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Generation of human steroid-producing organoids: a new approach to treat adrenal insufficiency

Periodic Reporting for period 2 - GHSO (Generation of human steroid-producing organoids: a new approach to treat adrenal insufficiency)

Reporting period: 2021-06-01 to 2022-05-31

Adrenal insufficiency is a disorder that occurs when the adrenal glands do not produce enough levels of certain hormones, including cortisol, a hormone essential for life. Current treatments for adrenal insufficiency are based on hormone replacement therapy (HRT), consisting of 2 or 3 daily doses of the missing hormones in a pill format.
The general purpose of this proposal is to find alternative treatments for patients suffering from adrenal insufficiency using cells that can produce hormones, generated in the laboratory.
The overall significance and importance of this technology is the ability to transplant hormone-producing cells that can be properly regulated by the patient’s body, responding with adequate hormone secretion in a time and dose dependent manner. To avoid rejection of the implanted cells by the immune system, we aim to encapsulate (protect) cells into devices developed for this purpose.
The main milestones achieve during the Marie-Curie fellowship were: 1) We have been able to generate billions of steroid-producing cells. 2) Steroid-producing cells can produce the human steroid cortisol, one of the main regulators of human physiology. 3) Human steroid-producing cells are able to respond to ACTH, the main stimulator of cortisol production in the adrenal gland.
If animal in vivo experiments proof the success of this technology, patients suffering from adrenal insufficiency can benefit from a significant improvement of their quality of life. Instead of taking life-long medication, which it is far from optimal, patients might use a cellular therapy-base approach, with cells that can autonomously sense the physiological requirements of the body during time.
Towards the end of the funding period, we have also filed provisional patent applications in Europe (EP 22160580.4) and US (No. 63/263795), entitled “A method for producing induced steroidogenic cells and use thereof in cell therapy”. This will allow, in the future, to use this approach in the industry contex to develop good manufacturing practice (GMP)-grade cellula products that can be used in the clinic.
The project GHSO has been presented to both lay and specialized audience, in Germany (Uniklinikum Dresden), USA (Boston Children's Hospial, Harvard Medical School) and Spain (Hospital Clínic de Barcelona). I authored a publication adapted for kids aged 7-9 and their parents for the journal “Frontiers of Young Minds” (doi: 10.3389/frym.2022.683150) published on April 24th 2022.
The generation of billions of steroid-producing cells in the lab from pluripotent stem cells can have an impact on the quality of life of patients with adrenal insufficiency. Current work, continued after the Marie-Curie fellowship, is addressing the functionality of these cells in in vivo models of adrenal insufficiency.