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 #
5R01AT006681-03
Application #
8675192
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
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
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
Jana, Malabendu; Mondal, Susanta; Jana, Arundhati et al. (2014) Interleukin-12 (IL-12), but not IL-23, induces the expression of IL-7 in microglia and macrophages: implications for multiple sclerosis. Immunology 141:549-63
Khasnavis, Saurabh; Pahan, Kalipada (2014) Cinnamon treatment upregulates neuroprotective proteins Parkin and DJ-1 and protects dopaminergic neurons in a mouse model of Parkinson's disease. J Neuroimmune Pharmacol 9:569-81
Roy, Avik; Pahan, Kalipada (2013) Ankyrin repeat and BTB/POZ domain containing protein-2 inhibits the aggregation of alpha-synuclein: implications for Parkinson's disease. FEBS Lett 587:3567-74
Modi, Khushbu K; Sendtner, Michael; Pahan, Kalipada (2013) Up-regulation of ciliary neurotrophic factor in astrocytes by aspirin: implications for remyelination in multiple sclerosis. J Biol Chem 288:18533-45
Corbett, Grant T; Roy, Avik; Pahan, Kalipada (2013) Sodium phenylbutyrate enhances astrocytic neurotrophin synthesis via protein kinase C (PKC)-mediated activation of cAMP-response element-binding protein (CREB): implications for Alzheimer disease therapy. J Biol Chem 288:8299-312
Jana, Malabendu; Pahan, Kalipada (2013) Down-regulation of Myelin Gene Expression in Human Oligodendrocytes by Nitric Oxide: Implications for Demyelination in Multiple Sclerosis. J Clin Cell Immunol 4:
Jana, Arundhati; Modi, Khushbu K; Roy, Avik et al. (2013) Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol 8:739-55
Roy, Avik; Jana, Malabendu; Corbett, Grant T et al. (2013) Regulation of cyclic AMP response element binding and hippocampal plasticity-related genes by peroxisome proliferator-activated receptor *. Cell Rep 4:724-37
Khasnavis, Saurabh; Pahan, Kalipada (2012) Sodium benzoate, a metabolite of cinnamon and a food additive, upregulates neuroprotective Parkinson disease protein DJ-1 in astrocytes and neurons. J Neuroimmune Pharmacol 7:424-35