Novel Method To Differentiate Human Embryonic Stem Cells Into Dopaminergic Nerve Cells

E-176-2008

Keywords: Parkinson's Disease, Neurological Diseases

Background:
The National Institute on Drug Abuse''s Development and Plasticity Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel methods to differentiate human embryonic stem cells into dopaminergic nerve cells.

Technology:
Neurodegenerative disorders encompass a range of debilitating conditions including Parkinson''s disease, Alzheimer's disease, and Huntington''s disease.  The primary cause of motor dysfunction for Parkinson''s disease has been linked to degeneration of dopaminergic neurons in specific areas of the brain.  Transplantation of dopaminergic neurons in affected areas of the brain in late stage Parkinson''s disease has potential clinical utility in human patients.  However, fetal nigral transplantation therapy generally requires human tissue from at least 3-5 embryos to obtain a clinically reliable improvement in the patient, thus demonstrating a need for a larger and more reliable source of dopaminergic cells.  Other techniques for generating dopaminergic neurons from human embryonic stem cells (hESCs) are either inefficient, require the use of animal-derived cells or products, or involve complex and lengthy procedures.

This invention describes a novel combination of soluble proteins which, when used under appropriate cell culture conditions, causes hESCs to differentiate into dopaminergic nerve cells.  This invention potentially provides a source of sufficient dopaminergic cells not only for the clinical transplantation of dopaminergic tissue, but also for in vitro studies of human cells useful for pharmaceutical screens related to neurodegenerative disorders and substance abuse.

Potential Commercial Applications/Possible Markets Identified:

• Human dopaminergic cell source for neuronal transplantation, with potential clinical application to Parkinson''s disease and possibly other neurodegenerative disorders.
• Human dopaminergic cell source for in vitro models for pharmaceutical screens relevant to neurodegenerative disorders and substance abuse.

Main Advantages of Technology/Invention:

• Ability to differentiate human embryonic stem cells (hESCs) into dopaminergic nerve cells with very high efficiency.
• The protocol is technically simple and rapid.
• In contrast to previous protocols, this method does not require the use of animal-derived cells or products, selection of neural precursor cells, retinoic acid or multiple treatment phases.

R&D Status: Pre-clinical, in-vitro discovery

Further R&D Needed: 
For transplantation in human subjects, a great deal of additional development is needed. It would be necessary to:

• Develop a differentiation model based on the current discoveries that will comply with GMP (good manufacturing practices) regulations
• Ensure that no undifferentiated cells remain in the mixture, that the method could be applied to various lines of human embryonic stem cells, and that differentiated cells do not form tumors when transplanted into the brain.  The procedure would need to be  optimized for transplantation, by varying parameters such as concentrations of growth factors used.
• Determine efficacy and safety in rodent and sub-human primate transplantation models.

In contrast, cells produced using the methods described in this invention can be used as an in vitro model for drug testing without further development.

IP Status:

• U.S. Provisional Application No. 61/199,652 filed 18 Nov 2008

Contact Information:
Vio Conley, M.S.
NCI Technology Transfer Center
Tel: 240-276-5531
Email: conleyv@mail.nih.gov

Please reference advertisement #912

Revised 6/29/2009

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