News

Seattle, WA – August 11, 2025

Washington Research Foundation (WRF) has awarded a $275,000 technology commercialization grant to Nino Ramirez, Ph.D., of Seattle Children’s to enable the development of a treatment that could halt the progression of schizophrenia. Ramirez and his colleagues used a grant of $100,000 from WRF in 2023 to develop a molecule that they will use to degrade the protein C4, which is naturally produced in the body and appears to be linked to schizophrenia when present in excessive levels.

Schizophrenia affects around 1 in 300 people worldwide. Antipsychotics can alleviate some of the condition’s most severe symptoms, such as hallucinations and delusions, but patients must take them regularly—often daily—for them to be effective. Because most antipsychotics do not target schizophrenia-specific mechanisms, many patients experience side effects while using these medications, including drowsiness and movement disorders. There is currently no cure for schizophrenia.

Ramirez, a professor and the director of the Norcliffe Foundation Center for Integrative Brain Research, is working with colleagues to test a different therapeutic approach. C4 is a protein that is part of the immune system and a key component of the body’s synaptic pruning pathway, which helps to regulate connections between the brain’s cells (neurons) and remove those deemed to be inefficient or unnecessary. Researchers have identified that high C4 levels appear to be correlated with excessive synaptic pruning and the progression of schizophrenia.

With help from the earlier WRF grant, Ramirez and his team developed a Bispecific Complement Engaging Protein (BiCEP) that can bind to C4, remove it from circulation and mark it for degradation by most cells of the body, including brain cells. This, he believes, could be administered to patients who show early symptoms or higher risk of developing schizophrenia, to slow or halt the progression of the condition. As C4 plays an important role in effective synaptic pruning when expressed at the right levels, dosages of a BiCEP-based therapeutic could be modified according to the patient’s individual needs.

“This is probably the most exciting grant I have ever received,” Ramirez said. “It was conceived in a team effort with Dr. Jim Olson from the Ben Towne Cancer Center. Team science is the future of pediatric research which allows us to rigorously translate bench research into a cure and therapy in patients using the fantastic infrastructure that we created here at the Seattle Children’s Research Institute. This grant is also the result of our great interaction with the Washington Research Foundation, which provided important scientific guidance at every step of the grant”.

Akinsola Oyelakin, Ph.D., a postdoctoral scholar in the Invent at Seattle Children’s program that WRF supported with a $12.5 million pledge in 2022, works in Ramirez’s lab and has been a key collaborator on the project.

This approach, he said, is very different from the way existing antipsychotics work and their goal is to preserve the physical connections that would otherwise be lost as patients transition from having psychosis to developing schizophrenia.

“We think doing this will either halt or slow down progression long enough for the brain to recover and develop compensation mechanisms against further cognitive decline,” Oyelakin said. “If this works, it will improve the outcome for individuals clinically at risk of developing schizophrenia and improve the way many other neurological disorders are treated. We realize that funding for unconventional ideas such as ours is very sparse, and we are extremely grateful for the financial support of the Washington Research Foundation.”

Meher Antia, Ph.D., WRF’s director of grant programs, said, “The Invent at Seattle Children’s program is quickly becoming an important source of creative ideas to develop novel therapeutics, as demonstrated by this successful application to WRF’s technology commercialization grant program. We are pleased that our funding will help to derisk this technology and help advance this potentially disease-modifying therapy for schizophrenia.”

Over the next 18 months, Ramirez and his colleagues will use this latest funding from WRF to conduct proof-of-principle testing in mouse models, generating important preclinical data on BiCEP’s effectiveness in reducing C4 levels. If results support Ramirez’s hypothesis, this will be a critical step toward filing for an investigational new drug (IND) ahead of possible clinical trials.

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About Washington Research Foundation:

Washington Research Foundation (WRF) supports research and scholarship in Washington state, with a focus on life sciences and enabling technologies.

WRF was founded in 1981 to assist universities and other nonprofit research institutions in Washington with the commercialization and licensing of their technologies. WRF became one of the foremost technology transfer organizations in the nation, earning more than $445 million in licensing revenue for the University of Washington. To date, WRF has provided over $182 million in grants to the state’s research institutions.

WRF Capital, the investment vehicle for Washington Research Foundation, has backed 132 local startups since 1996. Returns support the Foundation’s grantmaking and investment programs.