Cushing´s disease (CD) is a rare hormone condition caused by a tumor in the pituitary gland in the brain. Patients suffering from CD are severely impaired in their life quality and the only successful treatment up to now is pituitary surgery or administration of drugs with severe side effects. Scientists of the Max Planck Institute of Psychiatry around Günter Stalla and Marcelo Paez-Pereda, and the Helmholtz Zentrum München have discovered that Silibinin, a drug used for the treatment of toxic liver damage and mushroom poisoning with an outstanding safety profile in humans, which allows effective treatment of patients without any serious side effects, could be used in CD.
The pituitary tumor causing CD releases increased amounts of the stress hormone ACTH (adrenocorticotropin) leading to a cortisol release with major consequences. CD patients suffer from rapid weight gain, elevated blood pressure and muscular weakness. Furthermore, they are prone to osteoporosis and infections and may show cognitive dysfunction or depression. This knowledge was used as a starting point for further investigation. The researchers aimed to find a mechanism causing this process and a way to stop it. In the course of their research they found tremendously high amounts of HSP90 in the tumor tissue of patients. This heat shock protein helps to correctly fold the glucocorticoid receptor, another protein which in turn inhibits the production of ACTH. As a result, the large number of HSP90 molecules stick to the glucocorticoid receptor, preventing it from releasing its active structure and deploying its biological functions. In a further step the researchers found that a well known active principle called Silibinin binds to the C-terminus of HSP90 protein thus allowing glucocorticoid receptor molecules to detach from HSP90. After Silibinin treatment, tumor cells resumed normal ACTH production, tumor growth slowed down and symptoms of CD disappeared. Using Silibinin, a plant extract from milk thistle seeds, as a HSP90 inhibitor, the researchers discovered a non-invasive treatment strategy for Cushing´s disease which was also published in the journal Nature Medicine (Volume 21, number 3, March 2015). In 2013, the Max Planck scientists together with the technology transfer organization Max Planck Innovation filed a patent, which has been granted in the US and is pending in the EU, covering chemical and natural compounds, including Silibinin, to treat pituitary tumors as further medical use.
IBI has developed a highly concentrated and purified form of Silibinin. The company with 100 years of history in the pharmaceutical field now plans to perform clinical trials in a consortium with experienced scientists in this area and to rapidly access the market in order to enable the treatment of this rare and severe disease.
“IBI is a great match for the new technology from the Max Planck Institute of Psychiatry. The company has longstanding experience in the development of new therapeutic applications and can boast a worldwide production and marketing network. Furthermore, IBI is experienced in bringing innovative products into the clinic making it a strong partner for the development of a new and non-invasive treatment option for CD patients. We are pleased to have IBI as a partner to improve the treatment of patients suffering from this rare disease”, says Doris Maugg, patent and licensing manager at Max Planck Innovation.
IBI Istituto Biochimico Italiano G. Lorenzini S.p.A. is an Italian pharmaceutical company with global reach and 100 years of experience. It has a consolidated leadership in sterile penicillin market and a strong expertise in development and manufacturing of biopharmaceuticals products. IBI has a robust portfolio of products for export and is certified by FDA, AIFA, EDQM, and TGA.
Development and GMP manufacturing of parenteral formulation is one the main task of IBI. The Company has a strong expertise in development and scaling-up for GMP production of formulations also based on innovative delivery systems (nano and microparticles) and lyophilisation processes. IBI has developed a deep knowledge in liver diseases collaborating with gastroenterologist experts. Recently collaborated with innovative research centers to enable them to bring faster to market cGMP advanced therapies with recombinant proteins, nanoformulated miRNA as well as monoclonal antibodies.
IBI has been engaged for about 30 years in the study of mechanisms of action of Silibinin in several diseases, including Cushing's disease, which thanks to the preliminary work of the Max Planck Institute, the Company is aiming to start pre-clinical and clinical development. www.ibi-lorenzini.it
Max Planck Institute of Psychiatry
The Max Planck Institute of Psychiatry, which focuses primarily on research into depression and anxiety disorders, is one of the world's leading institutes in this field. Here, basic research is closely interlinked with clinical research: the Institute incorporates a 120-bed hospital, numerous specialist outpatient departments and three day units. Within these facilities, the modern research branches of genetics and proteomics are combined with the clinical analysis techniques of imaging and the measurement of brain function. The aim is to identify biomarkers of psychiatric and neurological disorders in a bid to better understand the molecular basis of these diseases. The knowledge obtained goes into the development of new therapies and drugs for the personalized medicine of tomorrow. www.psych.mpg.de
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