SBIR Phase I: A Novel Platform to Enable Directed Delivery of Therapeutics into Brain Injuries

这一小型企业创新研究(SBIR)第一阶段项目的更广泛影响/商业潜力是使创伤性脑损伤(TBI)的治疗取得变革性进展，并通过减少残疾程度和提高独立性，积极影响受伤受害者的生活，如士兵、他们的家人和一般社会。全世界每年有超过1000万人遭受脑外伤，它是人口中最活跃的部分的主要死亡和残疾原因。TBI造成的巨大财政和人员负担为开发新的创新机构和方法管理TBI提供了令人信服的理由。尽管有明显的需求，但目前还没有临床证明的有效药物来限制脑外伤的继发性损伤或加强修复。精确引导的药物输送，特别是对脑外伤损伤区域的治疗，可能会导致脑外伤临床治疗的范式转变。这种方法的临床应用潜力很大，因为靶向递送技术可以用于递送任何治疗或诊断试剂。这种靶向技术以前没有用于脑损伤的治疗，因此存在着巨大的商业机会。拟议的项目重点是开发一个靶向平台，用于对脑损伤进行特定部位的药物输送。许多神经保护剂在临床试验中失败的原因之一是这些药物的剂量限制作用。纳入有针对性的交付战略可以绕过这一点。我们已经确定了一种新的靶向多肽，可以特异性地识别脑损伤。我们建议使用动物模型来证明，将治疗药物与这种多肽相结合可以改善药物对脑损伤的输送。在这项提案中，我们将测试两种不同类型的药物(蛋白质治疗性核酸和反义核酸)与我们的靶向多肽一起，以证明治疗靶向原理的有效性。我们预计，与非靶向药物相比，静脉注射靶向药物将导致更高的脑损伤累积。这一策略有望改善脑损伤的治疗和诊断。它还可能促进对与脑损伤相关的分子变化的理解，并可能提供新的治疗靶点。有了这一平台技术，脑损伤治疗的变革性进展有望随之而来，其形式包括提高疗效、减少副作用和易于管理

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to enable transformative advances into the treatment of traumatic brain injury (TBI) and positively impact the lives of injury victims, such as soldiers, their families and the society in general by reducing the degree of disability and increasing independence. With over 10 million people worldwide sustaining TBI annually, it is the leading cause of death and disability in the most active segment of the population. The enormous financial and human suffering burden of TBI provides a compelling rationale for the development of novel and innovative agents and approaches to TBI management. Despite an obvious need, there are currently no clinically proven, effective drugs to limit secondary injury or enhance repair in TBI. Precision-guided delivery of drugs specifically to injured areas in the TBI brain may result in a paradigm shift in the clinical management of TBI. The potential for clinical application of such an approach is high, as the targeted delivery technology can be used for delivering any therapeutic or diagnostic agent. Such a targeting technology has not previously been available for treatment of brain injury and therefore there exists a huge commercial opportunity. The proposed project focuses on developing a targeting platform for site-specific delivery of drugs to brain injury. One of the reasons for the failure of many neuro-protective agents in clinical trials is due to the dose limiting effects of these drugs. Incorporating a targeted delivery strategy can circumvent this. We have identified a novel targeting peptide that specifically recognizes TBI. Using animal models, we propose to demonstrate that combining therapeutics with this peptide can improve delivery of drugs to brain injury. In this proposal, we will test two different types of drugs (a protein therapeutic and antisense nucleic acids) in conjunction with our targeting peptide to demonstrate the validity of the principle of therapeutic targeting. We expect that an intravenous administration of targeted drugs will lead to a higher accumulation in brain injury than untargeted drug. This strategy can be expected to improve therapy, and also diagnosis, of brain injuries. It may also advance the understanding of the molecular changes associated with brain injuries and may provide new therapeutic targets. With this platform technology, transformative advances in brain injury treatment in the form of increased efficacy, reduced side effects, and ease of administration are expected to ensue