Cushing Disease is caused by a tumour in the pituitary gland in the brain.
The tumour secrets increased amounts of the stress hormone adrenocorticotropin (ACTH) followed by cortisol release from the adrenal glands leading to rapid weight gain, elevated blood pressure and muscular weakness.
Scientists around Gunter Stalla, endocrinologist at the Max Planck Institute of Psychiatry in Munich, have discovered in cell cultures, animal models and human tumour tissue that a harmless plant extract can be applied to treat Cushing Disease.
"Silibinin is the major active constituent of milk thistle seeds. It has an outstanding safety profile in humans and is already used for the treatment of liver disease and poisoning," said Marcelo Paez-Pereda, leading scientist of the study.
After silibinin treatment, tumour cells resumed normal ACTH production, tumour growth slowed down and symptoms of Cushing Disease disappeared in mice.
In 2013, the Max Planck scientists filed a patent on a broad family of chemical and natural compounds, including silibinin, to treat pituitary tumours.
Compared to humans, of which only 5.5 in 100,000 people worldwide develop Cushing Disease, this condition is very common in several pets.
"We knew that Cushing Disease is caused by the release of too much ACTH. So we asked ourselves what causes this over production and how to stop it," said Paez-Pereda.
In their experiments the researchers found tremendously high amounts of the heat shock protein 90 (HSP90) in tumour tissue from patients with Cushing Disease.
In normal amounts HSP90 helps to correctly fold another protein, the glucocorticoid receptor which in turn inhibits the production of ACTH.
"As there are too many HSP90 molecules in the tumour tissue, they stick to the glucocorticoid receptor," said Paez-Pereda.
"We found that silibinin binds to HSP90 thus allowing glucocorticoid receptor molecules to dissolve from HSP90. With silibinin we might have discovered a non-invasive treatment strategy not only for the rare Cushing Disease but also for other conditions with the involvement of glucocorticoid receptors such as lung tumours, acute lymphoblastic leukemia or multiple myeloma," Paez-Pereda added.
The study was published in the journal Nature Medicine.
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