Description:
OBJECTIVE: The objective of this effort is to develop a new innovative technology that accelerates or directs muscle reinnervation and the establishment of neuromuscular junctions following peripheral nerve denervation. DESCRIPTION: Segmental nerve defects have limited potential for spontaneous recovery and are often associated with devastating functional deficiencies. It is known that 5-6% of all military injuries involve major injury to a peripheral nerve. Before World War II (WW II) nerve injuries were repaired as simple reapproximation and suturing procedures often conducted under tension. They were often further complicated by surrounding tissue damage and infection. Poor outcomes from these procedures were discovered to be the result of failed axonal regeneration at the site of repair. In addition to physically bridging the defect, we recognize the need for medical interventions to promote or direct muscle reinnervation primarily the reestablishment of neuromuscular junctions. The literature suggests the application of mechanical stimulation and growth factors show promise as potential therapies. The inducible expression of neurotrophic factors by mesenchymal progenitor cells within damaged muscle may speak to an endogenous pathway that could also be enhanced to promote reinnervation. As the therapeutic field continues to advance, it is likely more nanotechnology, cellular, mechanical, biologic or pharmacological components may also be incorporated into therapeutic strategies to promote or direct muscle reinnervation and create neuromuscular junctions to facilitate the repair of peripheral nerve defects and enhance functional muscle recovery. PHASE I: Conceptualize and design an innovative solution for repair and regeneration that will promote or direct the formation of neuromuscular junctions thereby facilitating the repair of peripheral nerve defects. Such constructs should be biomaterial driven and may include nanotopology, cellular, tissue or biological components meant to facilitate controlled axonal outgrowth or promote ensheathment. It is likely that the most successful constructs would incorporate two or more of the described components. The required Phase I deliverables will include: 1) a research design for engineering the scaffold and 2) A preliminary prototype with limited testing to demonstrate in vitro proof-of-concept evidence that demonstrate axonal bridging via the scaffold conduit (to be executed at Phase I). Other supportive data from in vivo proof-of-feasibility studies demonstrating muscle reinnervation which lead to functional improvement may also be provided during this 6-month Phase I period. PHASE II: The researcher shall design, develop, test, and demonstrate a prototype therapeutic that implements the Phase I methodology to promote or direct muscle reinnervation. The researcher shall describe in detail the plan for the Phase III effort. PHASE III DUAL USE APPLICATIONS: Plans on the commercialization/technology transition and regulatory pathway should be executed here and lead to FDA clearance/approval. They include: 1) identifying a relevant patient population for clinical testing to evaluate safety and efficacy and 2) GMP manufacturing sufficient materials for evaluation. The small business should also provide a strategy to secure additional funding from non-SBIR government sources and /or the private sector to support these efforts. Military application: The desired therapy will allow military practitioners to apply the therapy. Commercial application: Healthcare professionals world-wide could utilize this product as a therapy meant to improve the standard of care presently available to patients suffering from peripheral nerve denervation. REFERENCES: 1."Immediate Care of the Wounded."Clifford C. Cloonan. Copyright 2007 The Brookside Associates, Ltd. All Rights Reserved http://www.operationalmedicine.org/TextbookFiles/Cloonan/Disability.pdf 2."Acute nerve injury."Medscape Reference., Sep 23, 2011. http://emedicine.medscape.com/article/249621-overview# 3."Mechanical stimulation of paralyzed vibrissal muscles following facial nerve injury in adult rat promotes full recovery of whisking."Neurobiol Dis., April 2007; Vol. 26, No. 1; p 229-42. 4."Enhanced reinnervation of the paralyzed orbicularis oculi muscle after insulin-like growth factor-I (IGF-I) delivery to a nerve graft."J Reconstr Microsurg., July 2001; Vol. 17, No. 5; p 357-62. 5."Inducible Expression of Neurotrophic Factors by Mesenchymal Progenitor Cells Derived from Traumatically Injured Human Muscle."Mol Biotechnol., Sep 9, 2011. Ahead of press. http://www.springerlink.com/content/v086x68275386vj0/fulltext.pdf
