This is a Translational Research Proposal to develop glial restricted progenitor cells (GRPs) as a therapeutic for the treatment of Amyotropic Lateral Sclerosis (ALS;also known as Lou Gehrig's Disease). ALS is a neurodegenerative disease that affects both upper and lower motor neurons. This disease is characterized by the progressive deterioration and loss of motor neurons.The loss of nerve stimulus to specific muscles results in atrophy and progressive weakness that leads to paralysis. The length of survival in most patient populations that have been evaluated is 3 to 5 years. No cure has yet been found for ALS. In an animal model of ALS it has been shown that GRPs slow disease progression and improve respiratory function. The animal cells used in these experiments are not compatible with human dosing. This proposal aims to develop the homologous human derived GRPs for therapeutic use in ALS.
The aims of this proposal are to 1) demonstrate that human GRPs behave similarly to rat GRPs in an animal model of ALS, 2) develop the antibody used to purify human GRPs to the specification required for its use in cellular therapeutic production 3) produce human GRPs under Good Laboratory Practices (GLP) conditions required for animal safety studies and 4) demonstrate that human GRPs are safe, non-toxic, and non-tumorigenicin animal models.
Aims 1, 4 and 5 will be achieved by implanting human GRPs into the spinal cord of relevant animal models and assessing their effects at both the cellular and behavioral levels.
Aim 2 will be achieved by standard antibody production and purification methods, while Aim 3 will entail cellular production by standard cellular purification and culturingtechniques performed according to GLP standards. Successful completion of these studies will form the basis of anInvestigational New Drug (IND) application with the FDA seeking to conduct a clinical trial in ALS.

Public Health Relevance

There is no cure for Amyotrophic Lateral Sclerosis (ALS), a disease in which nerve cells that control muscle function die resulting in death within 3-5 years. This proposal is designed to develop a cellular therapy for the treatment of this devastating disease by performing the studies required to begin a clinical trial of this novel therapeutic approach. If successful, this proposal will lead to a therapy which will restore normal function to the effected nerve cells which in turn will slow or halt the progression of the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS062713-04
Application #
8145663
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Gubitz, Amelie
Project Start
2009-07-01
Project End
2015-12-31
Budget Start
2012-07-01
Budget End
2013-12-31
Support Year
4
Fiscal Year
2012
Total Cost
$1,317,241
Indirect Cost
$483,363
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Lepore, Angelo C; O'Donnell, John; Kim, Andrew S et al. (2011) Human glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 mouse model of ALS. PLoS One 6:e25968