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

该小企业创新研究 (SBIR) 第一阶段项目的更广泛影响/商业潜力是推动创伤性脑损伤 (TBI) 治疗的变革性进展，并通过降低残疾程度和增强独立性，对士兵、其家人和整个社会等受伤受害者的生活产生积极影响。全球每年有超过 1000 万人遭受 TBI，它是最活跃人群死亡和残疾的主要原因。 TBI 带来的巨大的经济和人类痛苦负担为开发新型创新药物和 TBI 管理方法提供了令人信服的理由。尽管有明显的需求，但目前还没有经过临床证明的有效药物来限制继发性损伤或增强 TBI 的修复。精确引导药物输送到 TBI 大脑损伤区域可能会导致 TBI 临床管理的范式转变。这种方法的临床应用潜力很高，因为靶向递送技术可用于递送任何治疗或诊断剂。这种靶向技术此前尚未可用于治疗脑损伤，因此存在巨大的商业机会。拟议项目的重点是开发一个靶向平台，用于针对脑损伤进行定点递送药物。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。结合有针对性的交付策略可以避免这种情况。我们已经鉴定出一种特异性识别 TBI 的新型靶向肽。我们建议使用动物模型来证明，将疗法与这种肽相结合可以改善药物对脑损伤的递送。在本提案中，我们将测试两种不同类型的药物（蛋白质治疗剂和反义核酸）与我们的靶向肽结合，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，静脉注射靶向药物会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。借助该平台技术，预计脑损伤治疗将取得革命性进展，提高疗效、减少副作用和易于给药

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