What causes Insufficiency Degenerative Disc Disease? DDD - - PowerPoint PPT Presentation
The NEXT Treatment for Low Back Pain Tom Hedman, Ph.D. Associate Research Professor Center for Biomedical Engineering and Department of Neurosurgery University of Kentucky Founder, General Partner and Chief Scientific Officer
Associate Research Professor Center for Biomedical Engineering and Department of Neurosurgery University of Kentucky Founder, General Partner and Chief Scientific Officer – Orthopeutics, LP Founder, Chairman – Intralink Spine, Inc. Founder, Board Member – Equinext, LLC September 2013
Mechanical Insufficiency Nutritional Deficiency Loss of GAGs/ Hydration
Genetics
Fissuring/EP Damage Proinflammatory Cytokine Release Neo-Innervation Edema Joint Instability/ Afferent Nerve Strain Disc Bulge/ Neural Compression
adjacent to EP
Underlying Factors Pain Generators Other Criteria
augmentation
crosslinking of native ECM
biomimetic approach
covalent bonds
NEXTTM NEXT - Nonsurgical EXogenous Crosslink Therapy genipin
Underlying Factors Pain Generators Other Criteria
Follow-On Work By Others
Yerramalli CS, Chou AI, Miller GJ, Nicoll SB, Chin KR, Elliott DM, The effect of nucleus pulposus crosslinking and glycosaminoglycan degradation on disc mechanical function. Biomech.Model.Mechanobiol, 2007;6:13-20. Barbir A, Michalek AJ, Abbott RD, Iatridis JC., Effects of enzymatic digestion on compressive properties of rat intervertebral discs, J
Chuang SY, Lin LC, Tsai YC, Wang JL., Exogenous crosslinking recovers the functional integrity of intervertebral disc secondary to a stab injury., J Biomed Mater Res A. 2010 Jan;92(1):297-302. Fessel G, Wernli J, Li Y, Gerber C, Snedeker JG., Exogenous collagen cross-linking recovers tendon functional integrity in an experimental model of partial tear, J Orthop Res. 2011 Nov 18. doi: 10.1002/jor.22014. [Epub ahead of print] Fessel G, Gerber C, Snedeker JG., Potential of collagen cross-linking therapies to mediate tendon mechanical properties, J Shoulder Elbow
Some of Our 28 Peer-Reviewed Publications
Hedman, T, Saito, H., Vo, C. and Chuang, S-Y, Exogenous Crosslinking Increases the Stability of Spinal Motion Segments, Spine 31(15):E480- 485, 2006. Chuang, S-Y, Odono, R.M., Hedman, T.P., Effects of Exogenous Crosslinking on In Vitro Tensile and Compressive Moduli of Lumbar Intervertebral Discs , Clinical Biomechanics, 22(1):14-20, 2007. Chuang, S-Y, Popovich, JM, Lin, L-C, Wang, S-J, Hedman, T, The Effects
Intervertebral Disc Subjected to Compressive Creep Loading and Unloading Spine, Spine, 35(24):E1362-6, 2010. Chuang, S-Y, Lin, L-C, Hedman, T.P., The Influence of Exogenous Crosslinking and Compressive Creep Loading on Intradiscal Pressure, Biomech Model Mechanobiol. 9(5):533-538, 2010. Slusarewicz, P, Zhu, K, Hedman, T, Kinetic Characterization and Comparison of Various Protein Crosslinking Reagents Suitable for Tissue Engineering, J Mater Sci Mater Med., 21(4):1175-81, 2010. Slusarewicz, P., Zhu, K. and Hedman, T., Studies on the degradation of genipin in aqueous solution, Natural Products Communications, 5(12):1853-8, 2010. Slusarewicz, P., Zhu, K., Kirking, B., Toungate, J., Hedman, T., Optimization of Protein Crosslinking Formulations for the Treatment of Degenerative Disc Disease, Spine, 36(1):E7-13, 2011. Zhu, K, Slusarewicz, P, Hedman, T, Thermal Analysis Reveals Differential Effects of Various Crosslinkers on Bovine Annulus Fibrosis, J Orthop Res., 29(1):8-13, 2011. Popovich, J.M., Yau, D, Chuang, S-Y, Hedman, T., Exogenous Collagen Crosslinking of the Intervertebral Disc Restores Joint Stability following Lumbar Posterior Decompression Surgery, Spine, 36(12):1-6, 2011 .
Normal Aging, Disc Degeneration / Dehydration Annulus Overload / Nutritional Deficiency Bulges / Fissures / Cracks / Mechanical Insufficiency Disc Collapse / Herniations Nerve Root Compression / Facet Joint Pain
*Weber ‘94
x Harsh, nutritionally deficient environment of the disc led to DDD in the first place x “Degenerative discs are not able to support the added nutrient demands from increase in cellular activity or cell number…” – Jill Urban, PhD x Biological treatments offer no near- term effect, not appropriate as a stand-alone treatment
Vertebral Body (well vascularized) Intervertebral Disc (largely avascular)
Patent # Principal Claims US
10/230,671 Found in condition for allowance Mechanical degradation, disc, articular cartilage, load supporting collagenous tissue 7,435,722 Scoliosis and permeability, knee meniscus and articular cartilage 8,153,600 General deformity: kyphosis, listhesis, post-surgical; listed reagents; for increasing effectiveness of cell or cytokine treatments 8,022,101 Knee meniscus tear resistance; concentrations GP, PA, EDC, LO, TG, non-enzymatics 8,119,599 Tear resistance, prevention of expulsion of nucleus or nucleus implant; disc and knee meniscus, reagent concentrations 8,198,248 Formulation & composition of matter claims; 8,211,938 Treatment of annulus fibrosus against expulsion or extrusion of implanted device or material 8,283,322 Improved formulation and composition of matter claims 8,450,276 Increasing biological viability for regeneration of spinal discs 12/966,812 Found in condition for allowance Divisional: Mechanical degradation, disc, articular cartilage, load supporting collagenous tissue
Foreign
Australia 2002335683 Mechanical degradation, disc, articular cartilage, load supporting collagenous tissue Canada 2,458,821 Mechanical degradation, disc, articular cartilage, load supporting collagenous tissue Australia 2004268628 Spinal disc, scoliosis, permeability, knee meniscus, articular cartilage Japan 2006-524909 Spinal disc, scoliosis, permeability, knee meniscus, articular cartilage Canada 2,536,415 Crosslinking reagent for treating intervertebral disc disorders Korea Spinal disc, scoliosis, permeability, knee meniscus, articular cartilage
Exit Strategy #1: Early acquisition by spinal device company
$600k for 6 mo. FIM clinical trial + License fee, 300-650% ROI within 18 mo.
Todd Abruzzo, MD, John M Racadio, MD – spine surgeons & interventionalists
Exit Strategy #2: Acquisition after US market entry or IPO*
$6 million total investment, FIMs + clinicals for CE marking
Contact Tom Hedman for more information: thedman@intralinkspine.com
Available upon request Available upon request