Researchers at Harvard University (USA) have used stem cells to identify new drugs for schizophrenia. The key, as they explain in an article published in “Stem Cell Reports”, is to use the response of the immune system itself to monitor possible therapeutic targets.
It is known that inflammation and overactivation of the immune system in the brain can cause the loss of synapses and the death of neurons, leading to neurodegenerative and psychiatric diseases.
In schizophrenia, elevated levels of the immune protein C4 have been measured in the brains of patients, and increased levels of C4 due to copy number variations are associated with increased risk of developing schizophrenia.
And, while therapies that lower C4 levels in the brain and reduce inflammation may benefit people with schizophrenia, they are currently not available.
Brain cells called astrocytes regulate the immune response and the inflammatory environment in the brain by secreting immune proteins such as C4. Consequently, astrocytes are a prime target for C4-lowering therapies.
To identify effective drugs, the research team Frances Rapino has developed an efficient method for producing large numbers of C4-secreting human astrocytes from stem cells.
In their work, the researchers followed up with a screen of 464 drugs and identified a small group of about 20 that reduced C4 secretion from astrocytes.
These drugs were effective both in healthy astrocytes and in astrocytes made from stem cells from patients with schizophrenia..
The research opens new avenues to study inflammatory responses and their regulation in human astrocytes and serves as a platform to identify therapeutic drugs in large-scale screening approaches.
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