Winners 2011
Contact persons
Dr. Petra Burgstaller
Co-Lead Venture Creation & MAxL
Christina Enke-Stolle
Co-Lead Venture Creation & MAxL
Those were the 2011 m4 Award winners!
Dr. Felix Hausch
Dr. Marcelo Paez-Pereda
Max Planck Institute of Psychiatry, Munich
FLipeD: FKBP51 Ligands for Personalized Depression Therapy
The body’s own stress hormones, such as cortisol, play an important role in the development of depression. For example, approximately 50% of all patients with depression exhibit an altered hormonal stress response, which is attributable to a reduced response to cortisol. The protein FKBP51 is a key regulator in mediating the stress response. It determines how effectively cortisol acts in the body. It has been demonstrated that reducing FKBP51 can lead to a normalization of the hormonal stress response and an improvement in depression symptoms. Dr. Hausch and his team are leveraging their knowledge of the atomic structure of the FKBP51 protein to design new active compounds that inhibit this protein. These compounds would be specifically targeted for patients who suffer from a reduced response to cortisol. Since this therapeutic approach differs mechanistically from existing antidepressants, newly developed drugs could be particularly well-suited for use in combination therapy for depression.
Prof. Dr. Karl-Peter Hopfner
Gene Center of the Ludwig-Maximilians Universität München
Priv.-Doz. Dr. Dr. Fuat Oduncu, MBA
Medical Clinic Downtown, Munich
Prof. Dr. Georg H. Fey
Friedrich-Alexander-University Erlangen-Nürnberg
Personalized Leukemia Therapy Through “Dual Targeting” with Antibody Derivatives (Triplebodies)
Acute myeloid leukemia (AML) is a type of blood cancer. There are many different subtypes of AML, most of which are very difficult to treat: only 16%–27% of patients survive longer than four years. The reason for this is that minimal residual disease remains after conventional chemotherapy. New cancer cells form from the surviving AML stem cells, leading to relapses. The team led by Prof. Dr. Karl-Peter Hopfner, PD Dr. Dr. Fuat Oduncu, and Prof. Dr. Georg Fey is developing a special type of antibody, known as “triplebodies,” which bind to two surface molecules on cancer stem cells. At the same time, the triplebodies bind to the immune system’s natural killer cells, thereby directing them to the cancer cells and effectively killing them. The identification of two surface molecules on cancer cells and cancer stem cells enables the development of a personalized AML therapy better tailored to specific patient groups. The triplebodies are also of interest as a platform technology, as this mechanism of action could, in principle, also be used to treat other diseases.
Prof. Dr. Oliver Ritter
Dr. Martin Czolbe
University Hospital Würzburg, Department of Internal Medicine I
Blocking the Calcineurin-Importin Interaction as an Innovative New Mechanism of Action for the Treatment of Heart Failure
Heart failure manifests as reduced exercise tolerance, severe shortness of breath, and high mortality. The enzyme calcineurin plays a key role in the development of heart failure; in cases of heart failure, it is taken up by the cell nucleus of cardiac muscle cells and then triggers a signaling cascade within the nucleus that leads to the activation of misregulated genes. To be taken up into the cell nucleus, calcineurin requires a carrier protein, known as an importin. Prof. Ritter’s research group was able to identify this importin, which is suitable as a target molecule for a novel therapy for heart failure. They have also succeeded in developing a peptide drug that prevents the uptake of calcineurin into the cell nucleus and inhibits the signaling pathway. As part of the funding provided by the m4 Award, the toxicological and pharmaceutical properties of this peptide drug candidate will be investigated, and preparations for clinical trials will be made. Compared to current treatments for heart failure, the proposed drug would have the advantage of acting very early in the disease mechanism and could thus prevent the progression of the disease.
Prof. Dr. Dolores Schendel
Dr. Christiane Geiger
Dr. Miran Javorović
Helmholtz Munich, Institute for Molecular Immunology
Personalized Dendritic Cells as Vaccines for Patients with Hormone-Resistant Prostate Cancer
Prostate cancer is the most common cancer in men and has a high mortality rate. After 2–3 years, many metastatic tumors develop resistance to standard hormone therapy and become difficult to treat. Prof. Dr. Dolores Schendel’s research group aims to enable the body’s own immune system to recognize and destroy cancer cells. Cells of the immune system, known as dendritic cells, serve as a therapeutic vaccine. These cells present fragments of surface molecules found on tumor cells to the immune system, thereby enabling the body to recognize the tumor cells as “foreign.” This triggers a broad immune response and could lead to a complete cure. The cell therapy platform technology developed in this project represents an innovative and promising field of medicine that could also be extended to other indications.
Dr. Joel Schick1
Dr. Marcus Conrad1,2
Prof. Dr. Wolfgang Wurst1
1Helmholtz Zentrum Munich, Institute of Developmental Genetics,
2DZNE – German Center for Neurodegenerative Diseases
RỌScue: New Drugs to Combat Neurodegenerative Diseases
In an aging society, the need for drugs to treat neurodegenerative diseases such as Alzheimer’s or Parkinson’s will continue to grow. It has long been known that the death of neurons is caused by reactive oxygen species (“radicals”). What is new, however, is the realization that these substances often trigger cell death via specific signaling pathways. The proteins involved in these signaling pathways therefore offer a new target for drugs. The team led by Dr. Joel Schick and Dr. Marcus Conrad has developed a novel testing system to evaluate the protective effects of drug candidates: They use cells that lack certain genes and consequently produce particularly high levels of reactive oxygen species. The cells will die unless the signaling cascades leading to their death are inhibited by a drug candidate. Using a semi-automated robotic system and automated assessment of cell viability, large numbers of drug candidates can be tested very quickly. The most promising candidates will then be validated in animal studies and further developed into neuroprotective drugs.