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Chimeric proteins for the treatment of spinal cord injury

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
76416
Program Year/Program:
2005 / SBIR
Agency Tracking Number:
NS050894
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
Acorda Therapeutics, Inc.
15 Skyline Drive Hawthorne, NY 10532
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2005
Title: Chimeric proteins for the treatment of spinal cord injury
Agency: HHS
Contract: 1R43NS050894-01A1
Award Amount: $153,151.00
 

Abstract:

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) inflicts trauma to the cells and tissues of the central nervous system and causes a severe and debilitating condition in the individual. Following SCI, limited regeneration of injured neurons results in permanent disability characterized by some loss of sensation, paralysis and autonomic dysfunction. One reason that neurons fail to regenerate is their inability to traverse the glial scar that develops following SCI. This glial scar contains extracellular matrix molecules including chondroitin sulfate proteoglycans (CSPGs). In vitro studies show that neurons fail to extend processes over CSPG coated surfaces, while in vivo data correlate failure of regeneration with areas of CSPG expression. Chondroitinase ABCI is a bacterial enzyme that catalyzes the degradation of chondroitin sulfate carbohydrate chains such as those found on CSPG. Chondroitinase treatment was found to improve functional outcome following surgical lesion of the dorsal column / cortico-spinal pathways in rodents. In addition, Chondroitinase was found to restore a period of plasticity in the visual cortex of rodents. We have recently demonstrated that Chondroitinase ABC I treatment improves open-field locomotor function and autonomic function in a contusion SCI model. Although the effects in animal models are significant, clinically relevant improvements in neurological function following SCI may require combinatorial therapies. For example, Chondroitinase treatment may be combined with an inhibitor of NOGO such as the decoy NOGO receptor (NgR) to promote regeneration. The objective of this grant proposal is to combine Chondroitinase with NgR at the genetic level to create a bi-functional therapeutic protein (Chase-NgR). In addition to providing combinatorial therapy with a single drug the affinity of the NgR for myelin associated inhibitors would confer a targeting mechanism to Chase-NgR wherein Chondroitinase treatment is focused on inhibitor rich regions in the CNS. In addition, we have shown that Chondroitinase facilitates diffusion into the CMS presumably by creating pathways for diffusion via digestion of CSPG. Therefore, Chondroitinase segment of Chase-NgR may promote diffusion of the NgR into the parenchyma of the CNS to a much greater extent than can be achieved without CSPG digestion. These studies will provide justification for a Phase II grant to fund further development of Chase-NgR as a therapeutic for SCI.

Principal Investigator:

Anthony O. Caggiano
9143474300
TCAGGIANO@ACORDA.COM

Business Contact:

Ron Cohen
9143474300
RCOHEN@ACORDA.COM
Small Business Information at Submission:

Acorda Therapeutics, Inc.
15 Skyline Drive Hawthorne, NY 10532

EIN/Tax ID: 133831168
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No