In spite of extensive research on the pathogenesis of MS, no effective therapy is available to halt this demyelinating disease process. In MS, myelin repair is generally insufficient despite the relative survival of oligodendrocytes within the plaques and the recruitment of oligodendrocyte precursors. Promoting remyelination, therefore, appears to be a crucial therapeutic challenge. While neurotrophins (NGF, NT-3, NT-4/5, and BDNF) and glial cell line-derived neurotrophic factor (GDNF)-related factors (GDNF, neurturin) do not increase myelinogenesis, ciliary neurotrophic factor (CNTF) induces a strong promyelinating effect. Therefore, increasing the level of CNTF in the CNS is an important step in repairing axonal damage in MS. Although gene manipulation and stereotaxic injection of CNTF into the brain are available options, it seems from the therapeutic angle, the best option is to stimulate/induce the production of CNTF within the CNS of patients with MS. Is it really possible? Our exciting preliminary results demonstrate that it is possible by a natural compound. Cinnamon is a natural spice and flavoring material used for centuries throughout the world. We have found that oral feeding of ground cinnamon increases the level of CNTF in the CNS of normal mice and mice with experimental allergic encephalomyelitis (EAE);an animal model of MS. Consistently, cinnamon metabolite sodium benzoate (NaB) also increases the expression of CNTF in astrocytes. Therefore, from the academic angle, we have planned experiments in Specific aim I to investigate molecular mechanisms by which cinnamon metabolite NaB increases CNTF in astrocytes.
Specific aim II has been devoted for therapeutic purposes. Here we would like to delineate the efficacy of orally administered cinnamon in inhibiting the disease process of EAE.
Specific aim III has been enshrined to delineate if cinnamon requires CNTF to inhibit the disease process of EAE. If our study becomes successful, it will describe a novel myelinotrophic activity of cinnamon and ~ 1 teaspoonful of ground cinnamon per day may help MS patients to manage the disease process bringing down the drug cost to <$10 per month for each patient.

Public Health Relevance

In spite of extensive research on the pathogenesis of MS, no effective therapy is available to halt this demyelinating disease process. Studies proposed from various angles in this grant application will delineate the efficacy of orally administered cinnamon in increasing oligodendroglial trophic factor CNTF in the CNS and inhibiting the disease process of EAE, an animal model of MS. If our study becomes successful, ~1 teaspoonful of ground cinnamon per day with tea, milk, cocoa, or honey may help MS patients to manage the disease process.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT006681-04
Application #
8699146
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Pontzer, Carol H
Project Start
2011-06-01
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$363,750
Indirect Cost
$121,250
Name
Rush University Medical Center
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068610245
City
Chicago
State
IL
Country
United States
Zip Code
60612
Modi, Khushbu K; Rangasamy, Suresh B; Dasarathi, Sridevi et al. (2016) Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement. J Neuroimmune Pharmacol 11:693-707
Kundu, Madhuchhanda; Mondal, Susanta; Roy, Avik et al. (2016) Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Enriches Regulatory T Cells via STAT6-Mediated Upregulation of TGF-β. J Immunol 197:3099-3110
Ghosh, Arunava; Pahan, Kalipada (2016) PPARα in lysosomal biogenesis: A perspective. Pharmacol Res 103:144-8
Corbett, Grant T; Gonzalez, Frank J; Pahan, Kalipada (2015) Activation of peroxisome proliferator-activated receptor α stimulates ADAM10-mediated proteolysis of APP. Proc Natl Acad Sci U S A 112:8445-50
Modi, Khushbu K; Jana, Malabendu; Mondal, Susanta et al. (2015) Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Upregulates Ciliary Neurotrophic Factor in Astrocytes and Oligodendrocytes. Neurochem Res 40:2333-47
Roy, Avik; Jana, Malabendu; Kundu, Madhuchhanda et al. (2015) HMG-CoA Reductase Inhibitors Bind to PPARα to Upregulate Neurotrophin Expression in the Brain and Improve Memory in Mice. Cell Metab 22:253-65
Modi, Khushbu K; Roy, Avik; Brahmachari, Saurabh et al. (2015) Cinnamon and Its Metabolite Sodium Benzoate Attenuate the Activation of p21rac and Protect Memory and Learning in an Animal Model of Alzheimer's Disease. PLoS One 10:e0130398
Ghosh, Arunava; Jana, Malabendu; Modi, Khushbu et al. (2015) Activation of peroxisome proliferator-activated receptor α induces lysosomal biogenesis in brain cells: implications for lysosomal storage disorders. J Biol Chem 290:10309-24
Pahan, Kalipada (2015) Prospects of Cinnamon in Multiple Sclerosis. J Mult Scler (Foster City) 2:1000149
Roy, Avik; Pahan, Kalipada (2015) PPARα signaling in the hippocampus: crosstalk between fat and memory. J Neuroimmune Pharmacol 10:30-4

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