Picture: In a mouse model of Parkinson’s disease, animals treated with anle138b were found to form significantly fewer synuclein aggregates (stained in brown) than did controls that received a placebo.
© Giese, LMU Munich
Neurodegenerative diseases are diseases of the nervous system that often progress slowly and are characterized by a loss of mental and physical abilities. The deposition of disease-relevant accumulations of protein in the brain plays an important role in the pathogenesis of many neurodegenerative diseases. Scientists at the LMU and the Max Planck Institute (MPI) for Biophysical Chemistry in Göttingen have successfully developed a drug candidate that can significantly reduce the formation of these deposits. In the joint spin-off company MODAG GmbH the active substance anle138b is now to be developed up to market maturity to stop diseases such Parkinson’s, Alzheimer’s and Creutzfeld-Jakob in the future. To this effect, MODAG successfully concluded its first round of financing with up to EUR 8 million in participation with the Bayerische Patentallianz GmbH representing the two research institutions LMU and MPG.
Often neurodegenerative diseases are a result of protein deposits, which can damage nerve cells. In the case of Parkinson’s, deposits of aggregated synuclein proteins become visible in the brain when viewed under the microscope. Precursors of these deposits, the oligomers, are highly neurotoxic. For humans, this can result in muscle tremors, movement disorders and muscular rigidity. Also wit the Creutzfeld-Jakob disease these disease-causing protein deposits, which are caused by so called prion proteins, are found. Both Professor Dr. Armin Giese, research group leader at the Center for Neuropathology and Prion Research at LMU Munich and Professor Dr. Christian Griesinger, Director at the Max Planck Institute for Biophysical Chemistry, Department of NMR-based Structural Biology in conjunction with their staff have developed a drug candidate that has prevented the formation of the toxic oligomeric forms of protein in tests with mice having Parkinson’s, thereby delaying the progression of neuronal damage to an extent previously unattained and thus prolonging the disease-free phase. A new feature is that the active substance called anle138b targets directly and specifically oligomer forms of protein. Thus, anle138b prevents the aggregation and formation of new, disease-relevant oligomer protein forms. The synthesized drug, which was administered with food to test mice, is tolerated very well in therapeutic doses and effectively penetrates the blood-brain barrier, thereby reaching high levels in the brain with a small dosage. The mice exposed to anle138b had significantly longer survival times and were able to display better motor coordination than their untreated sick siblings, as the results of the pre-clinical study impressively show.
In the future, diseases such as Parkinson’s could possibly be slowed down or even stopped with anle138b as disease-related processes are directly inhibited. However, the new substance is not only effective for diseases such as Parkinson’s. Positive research results show that anle138b is effective with Creutzfeld-Jakob by effectively inhibiting the aggregation of pathogenic protein deposits, and treated mice survive significantly longer. Likewise, the results in mouse models for Alzheimer’s are encouraging. Managing Director Dr. Torsten Matthias, also founder and CEO of AESKU.DIAGNOSTICS says that “due to the study results so far, the MODAG GmbH seriously gives me hope that with this new substance we will be able to offer the much-needed help for Parkinson’s and Alzheimer’s patients with an early stage and safe therapy.”
The underlying basic technology was patented as joint invention of the LMU München and the MPI for Biophysical Chemistry and was exclusively licensed by MODAG GmbH. “We are pleased that we could help bundling the research competencies of the Ludwig-Maximilians-Universität München and the Max Planck Institute for Biophysical Chemistry in the field of drug research in a targeted way into this promising spin-off company,” says Peer Biskup, Managing Director of the Bayerische Patentallianz GmbH, the patent marketing agency of the Bavarian universities and universities of applied sciences. “In addition to outstanding research skills, MODAG also has necessary development skills and extensive business know-how,” adds Astrid Giegold, Start-up & Portfolio Manager at Max Planck Innovation, MPG’s technology transfer organization.