Potential Treatment Prototype for Taupathies and Neurodegenerative Brain Diseases Under Development

Potential Treatment Prototype for Taupathies and Neurodegenerative Brain Diseases Under Development

Researchers at the German Center for Neurodegenerative Diseases (DZNE) in Bonn have tested a new substance that may lead to a prototype for the development of drugs to treat Alzheimer’s disease and other tauopathies, including Huntington’s disease. The substance, anle138b, improved symptoms in mice and showed an improvement in their cognition, as reported in their publication entitled “Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies” published in the journal Acta Neuropathologica.

“We have found that this substance prevents the aggregation of tau proteins. This aggregation is typical of Alzheimer’s and other brain diseases classified as tauopathies,” explained DZNE investigator, Dr. Martin Fuhrmann, who worked on this study with colleagues at the Ludwig-Maximilians-University Munich (LMU) and the Max Planck Institute for Biophysical Chemistry (MPG) in Göttingen. “Treatment with anle138b could be one way of intervening in the progress of the disease.”

Like Huntington’s, in Alzheimer’s disease, tau proteins change: they detach from microtubules and gather into filamentous tau-tangles, resulting in impaired microtubule function and cell metabolism, eventually leading to neuronal death. Normally, tau proteins would stabilize the microtubules that integrate the cytoskeleton in brain neurons, a structure that works as a transport network for substances crucial to cell’s metabolism. “The experiments were inspired by our earlier studies that showed high efficacy against the formation of pathological protein aggregation,” claims Prof. Armin Giese, researcher at the Center for Neuropathology and Prion Research at the LMU Munich. “These led us to suspect that anle138b could prevent the aggregation of tau proteins.”

In this study, mice had a genetic deficiency that made them display several symptoms typically associated with tauopathies — the same as those seen in humans. Along with the concentration of tau proteins, symptoms included cognitive disorders and a shorter life expectancy. The team concluded that the anle138b substance when added to mice food works not only at a molecular level but alleviates the disease’s symptoms as well. “Mice working memory skills improved and they lived longer,” said Fuhrmann. The study also found mice suffered from less neuronal loss than those who had not received treatment.

“In contrast to other substances Anle138b is orally available because of its chemical and metabolic characteristics. Therefore, it stays for hours within the body and targets specifically protein aggregation,” explained Prof. Christian Griesinger from the Max Planck Institute for Biophysical Chemistry, whose team was responsible for synthesizing the substance. “Anle138b cannot stop the disease from progressing in the animal model, but it seems to slow it down,” reports Fuhrmann. “Anle138b is therefore a possible starting point for the development of drugs that prevent the aggregation of tau proteins.”

Nonetheless, the study notes that the results are not directly transferable to human patients just yet. “The efficacy and tolerance for humans have to be tested in demanding clinical trials. Even with an optimistic perspective it will take years until a treatment for patients might be available.” LMU and MPG are currently developing anle138b further in a joint research trial.

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