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Neurosurgery

Kurpad Lab

Dr. Shekar Kurpad

Spinal cord injury (SCI) is a relatively frequent event; estimates suggest that 12,500 new cases of SCI occur every year in the US alone. In the US, approximately 276,000 persons live with SCI, which has a huge impact on their lives and families, and has tremendous socioeconomic and medical costs. The main causes for SCI are motor vehicle accidents (38%), falls (30%), acts of violence (14%), and sports injuries (9%) (National SCI Database).

The type and degree of disability that is caused by SCI is determined by the location and extent of the injury. Spinal cord tissue is damaged in the injury process and this damage occurs in two steps. The initial damage, the primary injury, is caused by the mechanical trauma to the spinal cord during the accident. This is followed by the secondary injury, which is caused by a number of events, including hemorrhage and inflammation. While acute inflammation is observed in all tissues as a response to injury and is an important prerequisite for the healing process, prolonged and unresolved inflammation, as it is present after SCI, strongly contributes to the tissue damage. Immune cells in the tissue produce factors that maintain and stimulate the inflammatory response and produce factors that contribute to tissue damage.

Red blood cells (RBCs), which are present in the spinal cord tissue due to the hemorrhage, are taken up by phagocytic cells like macrophages. This can result in increased production of pro-inflammatory cytokines and chemokines, factors that activate immune cells. Previous experiments have shown the relevance of some of these factors after SCI. For example, the absence of one of these cytokines, TNF, leads to a better recovery in mice after SCI and reduces inflammatory activation of cells at the injury site. However, these extent of these results suggests that other factors also contribute to the tissue damage.

We are now attempting to investigate further mechanisms contributing to the secondary tissue damage, including other cytokines and chemokines which may play a role after SCI. We aim to modulate these and investigate the effect on recovery after SCI.

Ultimately, our goal is a translational treatment approach to reduce secondary damage after injury and to improve the outcome and quality of life after SCI. In summary, the broad goal of my research is to investigate and modulate the inflammatory tissue response after spinal cord injury (SCI) with the aim to reduce the secondary damage and thereby to improve the functional outcome after SCI.


Ongoing Studies

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AST-OPC1-02: A Long-term Follow-up Study of Subjects with Cervical Spinal Cord Injuries Who Received AST-OPC1 in Protocol AST-OPC1-01
The purpose of this study is to monitor long-term safety in subjects with cervical SCI who received injections of AST-OPC1 under the study protocol AST-OPC1-01.
INSPIRE 2.0: Randomized, Controlled, Single-blind Study of Probable Benefit of the Neuro-Spinal Scaffold (TM) for Safety and Neurologic Recovery in Subjects with Complete Thoracic AIS A Spinal Cord Injury as Compared to Standard of Care
The purpose of this study is to evaluate whether the Scaffold is safe and demonstrates probable benefit for the treatment of complete T2-T12 spinal cord injury as compared to standard of care open spine surgery.
MT-3921-A01: A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of MT-3921 in Subjects with Acute Traumatic Cervical Spinal Cord Injury
The purpose of this study is to compare the efficacy and safety of intravenous (IV) infusions of MT-3921 to placebo in subjects with acute traumatic cervical spinal cord injury.
ELASCI: A Randomized, Double-Blind, Placebo-Controlled Proof of Concept Study to Assess the Safety and Efficacy of Elezanumab in Acute Traumatic Cervical Spinal Cord Injury
The purpose of this study is to see if elezanumab is safe and to assess change in Upper Extremity Motor Score (UEMS) in participants with acute traumatic cervical SCI.

Completed Studies

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MT-3921-G01: A study to Investigate the Safety, Tolerability, Pharmacokinetics of Single Ascending Dose of MT-3921 in Subjects with Acute Spinal Cord Injury
The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of MT-3921 in spinal cord injuries.
RISCIS: A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded, Trial of Efficacy and Safety of Riluzole in Acute Spinal Cord Injury
The purpose of this study was to evaluate the efficacy and safety of Riluzole in the treatment of patients with acute SCI.
AST-OPC1-01: A Phase 1/2a Dose Escalation Study of AST-OPC1 in Subjects with Subacute Cervical Spinal Cord Injury
The purpose of this study was to evaluate the safety of cross sequential escalating doses of AST-OPC1 administered among five cohorts at a single time-point between 21- and 42-days post injury, inclusively, to subjects with subacute cervical spinal cord injuries (SCI).
The INSPIRE Study: Probable Benefit of the Neuro-Spinal Scaffold for Treatment of AIS A Thoracic Acute Spinal Cord Injury
The purpose of this study was to evaluate the safety and probable benefit of the poly(lactic-co-glycolic acid)-b-poly(L-lysine) Scaffold ("Scaffold") in subjects with thoracic AIS A traumatic spinal cord injury at neurological level of injury of T2-T12.
A Double-Blind, Placebo-Controlled Study of AC105 in patients with Acute Traumatic Spinal Cord Injury
This was a phase 2 double-blind, randomized, placebo-controlled study to determine the safety, tolerability, and potential activity of AC105.
A Phase 1 Safety Study of GRNOPC1 in Patients with Neurologically Complete, Subacute, Spinal Cord Injury
The purpose of the study was to evaluate the safety of GRNOPC1 administered at a single time-point between 7- and 14-days post injury, inclusive, to patients with neurologically complete spinal cord injuries (SCI).
Study of Human Central Nervous System (CNS) Stem Cell Transplantation in Cervical Spinal Cord Injury
The purpose of this study was to evaluate the safety and efficacy of human central nervous system stem cell transplantation into patients with traumatic injury in the cervical region of the spinal cord.

Recent Publications

  • (Koch KM, Nencka AS, Kurpad S, Budde MD.) J Neurotrauma. 2024 Sep;41(17-18):2125-2132 PMID: 38251658 SCOPUS ID: 2-s2.0-85190264996 01/22/2024

  • (Davies BM, Yang X, Khan DZ, Mowforth OD, Touzet AY, Nouri A, Harrop JS, Aarabi B, Rahimi-Movaghar V, Kurpad SN, Guest JD, Tetreault L, Kwon BK, Boerger TF, Rodrigues-Pinto R, Furlan JC, Chen R, Zipser CM, Curt A, Milligan J, Kalsi-Rayn S, Sarewitz E, Sadler I, Blizzard T, Treanor C, Anderson D, Fallah N, Hazenbiller O, Salzman C, Zimmerman Z, Wandycz AM, Widdop S, Reeves M, Raine R, Ryan SK, Malone A, Gharooni A, Wilson JR, Martin AR, Fehlings MG, McNair AGK, Kotter MRN, AO SPINE RECODE-DCM Steering Committee and AO Spine RECODE DCM Community.) PLoS Med. 2024 Aug;21(8):e1004447 PMID: 39173109 PMCID: PMC11379399 SCOPUS ID: 2-s2.0-85201785269 08/22/2024

  • (Lee S, Schmit BD, Kurpad SN, Budde MD.) NMR Biomed. 2024 Jun;37(6):e5115 PMID: 38355219 PMCID: PMC11078600 SCOPUS ID: 2-s2.0-85185526294 02/15/2024

  • (Fehlings MG, Tetreault LA, Hachem L, Evaniew N, Ganau M, McKenna SL, Neal CJ, Nagoshi N, Rahimi-Movaghar V, Aarabi B, Hofstetter CP, Wengel VT, Nakashima H, Martin AR, Kirshblum S, Rodrigues Pinto R, Marco RAW, Wilson JR, Kahn DE, Newcombe VFJ, Zipser CM, Douglas S, Kurpad SN, Lu Y, Saigal R, Samadani U, Arnold PM, Hawryluk GWJ, Skelly AC, Kwon BK.) Global Spine J. 2024 Mar;14(3_suppl):174S-186S PMID: 38526922 PMCID: PMC10964895 03/25/2024

  • (Davies BM, Khan DZ, Barzangi K, Ali A, Mowforth OD, Nouri A, Harrop JS, Aarabi B, Rahimi-Movaghar V, Kurpad SN, Guest JD, Tetreault L, Kwon BK, Boerger TF, Rodrigues-Pinto R, Furlan JC, Chen R, Zipser CM, Curt A, Milligan J, Kalsi-Rayn S, Sarewitz E, Sadler I, Widdop S, Fehlings MG, Kotter MRN.) Global Spine Journal. March 2024;14(2):503-512 SCOPUS ID: 2-s2.0-85133336136 03/01/2024

  • (Hachem LD, Zhu M, Aarabi B, Davies B, DiGiorgio A, Evaniew N, Fehlings MG, Ganau M, Graves D, Guest J, Ha Y, Harrop J, Hofstetter C, Koljonen P, Kurpad S, Marco R, Martin AR, Nagoshi N, Nouri A, Rahimi-Movaghar V, Rodrigues-Pinto R, Wengel Vt, Tetreault L, Kwon B, Wilson JR.) Global Spine Journal. March 2024;14(2):535-545 SCOPUS ID: 2-s2.0-85138317004 03/01/2024

  • (Fehlings MG, Moghaddamjou A, Harrop JS, Stanford R, Ball J, Aarabi B, Freeman BJC, Arnold PM, Guest JD, Kurpad SN, Schuster JM, Nassr A, Schmitt KM, Wilson JR, Brodke DS, Ahmad FU, Yee A, Ray WZ, Brooks NP, Wilson J, Chow DS, Toups EG, Kopjar B.) J Neurotrauma. 2023 Sep;40(17-18):1878-1888 PMID: 37279301 PMCID: PMC10460693 SCOPUS ID: 2-s2.0-85166327228 06/06/2023

  • (Hussain O, Kaushal M, Agarwal N, Kurpad S, Shabani S.) Life (Basel). 2023 Aug 03;13(8) PMID: 37629537 PMCID: PMC10455833 SCOPUS ID: 2-s2.0-85168918079 08/26/2023

  • (Davies B, Brannigan J, Mowforth OD, Khan D, McNair AGK, Tetreault L, Sadler I, Sarewitz E, Aarabi B, Kwon B, Gronlund T, Rahimi-Movaghar V, Zipser CM, Hutchinson PJ, Kurpad S, Harrop JS, Wilson JR, Guest JD, Fehlings MG, Kotter MRN.) BMJ Open. 2023 Jul 18;13(7):e064296 PMID: 37463815 PMCID: PMC10357680 SCOPUS ID: 2-s2.0-85165517288 07/19/2023

  • (Fehlings M, Moghaddamjou A, Harrop J, Ball J, Arnold P, Guest J, Kurpad S, Schuster J, Nassr A, Wilson J, Brodke D, Ray W, Kopjar B.) Spine Journal. September 2023;23(9):S36 SCOPUS ID: 2-s2.0-85193486652 09/01/2023

  • (Aarabi B, Neal CJ, Hersh DS, Harrop JS, Fehlings MG, Toups EG, Guest JD, Ugiliweneza B, Akhtar-Danesh N, Kurpad SN, Grossman RG.) Neurotrauma Rep. 2023;4(1):375-383 PMID: 37350794 PMCID: PMC10282967 06/23/2023

  • (Koch KM, Nencka AS, Klein A, Wang M, Kurpad S, Vedantam A, Budde M.) Front Neurol. 2023;14:1172833 PMID: 37273696 PMCID: PMC10236479 SCOPUS ID: 2-s2.0-85161052826 06/05/2023

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