Exploiting new biology concepts
neurodegenerative disease, & diabetes
Innate Repair (iR) scientists discovered a new molecular mechanism that is involved in regeneration and cancer progression, and named it, the Hes3 Signaling Axis, after two key components. The Hes3 Signaling Axis is generally turned off in tissues. However, when damage is inflicted, it is activated and drives regeneration. This basic phenomenon has powerful consequences in neurodegenerative disease, diabetes, and oncology:
Neurodegenerative disease: Damage to the brain leads to the activation of the Hes3 Signaling Axis in resident (endogenous) neural stem cells (NSCs). The activated NSCs proliferate and produce factors that help neurons survive the damage. In preclinical models of neurodegenerative disease and ischemic stroke, this leads to powerful benefits.
Diabetes: When the endocrine pancreas (the part of the pancreas responsible for the production of insulin) is damaged, the Hes3 Signaling Axis is activated in local resident cells and helps them better survive the damage, and then regenerate the damaged endocrine pancreas. In preclinical models where the Hes3 Signaling Axis is dysfunctional, the damage is more severe, regeneration is impaired, and diabetes kick in faster.
Oncology: Tumors are aberrant tissues that have a resident stem cell population (Cancer Stem Cells) and can regenerate following damage (often caused by the anti-cancer treatments). It is no surprise, then, that the Hes3 Signaling Axis is also activated in tumors such as the aggressive brain cancer glioblastoma. It appears that the Hes3 Signaling Axis provides a mechanism for some cancer cells to evade current therapies and keep on growing and regenerating the tumor: Normally, many cancer cells grow using more traditionally studied molecular mechanisms and drugs are delivered that block them. Some cancer cells stop growing or even die; but some can switch to using the Hes3 Signaling Axis and keep on growing. It is, therefore, essential to figure out how to block the Hes3 Signaling Axis and develop treatments against it.
iR is doing exactly that: We are working to validate the efficacy of our treatments and to identify new ones to develop for the clinic. Our initial focus is on brain cancer and we are pursuing that work in the UK. We are now starting the diabetes R&D program which we will pursue in Dresden, Germany. At the same time, we are planning the neurodegenerative disease program as well.
iR is registered in the UK and iR-Saxony is currently being established in Dresden, Germany.
Innate Repair - Saxony
We are excited to establish Innate Repair Saxony GmbH, the Germany chapter of Innate Repair, in Dresden, with the support of the city of Dresden innovation office, the Technische Universitaet Dresden and its corporate arm, TUDAG, and the transCampus® initiative. In this way, we will take full advantage of the vast basic and clinical expertise at the University and other institutions on campus, academic and business networks in Dresden and Saxony, and delve deeper into our collaborations with many Dresden scientists, in a city with a strong business innovation focus.
In Dresden, our initial focus will be on diabetes, a group of metabolic disorders that affects many people around the world. Our past research has demonstrated the involvement of the Hes3 Signaling Axis in many aspects of diabetes, including the growth of the insulin-producing cells of the endocrine pancreas, insulin production and release, protection of the pancreas from injury and regeneration following injury (see section "Selected Publications" for more information). We also demonstrated how insulin regulates the Hes3 Signaling Axis in the brain and specifically in resident neural stem cells that are important for the protection of injured neurons and the repair of the damaged tissue. Therefore, our underlying science provides multiple opportunities to explore and identify treatment candidates that will help with many aspects of the disease.
Team and Advisors
The TU Dresden is a public research university. It ranks among the best universities of engineering and technology in Germany. It is a member of TU9, a consortium of the nine leading German Institutes of Technology and one of eleven German universities with the title "University of Excellence".
Stefan R. Bornstein
Stefan is the Director of the Centre for Internal Medicine and the Medical Clinic and Policlinic III at the University Hospital Carl Gustav Carus of the Technical University of Dresden as well as the medical faculty’s Vice Dean of International Affairs and Development and a member of the supervisory board of the University Hospital of Dresden. Furthermore, he is Chair and Honorary Consultant for Diabetes and Endocrinology at King's College London.
Andrew V. Schally
Andrew is an Endocrine Oncologist and Distinguished Medical Research Scientist of the US Veteran Affairs Department, as well as Professor of Pathology, Professor of Medicine, Division of Oncology, and Endocrinology at the University of Miami. He is a recipient of the Nobel prize in Physiology or Medicine.
Gregor will be responsible for the operation of iRSN. He studied biology in Cologne. As staff scientist of a spin-off from the Heinrich Heine University Düsseldorf he was awarded his PhD in gene therapy. For six years he worked as group leader at the Carl Gustav Carus Faculty of Medicine of the TU Dresden. As a GWT-GmbH senior consultant he has been the head of the Grant Writing Office of the Department of Internal Medicine at the University Hospital Carl Gustav Carus since 2009. In 2020 he became the COO of the transCelerator program, funded by the Excellence Initiative "TUD 2028 - Synergy and beyond" of TU Dresden.
George P. Chrousos
George is Professor of Pediatrics and Endocrinology, Chairman, First Dept. of Pediatrics, National and Kapodistrian University of Athens. He holds a UNESCO Chair, has received numerous international awards and is a member of the US National Academy of Medicine (Institute of Medicine).
Deric M. Park
Deric M. Park, MD, FACP is Associate Professor of Neurology at the University of Chicago, Director of Medical Neuro-Oncology, and a faculty member of the Committee on Clinical Pharmacology and Pharmacogenomics. He is committed to identifying more effective therapies for patients suffering from brain-spine tumors.
Steven W. Poser
Steven received his Ph.D. from the University of Washington in Neurobiology. In both industry and academic laboratories, he successfully designed and implemented signal transduction and cell characterization studies in cancer, stem cell, and primary neuronal culture systems. These became an integral part of cell-based product development and drug discovery programs as well as resulted in numerous publications.
Significance: Neural stem cells operate the newly discovered Hes3 signaling pathway. Activation of this pathway leads to functional recovery in models of ischemic stroke.
Journal: Cold Spring Harbor Symposia on Quantitative Biology
Significance: Activation of the the Hes3 pathway by insulin in models of Parkinson's disease promotes functional recovery.
Journal: Proceedings of the National Academy of Sciences
Significance: Activation of the the Hes3 pathway in a manner that protects unwanted effects on blood vessels in models of Parkinson's disease promotes functional recovery.
Journal: Scientific Reports
Significance: The Hes3 pathway controls cultured cancer stem cells from different patients. Blocking the pathway by RNA interference (target: Hes3) kills those cells.
Journal: Journal of Biological Chemistry
Significance: The Hes3 pathway protects pancreatic islet cells during injury and regulates insulin production with powerful consequences in models of type 1 diabetes.
Significance: The Hes3 pathway promotes pancreatic regeneration after injury with powerful consequences in models of type 1 diabetes.
Journal: Scientific Reports
Significance: Pancreatic damage, high fat diet, and metformin administration regulate the Hes3 pathway in the brain, providing a new molecular mechanism by which metabolic dysfunction affects the brain.
Journal: FASEB J
Significance: Some cells in aggressive brain cancers can evade current therapies by switching from the standard molecular mechanisms that regulate their growth and survival to an alternative one. In this way, they become resistant to therapies that target the standard molecular mechanism. Knowing this ability allowed us to define the alternative mechanism and to identify treatments that target the cells that use it. Simply put, we discovered an escape route that cancer cells use to evade therapy and then we found drugs that block it.
Innate Repair is registered in London, UK.
Innate Repair Saxony is in the process of registering in Germany.
Dr. Gregor Mueller
Haus 27 (DINZ)
1. OG, Zimmer 1.642
Medizinische Klinik und Poliklinik III
und Zentrum für Innere Medizin,
Universitätsklinikum Carl Gustav Carus an der TU Dresden,
Fetscherstraße 74, 01307 Dresden, Germany
Tel.: +49 (0)351 458 2931
We follow the RCUK Common Principles on Data Policy