 |
Please Note: The technology listed below is not available to the public at this time. This technology is in the early stage of research and requires further development before it is ready for the marketplace. The VA is currently in the process of identifying potential companies who may be interested in licensing and/or further developing the technology through Cooperative Research and Development Agreements (CRADA). Through cooperative research initiatives such as these, it is our hope and goal that commercial products will be fully developed and made available to benefit veterans and others.
VA TECHNOLOGY OPPORTUNITY BRIEF
Use of Clonal Human hNT2 Neuronal Cell Lines as 'Cellular Minipumps' to Treat Neurodegenerative Disorders and the Consequences of Brain and Spinal Cord Injuries
(02-106)
OPPORTUNITY:
The Department of Veterans Affairs (VA) is seeking a commercial partner through a Cooperative Research & Development Agreement (CRADA) to further develop a method of creating novel cell lines from a human NT2 parent line.
BACKGROUND:
This technology provides replacement or palliative therapy to victims of spinal cord injury (SCI) suffering chronic pain and/or spasticity. According to published reports, as many as 90 percent of persons with SCI have had chronic pain. Pain often results in a loss of function and interferes with work and social activities. Current pain treatment options, such as pharmacological agents and implantable mechanical pumps, have been associated with many unacceptable problems and side effects. This prompted the exploration of using transplanted neural cells and neural tissues to improve functional recovery in SCI patients.
TECHNOLOGY OVERVIEW:
The use of clonal human hNT2 neuronal cell lines as 'cellular minipumps' involves phenotypically pure subclones of hNT2 cells. These cells act as pumps to deliver neurotransmitters such as GABA, serotonin, or glycine when implanted near the central nervous system of persons suffering from neurodegenerative diseases or spinal cord injury (SCI). When implanted into a human, these cells produce neuroactive agents for the treatment of neural trauma and possibly neurodegenerative diseases. A process called subcloning was used to develop these novel human neural cell lines. Unique colonies of daughter cells are isolated from a naturally immortal human cell line called hNT2, so that the daughter colonies are different from each other and from the original parent hNT2 cell type. However, these new daughter cell lines retain the property of being naturally immortal when they are grown in the absence of retinoic acid (RA). In this condition, they multiply indefinitely and cultures may be frozen, stored, and restarted at any time. If the cells are treated with RA for a few weeks, they differentiate into human neurons. Such cells can be safely transplanted into the patient, with no danger of tumor formation, since they are irreversibly disimmortalized, no longer capable of division. In addition, they have characteristic features including the ability to make and secrete useful agents, such as the neurotransmitters serotonin (5HT), gamma aminobutyric acid (GABA) and glycine.
TECHNICAL MERIT:
This technology can be used to treat problems related to spinal cord injury, specifically chronic neuropathic pain and spasticity. Possible other applications of this technology may include benefit to victims of diabetic peripheral neuropathy pain, brain injury and the treatment of those affected by neurodegenerative diseases such as epilepsy, Alzheimer's, Parkinson's, and Huntington's diseases. hNT2 cells offer the following advantages over other neuronal graft approaches for the treatment of CNS trauma and/or degeneration:
- hNT2 cells are readily available and the potential for ethical issues is eliminated.
- Cells are of human origin and pluripotent.
- Cells can be easily grown and differentiated.
- Cells are capable of long term survival following implantation in humans and other animals.
- Cells are transfectable and selectable.
- Cells have been shown to integrate into nervous tissue after implantation.
- The subcloning method will produce novel cell lines that are more phenotypically and morphologically homogeneous than currently available cell lines.
RECENT RELEVANT PUBLICATIONS:
- Eaton MJ, Pearse DD, McBroom J, Berrocal YA (2008) The combination of human neuronal serotonergic cell implants and environmental enrichment after contusive SCI improves motor recovery over each individual strategy. Behav Brain Res (in press).
- Eaton MJ, Wolfe SQ, and Gomez-Marin, O. (2008) Clinical Feasibility for Cell Therapy Utilizing a Human Neuronal Cell Line to Treat Neuropathic Pain-like Behaviors following SCI. J Rehab Res Develop (in press).
- Wolfe SQ, Cumberbatch NMA, Menendez I, Martinez M, Eaton MJ (2007) Intrathecal transplantation of a human neuronal cell line for the treatment of neuropathic pain in a spinal cord injury model. Clinical Neurosurgery 54: 220-225.
- Wolfe SQ, Salzberg M, Cumberbatch NMA, Garg M, Furst C, Martinez M, Hernandez M, Reimers R, Berrocal Y, Eaton MJ (2007) Optimizing the transplant dose of a human neuronal cell line to treat SCI pain in the rat. Neurosci Lttrs. 414(2):121-5.
- Eaton MJ, Wolf SQ, Martinez M, Hernandez M, Furst C, Huang J, Frydel B, Gómez-Marin O (2007) Subarachnoid transplant of a human neuronal cell line attenuates allodynia and hyperalgesia after excitotoxic SCI in the rat J Pain 8(1):33-50.
PATENT STATUS:
Provisional patent filed on April 17, 2003 (60/463,315)
PCT patent application was filed on July 17, 2003 (PCT/US03/19559)
A US non-provisional application was filed July 17, 2003 (10/533,291).
FOR MORE INFORMATION CONTACT:
Ken Levin, Ph.D.
Technology Transfer Specialist
Technology Transfer Program
Department of Veterans Affairs
Office of Research & Development (12TT)
810 Vermont Avenue, NW
Washington, DC 20420
Phone: 202-461-1713
Fax: 202-254-0473
E-mail: Ken.levin@va.gov
Last Updated - August 6, 2008