Novartis is re-sharing these Cushing’s disease resources for Rare Disease Day:
Filed under: adrenal, Cushing, Cushing's, pituitary, Rare Diseases, Video | Tagged: Cushing's Disease, Dr. Harvey Cushing, infographic, Rare Disease Day, video | 2 Comments »
The USP8 mutations identified in adenomas of the pituitary gland lead to overproduction of ACTH. Panel A: ACTH-producing cells in a normal gland. The other panels show cells non-mutant (B) or mutant (C) for USP8. Credit: S. Sbiera, Universität Würzburg
Benign tumors in the pituitary gland lead to uncontrolled secretion of the stress hormone cortisol by the cells of the adrenal cortex. An international research effort has now characterized a new mechanism that triggers the syndrome.
Many individuals who suffer from Cushing syndrome are easy to recognize: They tend to be overweight particularly around the waist, and have round faces and bull necks. In addition to these obvious features, most of them have high blood pressure, develop muscle weakness, become diabetic and are extremely susceptible to infection. Cushing syndrome can often be treated effectively by surgical intervention, but patients succumb to infections or cardiovascular disease if the condition is left untreated.
In their efforts to understand how benign tumors in the pituitary provoke the development of Cushing’s disease, researchers based in Munich, Würzburg and Tokyo led by Professor Martin Reincke (Director of LMU’s Medical Clinic IV at Munich University Medical Center) have now pinpointed a novel molecular mechanism responsible for the condition. The results of the study have just appeared in Nature Genetics.
The perils of incessant secretion
All of the symptoms that typify Cushing syndrome are attributable to the unregulated secretion of the hormone cortisol – generally referred to as cortisone. Cortisol is normally released into the bloodstream only in stress situations, and helps the organism to cope with the challenge. However, when secreted in an uncontrolled fashion, the result is physiological havoc. Cortisol is synthesized in, and secreted by specialized cells in the adrenal cortex in response to the binding of a different hormone, the adrenocorticotropic hormone (ACTH). ACTH in turn is produced in the pituitary gland. Excessive cell proliferation in the pituitary can result in the formation of benign tumors (adenomas), which may lead to overproduction of ACTH and a corresponding increase in the level of circulating cortisol. However, the connecting links between the two processes are incompletely understood.
“We have now shown that tumor cells in more than one-third of patients with Cushing’s disease carry a mutation in one specific gene, which codes for an enzyme called ubiquitin-specific protease 8,” says Martin Fassnacht (Würzburg University Hospital), one of the authors of the publication. The mutation was discovered in the course of a detailed genetic characterization of benign tumors of the pituitary gland that overproduced ACTH.
Protease defect sets off a chain reaction
Ubiquitin-specific protease 8 (USP8) is one of a family of enzymes which play a key role in the destruction of proteins that are required only transiently by cells. One such protein is the receptor for epidermal growth factor (EGF), which is degraded and disposed of only when the USP8 gene is inactive, and no USP8 protein is present. The collaboration found that the effect of the mutations identified in pituitary tumor tissues is to keep the USP8 permanently active. As a consequence, the EGF receptor escapes demolition, and is instead recycled to its site of action on the cell membrane. The upshot of this is a life-threatening chain reaction, in which unrestrained synthesis of ACTH leads to uninhibited secretion of cortisol. “The identification of mutations in USP8 is a significant finding, because it opens up entirely new diagnostic and therapeutic approaches to the management of Cushing’s disease,” Martin Reincke adds.
Long-term focus on Cushing’s disease
Indeed, this is not the first time that the collaboration between the teams in Munich and Würzburg has shed light on the pathogenesis of Cushing’s disease. The two groups have previously identified mutations in a gene that is expressed in the adrenal cortex as a frequent cause of the pathological secretion of cortisol in a different patient population. The results of that study appeared in February 2014 in the “New England Journal of Medicine“. And only last week, a paper providing a detailed characterization of the molecular effects of the latter set of mutations was published in “Nature Communications“.
Explore further: Cushing’s syndrome: A genetic basis for cortisol excess
More information: “Mutations in the deubiquitinase gene USP8 cause Cushing’s disease.” Nature Genetics (2014) DOI: 10.1038/ng.3166
Filed under: Cushing's, pituitary | Tagged: ACTH, Adrenal cortex, buffalo hump, Cushing's Disease, diabetics, high blood pressure, infections, moonface, Mutation, stress, ubiquitin-specific protease 8, USP8, weight | Leave a comment »
Global Markets Direct’s, ‘Pituitary ACTH Hypersecretion (Cushing’s Disease) – Pipeline Review, H2 2014’, provides an overview of the Pituitary ACTH Hypersecretion (Cushing’s Disease)’s therapeutic pipeline.
This report provides comprehensive information on the therapeutic development for Pituitary ACTH Hypersecretion (Cushing’s Disease), complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action (MoA), route of administration (RoA) and molecule type, along with latest updates, and featured news and press releases. It also reviews key players involved in the therapeutic development for Pituitary ACTH Hypersecretion (Cushing’s Disease) and special features on late-stage and discontinued projects.
Global Markets Direct’s report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data and information sourced from Global Markets Direct’s proprietary databases, Company/University websites, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources, put together by Global Markets Direct’s team. Drug profiles/records featured in the report undergoes periodic updation following a stringent set of processes that ensures that all the profiles are updated with the latest set of information. Additionally, processes including live news & deals tracking, browser based alert-box and clinical trials registries tracking ensure that the most recent developments are captured on a real time basis.
The report enhances decision making capabilities and help to create effective counter strategies to gain competitive advantage. It strengthens R&D pipelines by identifying new targets and MOAs to produce first-in-class and best-in-class products.
Note*: Certain sections in the report may be removed or altered based on the availability and relevance of data for the indicated disease.
Scope
– The report provides a snapshot of the global therapeutic landscape of Pituitary ACTH Hypersecretion (Cushing’s Disease)
– The report reviews key pipeline products under drug profile section which includes, product description, MoA and R&D brief, licensing and collaboration details & other developmental activities
– The report reviews key players involved in the therapeutics development for Pituitary ACTH Hypersecretion (Cushing’s Disease) and enlists all their major and minor projects
– The report summarizes all the dormant and discontinued pipeline projects
– A review of the Pituitary ACTH Hypersecretion (Cushing’s Disease) products under development by companies and universities/research institutes based on information derived from company and industry-specific sources
– Pipeline products coverage based on various stages of development ranging from pre-registration till discovery and undisclosed stages
– A detailed assessment of monotherapy and combination therapy pipeline projects
– Coverage of the Pituitary ACTH Hypersecretion (Cushing’s Disease) pipeline on the basis of target, MoA, route of administration and molecule type
– Latest news and deals relating related to pipeline products
Reasons to buy
– Provides strategically significant competitor information, analysis, and insights to formulate effective R&D development strategies
– Identify emerging players with potentially strong product portfolio and create effective counter-strategies to gain competitive advantage
– Develop strategic initiatives by understanding the focus areas of leading companies
– Identify and understand important and diverse types of therapeutics under development for Pituitary ACTH Hypersecretion (Cushing’s Disease)
– Plan mergers and acquisitions effectively by identifying key players of the most promising pipeline
– Devise corrective measures for pipeline projects by understanding Pituitary ACTH Hypersecretion (Cushing’s Disease) pipeline depth and focus of Indication therapeutics
– Develop and design in-licensing and out-licensing strategies by identifying prospective partners with the most attractive projects to enhance and expand business potential and scope
– Modify the therapeutic portfolio by identifying discontinued projects and understanding the factors that drove them from pipeline
Read the full report: http://www.reportlinker.com/p02458443-summary/view-report.html
Filed under: Cushing's, pituitary, Rare Diseases | Tagged: ACTH, ACTH Hypersecretion, Cushing's Disease, pituitary | Leave a comment »
It’s NOT as rare as they thought…
Epidemiologists forecast an increase in the diagnosed prevalent cases of CS in the 6MM, from 32,634 diagnosed prevalent cases in 2013 to 34,573 diagnosed prevalent cases in 2023, with an annual growth rate of 0.59% in the forecast period. In 2023, the US will have the highest number of diagnosed prevalent cases of CS, with 17,162 diagnosed prevalent cases.
For this analysis, The publisher epidemiologists used data available from Orphanet to construct the 10-year epidemiological forecast for the diagnosed prevalent cases of CS, Cushing’s disease, ectopic ACTH CS, adrenal adenoma CS, and adrenal carcinoma CS in the 6MM. The forecast provides the age- and sex-specific diagnosed prevalent cases of CS subtypes in the six markets, providing a comprehensive view of CS. In addition, this analysis provided detailed, clinically relevant segmentations for Cushing’s disease in order to improve the management of the disease.
Scope
Read the article here: http://www.businesswire.com/news/home/20141103006612/en/Research-Markets-EpiCast-Report-Cushings-Syndrome–#.VFgvl5PF9HA
Filed under: adrenal, Cancer, Cushing's, pituitary, Rare Diseases | Tagged: ACTH, adrenal adenoma, adrenal carcinoma, Cushing's Disease, Cushing's Syndrome, ectopic, Epidemiologists, pituitary | Leave a comment »
CushieBlog 