Clinical study will evaluate the safety and feasibility of non-ablative, low-dose stereotactic radiotherapy targeting mood-regulating brain circuits

ZAP Surgical Systems, Inc., a global leader in non-invasive robotic brain surgery, today announced a landmark clinical research collaboration to evaluate precision radiomodulation therapy for treatment-resistant depression (TRD) using the ZAP-X® Gyroscopic Radiosurgery® platform^*.

The study titled the Precision Radiomodulation Therapy Project for Depression is jointly led by Beijing Anding Hospital of Capital Medical University, Chinese PLA General Hospital 301, ZAP Surgical, and Beijing NueRay Medical Technology Co., Ltd. The program was formally launched in Beijing on December 12, 2025, and represents a novel, carefully designed effort to explore non-ablative, non-invasive neuromodulation for severe psychiatric disease.

Study Overview

Building on encouraging results from recent animal studies, this interventional, non-randomized, single-blind clinical trial is designed to evaluate the safety and preliminary efficacy of low-dose stereotactic radiotherapy targeting the subgenual anterior cingulate cortex (sgACC). The sgACC has been extensively studied as a key node in mood regulation and is a validated target in invasive neuromodulation approaches for depression.

Approximately nine participants with treatment-resistant depression will be enrolled across three dose cohorts (15 Gy, 20 Gy, and 25 Gy), delivered using the ZAP-X system in a single treatment session. The primary endpoint is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) at four weeks post-treatment. Secondary endpoints include additional validated psychiatric scales, neuroimaging, and cognitive assessments through 12 weeks.

The study has received IRB approval and will be conducted in accordance with international standards for human clinical research under ClinicalTrials.gov identifier NCT07274917, with enrollment expected to begin in early 2026.

Low-Dose Circuit Modulation: A Non-Ablative Approach

Unlike traditional stereotactic radiosurgery, which relies on high-dose radiation to intentionally ablate tissue, this study investigates low-dose, non-ablative radiomodulation. The goal is to induce localized biological and metabolic changes within dysfunctional neural circuits – without neuronal destruction or tissue necrosis.

Leveraging the sub-millimeter accuracy and highly conformal dose delivery of the ZAP-X system, radiation is precisely shaped to the sgACC while minimizing exposure to surrounding healthy brain tissue. The approach is fully non-invasive, does not require anesthesia or implanted hardware, and is designed for outpatient delivery.

This strategy may offer a lower-risk alternative to invasive neuromodulation techniques such as deep brain stimulation (DBS) or vagus nerve stimulation (VNS), which require surgery, patient discomfort, permanent implants, and long-term device management.

Clinical Leadership

The study is jointly led by two internationally recognized experts:

• Gang Wang, MD, President and Professor of Psychiatry at Beijing Anding Hospital, a leading authority in mood disorders and clinical psychiatry.
• Longsheng Pan, MD, Chief Physician and Professor of Neurosurgery at the Chinese PLA General Hospital 301, specializing in stereotactic radiosurgery and functional neurosurgery.

“Treatment-resistant depression remains one of the most challenging conditions in psychiatry, with many patients failing to benefit from existing therapies,” said Gang Wang, MD, President and Professor of Psychiatry at Beijing Anding Hospital and the study’s Principal Investigator. “This study represents a cautious but important step toward exploring whether ultra-precise, low-dose radiomodulation of the subgenual anterior cingulate cortex can safely influence dysfunctional mood circuits without tissue destruction. Our goal is to generate rigorous clinical evidence that may ultimately expand non-invasive, lower-risk treatment options for patients with severe, refractory depression.”

Advancing Non-Invasive Brain Therapy

"This study reflects a careful, scientifically grounded exploration of how ultra-precise, non-invasive radiosurgery may be used to modulate dysfunctional brain circuits," said John R. Adler, MD, Founder and CEO of ZAP Surgical. "ZAP-X was purpose-built for precision, and this research represents an important step toward responsibly expanding its potential beyond traditional oncologic applications."

^* Radio-neuromodulation is not a cleared indication for stereotactic radiosurgery.

About ZAP Surgical Systems, Inc.

ZAP Surgical Systems, Inc., a global leader in non-invasive robotic brain surgery, is committed to reducing the costs and complexities that limit access to world-class radiosurgery (SRS) for the brain, head, and neck. The company manufactures the ZAP-X® Gyroscopic Radiosurgery® platform and is also pioneering new applications of high-precision SRS in areas such as depression, addiction, and obesity. Founded in 2014 by Dr. John R. Adler, Emeritus Dorothy & TK Chan Professor of Neurosurgery and Radiation Oncology at Stanford University, ZAP introduced the world’s first vault-free radiosurgery platform - eliminating the need for costly shielded treatment rooms and enabling flexible, high-visibility siting. ZAP-X also advances beyond legacy Cobalt-60 technology with a modern linear accelerator for safer, more sustainable care. Learn more at ZAP Surgical and follow us on LinkedIn.

Forward Looking Statements

This press release contains forward-looking statements, including statements regarding the potential safety, efficacy, and future clinical development of precision radiomodulation therapy. These statements are subject to risks and uncertainties that could cause actual results to differ materially. ZAP Surgical undertakes no obligation to update any forward-looking statements.

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