STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection

这个小企业技术转移(STTR)第一阶段项目的更广泛的影响/商业潜力是一种新型医疗设备疗法，用于改善接受器官移植的患者的临床结果。全球每年进行的肾脏移植手术超过10万例，高达20%的患者发生了排斥反应。现有的药物治疗，包括免疫抑制剂，往往会产生严重的副作用，每位患者每年的财务成本高达近30,000美元。该项目旨在开发一种外部系统，以减少炎症反应，从而减少与移植相关的不良事件，并延长新器官的寿命。除了肾脏器官移植，该技术还为其他器官移植以及各种慢性炎症性疾病提供了潜在的可扩展性。这个小型企业技术转移(STTR)第一阶段项目旨在开发一种新型的基于超声波的医疗设备疗法，以减少器官移植后的排斥反应。外部系统刺激脾中的靶向神经，通过既定的生理途径调节免疫系统。该提案旨在优化移植模型中的各种超声参数，以进一步开发出功能原型。主要目标包括1)开发一种临床前换能器，向目标脾神经提供所需的治疗性超声波波形；2)使用公认的临床前同种异体皮肤移植模型优化治疗参数；3)在公认的临床前模型中验证促炎细胞因子的原位减少。这项建议的结果将证明这一技术方法在最终临床患者翻译方面的安全性和可行性。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is a novel medical device therapy for improving the clinical outcomes of patients receiving organ transplants. Over 100,000 kidney transplant procedures are performed worldwide each year, with up to 20% of patients experiencing rejection. Existing drug treatments, including immunosuppressants, often entail significant side effects with a high financial cost of nearly $30,000 per year per patient. This project aims to develop an external system for reducing inflammatory responses thereby reducing adverse events associated with the transplant and extending the lifetime of the new organ. Beyond kidney organ transplantation, the technology provides potential extensibility for other organ transplants as well as addressing various chronic inflammatory diseases. This Small Business Technology Transfer (STTR) Phase I project aims to develop a novel ultrasound-based medical device therapy for reducing post-transplant organ rejection. The external system stimulates targeted nerves in the spleen to modulate the immune system through established physiologic pathways. The proposal aims to optimize various ultrasonic parameters in a transplant model to further development towards a functional prototype. The key objectives include 1) developing a pre-clinical transducer delivering the desired therapeutic ultrasonic waveform to the targeted splenic nerves, 2) optimizing the treatment parameters using an accepted preclinical skin allograft model, and 3) validating the reduction in pro-inflammatory cytokines in situ in accepted preclinical models. The results of this proposal will demonstrate the safety and feasibility of this technological approach toward eventual clinical patient translation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.