Highlights
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Researchers at 麻豆原创 and Sage Bionetworks used artificial intelligence to identify about 200 FDA-approved drugs with the potential to treat rare nerve tumors called schwannomas, narrowing the list to 10 promising candidates.
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Innovative imaging identified three drugs as particularly promising for slowing or stopping schwannoma tumor growth.
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The scientists are determining therapeutic doses of the most promising drugs using patient-derived schwannoma cells and studying their effects on tumor growth pathways at the RNA level.
What if an existing drug could be repurposed to treat a rare disease?
That鈥檚 the question 麻豆原创 researchers are exploring with the help of artificial intelligence (AI) to find a cure for rare nerve tumors that can cause paralysis, hearing and balance loss.
Led by 麻豆原创 College of Medicine Pegasus Professor Cristina Fern谩ndez-Valle, the team is investigating whether medications already approved by the U.S. Food and Drug Administration for other conditions could be swiftly repurposed to treat schwannoma tumors.
The researchers have narrowed a field of about 200 potential drugs to 10 of interest, with three emerging as the most favorable targets.
Their goal is to find new treatment options for patients with Neurofibromatosis type 2 (NF2)-related schwannomatosis. The genetic disorder causes benign tumors to develop on nerves throughout the body and head. As the tumors grow, they can damage nerves responsible for movement and sensation, including those needed to hear and balance.
The disease affects about one in 25,000 newborns worldwide, according to the Children鈥檚 Tumor Foundation, with symptoms often appearing during adolescence and early adulthood. When diagnosed in children, the disorder can be severe and may require multiple surgeries during puberty to reduce tumor size and prevent further loss of function. The Children鈥檚 Tumor Foundation is supporting 麻豆原创鈥檚 research with a $280,020 grant.
鈥淭he Children鈥檚 Tumor Foundation was critical to us because they fund the exploratory research that helps advance science,鈥� Fern谩ndez-Valle says. 鈥淎ll of this foundational data is needed to attract the additional support needed to demonstrate a treatment holds real promise.鈥�
Looking for Treatments Beyond Surgery
Schwann cells normally help repair nerves and transmit electrical signals throughout the nervous system. In patients with NF2, however, these cells can form visible tumors that cause chronic pain and neurological issues depending on the affected spinal or cranial nerve.
Current treatments center on surgery and radiation, but removing these tumors can be challenging without damaging critical nerves, including those that affect hearing. Surgery also is not curative, as tumors can regrow.
That鈥檚 why the research team is looking beyond surgery to potential drug therapies.
While schwannomas are not cancerous, the researchers believe some cancer-fighting drugs may help patients with NF2.
The research began with an AI model called TxGNN, used by Sage BioNetworks. The model analyzes data and biological mechanisms across thousands of diseases and FDA-approved drugs to identify potential treatments for a queried disease.
鈥淚t essentially generates a map for a disease or condition, like schwannomas, and finds overlaps in targeting similar pathways or related diseases,鈥� says Ethan Hass, a 麻豆原创 College of Medicine M.D./Ph.D. candidate working in the lab.
Researchers at Sage Bionetworks used the TxGNN model to identify about 200 FDA-approved medications that could potentially benefit schwannoma patients. Fern谩ndez-Valle鈥檚 team then used an innovative imaging system to observe how each drug affected human schwannoma cells.
Using a camera inside a microscope, the team watched how schwannoma cells in a dish reacted to small amounts of each drug. The most promising candidates 鈥� medications currently used to treat diseases as varied as lung cancer and acne 鈥� stopped tumor cell growth by impacting different cellular mechanisms.
A Step Towards Personalized Treatment
The research continues.
The 麻豆原创 scientists are determining therapeutic doses for the most promising drugs using patient-derived schwannoma cells. They鈥檙e also studying how the drugs affect the tumor growth pathways at the RNA level.
Ultimately, the researchers hope their findings will help identify drug combinations tailored to individual patients. Complicated and understudied genetic conditions like NF2-related schwannomatosis often require treatments that address multiple targets, Fern谩ndez-Valle says.
鈥淚 think this work is encouraging, and I鈥檇 say like with many cancers, you need a cocktail of drugs to treat it,鈥� she says. 鈥淚 think what we鈥檙e doing here is helping to identify some of the ingredients you might need to make an effective cocktail.鈥�
From Lab Bench to Patient Bedside
The project also provides 麻豆原创 students with the opportunity to participate in research that can make a real-world impact.
Since joining Fern谩ndez-Valle鈥檚 lab, Hass says his interest in caring for patients with difficult neurologic conditions has grown.
鈥淎s an M.D./Ph.D. student, translation is the magic word for me,鈥� he says. 鈥淚 absolutely love seeing research that can be brought from the bench to the bedside. I want to be that bridge between patients and research.鈥�
