Stories Caught our Eye: Advances in Brain Radiotherapy, and a New Drug Discovery in Schizophrenia

Avoiding the hippocampus during whole-brain radiotherapy prevents cognitive side effects (Adonica Shaw)

Whole-brain radiotherapy can be delivered more safely to patients with brain metastases by avoiding the hippocampus according to a new phase III trial.

At the beginning of the study, scientists hypothesized that radiation to the hippocampal stem cells played a role in cognitive decline. 500 patients were randomized to whole brain radiotherapy, some with and without hippocampal avoidance. The results of the clinical trial found a 26% relative reduction in risk of cognitive toxicity following whole brain radiation therapy with hippocampal avoidance versus whole brain radiotherapy. The cognitive function benefit of hippocampal avoidance did not differ by age.

“This study demonstrates that we can deliver whole brain radiotherapy with similar cognitive outcomes as radiosurgery,” said lead author and co-principal investigator of the phase III trial Vinai Gondi, MD, director of research at the Northwestern Medicine Chicago Proton Center and co-director of the Brain Tumor Center at Northwestern Medicine Cancer Center Warrenville. “These trial results revolutionize our understanding of the cognitive effects of brain irradiation in a manner that has far-reaching implications in terms of the safer radiotherapy treatment of primary or metastatic brain tumors.”

Brain metastases, cancer cells that have spread to the brain from primary tumors in other organs, is one of the most common cancer conditions managed by radiation oncologists. Due to concerns about cognitive decline, whole brain radiotherapy is currently often the last resort, even though it is one of the most effective treatments for brain metastases.

By establishing that the hippocampal region is sensitive to radiation, treatment plans for brain metastases or other brain tumors can employ advanced techniques such as intensity-modulated radiation therapy (IMRT) or proton therapy to reduce dose to the hippocampus and offer brain therapy with less toxicity.

Better model to help speed up new drugs for schizophrenia (Kevin McCormack)

One of the problems in developing new treatments for diseases is finding a model that accurately reflects how a new treatment might work in people. Typically, we’ll test some new approach on a mouse model of a disease, to see if it is safe and works. But often what works in a mouse doesn’t work in people. Now a new study in the journal Nature Communications may have found a better model to test drugs for people with schizophrenia.

Right now, all antipsychotic drugs approved by the Food and Drug Administration (FDA) for schizophrenia target one specific dopamine receptor in the brain. Dopamine is a chemical that acts as a messenger in the brain and it’s thought that imbalances in this receptor are a leading cause of schizophrenia. However, around two-thirds of people with the condition don’t respond to the medications that target this receptor.

So, researchers at the Icahn School of Medicine at Mount Sinai, Eli Lilly and Company, and Sema4 thought that maybe a better way to test potential new medications would be on cells that came from people who actually have schizophrenia, rather than a mouse.

They took cells from 12 people with schizophrenia and 12 healthy people, and turned those cells into neural progenitor cells, the kind of brain cell affected by the disease. They then tested those cells against 135 different medications and found that the patient-derived cells provided lots more information about how those cells would affect someone with schizophrenia than traditional testing methods.

In a news release Adam Margolin, from the Icahn Institute, said these findings could have wider implications:

“This study nicely illustrates the importance of using an integrative genomics approach for improving drug discovery and, ultimately, patient care. The results should be immediately applicable not only to drug discovery for schizophrenia but also more broadly to a wide range of diseases for which more biologically relevant screening models are long overdue.

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