevent people from gradually losing more brain functions. Available drugs can only slow the progression of the disease.
British researchers have now succeeded in developing an active ingredient that is intended to 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 severe side effects. According to experts, the study could nevertheless mark a turning point in the search for a drug for Alzheimer's, if further research delivers positive results. The study was published in the journal "Science Translational Medicine".
Active ingredient to prevent production of proteins in the cells from stopping Prof. Giovanna Mallucci from the University of Leicester in England and her colleagues investigated how mice can be treated for a so-called prion disease. For this purpose, they developed the active ingredient GSK2606416 together with the pharmaceutical company GlaxoSmithKline (GSK), which holds the patent for the drug. The study was funded by the British Medical Research Council, a government agency.
As it turned out, the active ingredient protected the brain cells of the mice so that the neurons did not die and no disease-specific symptoms appeared in the rodents. If the animals already suffered from illnesses, the medication partially resolved them. In addition to the positive effects, there were also side effects of the active ingredient. The researchers recorded a slight increase in the blood sugar level of the mice and a weight loss of around 20 percent on average.
Patients with a so-called prion disease such as Creutzfeldt-Jakob disease (CJK) have a larger amount of prions - incorrectly folded proteins - in the body, which, according to researchers, affects the entire protein balance of the affected cells. Since prions are identified as harmful substances by cell sensors, the affected cell responds by stopping the production of the proteins. As a result, the neurons die. The enzyme "Perk" (protein kinase RNA-like endoplasmatic reticulum kinase) is responsible for shutting down protein production. The researchers therefore started using this enzyme in mice to prevent the proteins from stopping production. The aim was therefore not to prevent the accumulation of prions in the cells, which has often been the research approach up to now.
Pathogenic (disease-causing) prions usually get into the human body via contaminated food or they form during the spontaneous refolding of the body's own prions. In addition to CJK, BSE (mad cow disease) in cattle and scarpie (scrapie) in sheep are related to a prion infection.
Active substance against prion diseases has side effects As part of 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 to the brain but had not yet caused any symptoms. The second experimental group was only treated with the active substance nine weeks after infection. 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 specialist magazine, all animals were virtually symptom-free after twelve weeks, although memory problems that had already occurred still persisted. The vital protein production was stimulated again by the active ingredient, so that the goal of "Perk" could be successfully implemented. All mice in a control group who were not treated with the active ingredient became seriously ill with the prion disease.
Although a small proportion of the successfully treated mice were supposed to live longer in order to investigate whether the active ingredient also has an impact on the lifespan of the animals, the researchers had to kill almost all experimental animals. The rodents had lost an average of 20 percent of their body weight and had to be killed in accordance with the animal regulations. This limit is intended to prevent unnecessary suffering from emaciated animals. Among the experimental animals were older mice that received the active substance for seven weeks from the age of six months. In contrast to the younger animals, these rodents showed no weight loss. Despite the weight loss, all animals are said to have been "obviously fit and active", the researchers write.
Active ingredient raises great hope for Alzheimer's research It is not only in prion diseases that non-functional proteins accumulate. Neurological and neurodegenerative diseases such as Alzheimer's and Parkinson's are also characterized by the protein-related death of neurons. Scientists therefore hope that the new active ingredient can also be used for these diseases. But first of all, further, intensive research is necessary before all that can be thought of is testing the drug on humans.
“What is really surprising about this is the discovery of a preparation that for the first time completely prevents neurodegeneration. This would not be used on humans yet, but it means that we can do it and it is a start, ”Mallucci told BBC News.
Since the enzyme "Perk" occurs not only in neurons but in the whole body, the active ingredient has an effect on the whole organism. He also influenced the pancreas and thus the blood sugar level regulation of the mice.
Experts worldwide are enthusiastic and at the same time reluctant to use the active ingredient in Alzheimer's and Parkinson's. "I suspect that this study will one day be seen as the turning point in the search for an anti-Alzheimer drug," said Roger Morris of King's College London to BBC News. "I am very excited because it is the first evidence in a living Animal is that you can delay neurodegeneration, so the world won't change tomorrow, but it's a groundbreaking study. " (ag)
Image: Viktor Mildenberger / pixelio.de