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PageThe INR has invented and pioneered unique, anti-TNF therapeutic approaches for a variety of medical disorders with enormous unmet need, including Alzheimer's disease and various forms of neuropathic pain, including sciatica and cervical radiculopathy[1-9].
The INR has published its findings in multiple, peer-reviewed medical journals, including BMC Neurology, Current Alzheimer Research, Clinical Therapeutics, Drug Discovery Today, and Current Medical Research and Opinion. INR publications, findings, and research have advanced the science of neurology, dementia, and spine medicine, and have been cited and discussed by physicians and scientists from academic centers around the world. In 2008 alone there were more than 45 scientific citations to INR publications, including in Nature Clinical Practice Neurology and F1000 Biology.
The INR has presented its scientific findings at multiple U.S. and international medical and scientific conferences, including the Karolinska Institute in Sweden; the 2008 Drug Repositioning Summit in Boston; the International Conference on Alzheimer's Disease in Chicago; the 7th Annual Alzheimer's Drug Discovery Conference in New York; the 2008 Best Practices in the Continuum of Care: Advances in Alzheimer's Disease Management conference at the University of Arkansas Medical Sciences in Little Rock, Arkansas; and, in 2009, the 3rd International Restauracion Neurologica Conference in Havana, Cuba. Invited presentations at the World Pharmaceutical Congress in Philadelphia in June 2009 and the 5th Modern Drug Discovery Conference in October 2009 in San Diego are scheduled.
The INR has performed collaborative research with scientists from Stanford University School of Medicine and the University of British Columbia in Vancouver.
The central role of excess TNF in the pathogenesis of Alzheimer's disease and sciatica is now supported by multiple scientific studies from academic centers around the world, including genetic, basic science, epidemiologic, and clinical studies[11, 13-33] (reviewed in [2, 5, 6]). The perispinal etanercept treatment method for sciatica invented by Edward Tobinick MD in 2001 (U.S. patent 6,419,944) has recently (May 2009) received further robust scientific support due to publication of a favorable randomized, double-blind, placebo-controlled clinical trial conducted at the Walter Reed Army Medical Center [34], and a new basic science study conducted by scientists from UC San Diego[35].
Edward Tobinick MD, Director of the INR, is an Assistant Clinical Professor of Medicine at the David Geffen School of Medicine at UCLA and a member of the Editorial Board of the Journal of Neuroinflammation. In 2009 he has been an invited expert reviewer for the medical journals Neuroscience, Experimental Neurology, and Brain Research. Dr. Tobinick is a frequent invited speaker at international medical and scientific conferences, and the author of mutiple, peer-reviewed articles in the scientific and medical literature. Dr. Tobinick is the inventor of perispinal and epidural etanercept for neurological disorders, including Alzheimer's disease, other forms of dementia, sciatica, and disc-related back and neck pain.
Please download the full-text of the following independent, published scientific opinion: Griffin WS. Perispinal etanercept: Potential as an Alzheimer therapeutic. J Neuroinflammation. 2008 Jan 10;5(1):3. [download free full-text PDF].
Please click on each image
below to download a summary or full-text copy of the selected
scientific article:
References
1. Tobinick, E.L. and H. Gross,
Rapid improvement in verbal fluency and aphasia following perispinal
etanercept in Alzheimer's disease. BMC Neurol, 2008. 8:
p. 27.
2. Tobinick, E.L. and H. Gross, Rapid cognitive improvement
in Alzheimer's disease following perispinal etanercept administration.
J Neuroinflammation, 2008. 5: p. 2.
3. Tobinick, E., Perispinal etanercept produces rapid improvement
in primary progressive aphasia: identification of a novel, rapidly
reversible TNF-mediated pathophysiologic mechanism. Medscape
J Med, 2008. 10(6): p. 135.
4. Griffin, W.S., Perispinal etanercept: potential as an Alzheimer
therapeutic. J Neuroinflammation, 2008. 5: p. 3.
5. Tobinick, E., Perispinal etanercept for treatment of Alzheimer's
disease. Curr Alzheimer Res, 2007. 4(5): p. 550-2.
6. Tobinick, E., H. Gross, A. Weinberger, and H. Cohen, TNF-alpha
modulation for treatment of Alzheimer's Disease: A six month pilot
study. Alzheimer's & Dementia: The Journal of the Alzheimer's
Association, 2006. 2(3): p. S364-S365.
7. Tobinick, E., H. Gross, A. Weinberger, and H. Cohen, TNF
Modulation for Treatment of Alzheimer's Disease: A 6-month Pilot
Study. Medscape General Medicine: Neurology, 2006. 8(2):
p. 25f.
8. Tobinick, E. and S. Davoodifar, Efficacy of etanercept delivered
by perispinal administration for chronic back and/or neck disc-related
pain: a study of clinical observations in 143 patients. Curr
Med Res Opin, 2004. 20(7): p. 1075-85.
9. Tobinick, E.L. and S. Britschgi-Davoodifar, Perispinal TNF-alpha
inhibition for discogenic pain. Swiss Med Wkly, 2003. 133(11-12):
p. 170-7.
10. Youn, D.H., H. Wang, and S.J. Jeong, Exogenous tumor necrosis
factor-alpha rapidly alters synaptic and sensory transmission
in the adult rat spinal cord dorsal horn. J Neurosci Res,
2008.
11. Rowan, M.J., I. Klyubin, Q. Wang, N.W. Hu, and R. Anwyl, Synaptic
memory mechanisms: Alzheimer's disease amyloid beta-peptide-induced
dysfunction. Biochem Soc Trans, 2007. 35(Pt 5): p.
1219-23.
12. Wang, Y., Modification of synaptic plasticity by TNF and
sphingomyelinase: Implications for cognitive impairment in AD,
in ICAD 2008: Molecular mechanisms of neurodegeneration; synaptic
disruption. 2008: Chicago.
13. Perry, R.T., J.S. Collins, H. Wiener, R. Acton, and R.C. Go,
The role of TNF and its receptors in Alzheimer's disease.
Neurobiol Aging, 2001. 22(6): p. 873-83.
14. Tarkowski, E., N. Andreasen, A. Tarkowski, and K. Blennow,
Intrathecal inflammation precedes development of Alzheimer's
disease. J Neurol Neurosurg Psychiatry, 2003. 74(9):
p. 1200-5.
15. Laws, S.M., R. Perneczky, S. Wagenpfeil, U. Muller, H. Forstl,
R.N. Martins, A. Kurz, and M. Riemenschneider, TNF polymorphisms
in Alzheimer disease and functional implications on CSF beta-amyloid
levels. Hum Mutat, 2005. 26(1): p. 29-35.
16. Pickering, M., D. Cumiskey, and J.J. O'Connor, Actions
of TNF-alpha on glutamatergic synaptic transmission in the central
nervous system. Exp Physiol, 2005. 90(5): p. 663-70.
17. Wang, Q., J. Wu, M.J. Rowan, and R. Anwyl, Beta-amyloid
inhibition of long-term potentiation is mediated via tumor necrosis
factor. Eur J Neurosci, 2005. 22(11): p. 2827-32.
18. Chiarini, A., I. Dal Pra, J.F. Whitfield, and U. Armato, The
killing of neurons by beta-amyloid peptides, prions, and pro-inflammatory
cytokines. Ital J Anat Embryol, 2006. 111(4): p. 221-46.
19. Ramos, E.M., M.T. Lin, E.B. Larson, I. Maezawa, L.H. Tseng,
K.L. Edwards, G.D. Schellenberg, J.A. Hansen, W.A. Kukull, and
L.W. Jin, Tumor necrosis factor alpha and interleukin 10 promoter
region polymorphisms and risk of late-onset Alzheimer disease.
Arch Neurol, 2006. 63(8): p. 1165-9.
20. Csiszar, A., N. Labinskyy, K. Smith, A. Rivera, Z. Orosz,
and Z. Ungvari, Vasculoprotective effects of anti-tumor necrosis
factor-alpha treatment in aging. Am J Pathol, 2007. 170(1):
p. 388-98.
21. Tweedie, D., K. Sambamurti, and N.H. Greig, TNF-alpha Inhibition
as a Treatment Strategy for Neurodegenerative Disorders: New Drug
Candidates and Targets. Curr Alzheimer Res, 2007. 4(4):
p. 375-8.
22. De, A., J.M. Krueger, and S.M. Simasko, Glutamate induces
the expression and release of tumor necrosis factor-alpha in cultured
hypothalamic cells. Brain Res, 2005. 1053(1-2): p.
54-61.
23. Edwards, M.M. and S.R. Robinson, TNF alpha affects the
expression of GFAP and S100B: implications for Alzheimer's disease.
J Neural Transm, 2006.
24. Janelsins, M.C., M.A. Mastrangelo, S. Oddo, F.M. LaFerla,
H.J. Federoff, and W.J. Bowers, Early correlation of microglial
activation with enhanced tumor necrosis factor-alpha and monocyte
chemoattractant protein-1 expression specifically within the entorhinal
cortex of triple transgenic Alzheimer's disease mice. J Neuroinflammation,
2005. 2: p. 23.
25. Jekabsone, A., P.K. Mander, A. Tickler, M. Sharpe, and G.C.
Brown, Fibrillar beta-amyloid peptide Abeta1-40 activates microglial
proliferation via stimulating TNF-alpha release and H2O2 derived
from NADPH oxidase: a cell culture study. J Neuroinflammation,
2006. 3: p. 24.
26. Medeiros, R., R.D. Prediger, G.F. Passos, P. Pandolfo, F.S.
Duarte, J.L. Franco, A.L. Dafre, G. Di Giunta, C.P. Figueiredo,
R.N. Takahashi, M.M. Campos, and J.B. Calixto, Connecting TNF-{alpha}
Signaling Pathways to iNOS Expression in a Mouse Model of Alzheimer's
Disease: Relevance for the Behavioral and Synaptic Deficits Induced
by Amyloid {beta} Protein. J Neurosci, 2007. 27(20):
p. 5394-5404.
27. Meme, W., C.F. Calvo, N. Froger, P. Ezan, E. Amigou, A. Koulakoff,
and C. Giaume, Proinflammatory cytokines released from microglia
inhibit gap junctions in astrocytes: potentiation by beta-amyloid.
Faseb J, 2006. 20(3): p. 494-6.
28. Mrak, R.E. and W.S. Griffin, Glia and their cytokines in
progression of neurodegeneration. Neurobiol Aging, 2005. 26(3):
p. 349-54.
29. Ralay Ranaivo, H., J.M. Craft, W. Hu, L. Guo, L.K. Wing, L.J.
Van Eldik, and D.M. Watterson, Glia as a therapeutic target:
selective suppression of human amyloid-beta-induced upregulation
of brain proinflammatory cytokine production attenuates neurodegeneration.
J Neurosci, 2006. 26(2): p. 662-70.
30. Takeuchi, H., S. Jin, J. Wang, G. Zhang, J. Kawanokuchi, R.
Kuno, Y. Sonobe, T. Mizuno, and A. Suzumura, Tumor necrosis
factor-alpha induces neurotoxicity via glutamate release from
hemichannels of activated microglia in an autocrine manner.
J Biol Chem, 2006. 281(30): p. 21362-8.
31. Tan, Z.S., A.S. Beiser, R.S. Vasan, and e. al., Inflammatory
markers and the risk of Alzheimer disease: The Framingham Study.
Neurology, 2007. 68(19): p. 1902-1908.
32. Zou, J.Y. and F.T. Crews, TNF alpha potentiates glutamate
neurotoxicity by inhibiting glutamate uptake in organotypic brain
slice cultures: neuroprotection by NF kappa B inhibition.
Brain Res, 2005. 1034(1-2): p. 11-24.
33. Zuliani, G., M. Ranzini, G. Guerra, L. Rossi, M.R. Munari,
A. Zurlo, S. Volpato, A.R. Atti, A. Ble, and R. Fellin, Plasma
cytokines profile in older subjects with late onset Alzheimer's
disease or vascular dementia. J Psychiatr Res, 2006.
34. Cohen, S.P., N. Bogduk, A.
Dragovich, C.C. Buckenmaier, 3rd, S. Griffith, C. Kurihara, J.
Raymond, P.J. Richter, N. Williams, and T.L. Yaksh, Randomized,
double-blind, placebo-controlled, dose-response, and preclinical
safety study of transforaminal epidural etanercept for the treatment
of sciatica. Anesthesiology, 2009. 110(5): p. 1116-26.
35. Kato, K., S. Kikuchi, V.I. Shubayev, and R.R. Myers, Distribution
and tumor necrosis factor-alpha isoform binding specificity of
locally administered etanercept into injured and uninjured rat
sciatic nerve. Neuroscience, 2009. 160(2): p. 492-500.
The following publications in 2007-8 have
cited scientific publications of Edward Tobinick MD, Director
of the INR®,
including the most recent publication:
Scientific
Articles:
1. Griffin WS. Perispinal etanercept: Potential as an Alzheimer
therapeutic. J Neuroinflammation. 2008 Jan 10;5(1):3. [download free full-text PDF].
2. Misra, Ambikanandan; Jogani, Viral; Jinturkar, Kaustubh; Vyas,
Tushar. Recent Patents Review on Intranasal Administration
for CNS Drug Delivery. Recent Patents on Drug Delivery &
Formulation, Volume 2, Number 1, January 2008 , pp. 25-40(16).
3. Zanella, John M. MS; Burright, Eric N. PhD; Hildebrand, Keith
DVM, PhD; Hobot, Chris BS; Cox, Mark BS; Christoferson, Laura
BS; McKay, William F. MS. Effect of Etanercept, a Tumor Necrosis
Factor-Alpha Inhibitor, on Neuropathic Pain in the Rat Chronic
Constriction Injury Model. Spine 33(3):227-234, February 1,
2008.
4. Sonya Vasto, Giuseppina Candore, Giovanni Duro, Domenico Lio,
Maria Paola Grimaldi, Calogero Caruso. Alzheimer's disease
and genetics of inflammation: a pharmacogenomic vision. Pharmacogenomics
December 2007, Vol. 8, No. 12, Pages 1735-1745.
5. Tweedie D, Sambamurti K, Greig NH. Drug Design & Development
Section, Laboratory of Neurosciences, Intramural Research Program,
National Institute on Aging, National Institutes of Health, Baltimore,
MD 21224, US. TNF-alpha Inhibition as a Treatment Strategy
for Neurodegenerative Disorders: New Drug Candidates and Targets.
Curr Alzheimer Res. 2007 Sep;4(4):375-8.
6. Van Eldik, L. J. Thompson, W. L. Ranaivo, H. R. Behanna, H.
A. Watterson, D. M. Glia Proinflammatory Cytokine Upregulation
as a Therapeutic Target for Neurodegenerative Diseases: Function-Based
and Target-Based Discovery Approaches, International Review
of Neurobiology 2007, 82:278-297.
7. Uceyler N, Sommer C. Cytokine-induced Pain: Basic Science
and Clinical Implications. Reviews in Analgesia 2007;9(2):87-103.
8. Tubbs RS, Hansasuta A, Loukas M, Louis RG, Jr., Shoja MM, Salter
EG, et al. The basilar venous plexus. Clin Anat 2007.
9. Saxena AK, Kumar S. Management strategies for pain in breast
carcinoma patients: current opinions and future perspectives.
Pain Pract 2007;7(2):163-77.
10. Owlia MB, Salimzadeh A, Alishiri G, Haghighi A. Comparison
of two doses of corticosteroid in epidural steroid injection for
lumbar radicular pain. Singapore Med J 2007;48(3):241-5.
11. Munoz L, Ralay Ranaivo H, Roy SM, Hu W, Craft JM, McNamara
LK, et al. A novel p38alpha MAPK inhibitor suppresses brain
proinflammatory cytokine up-regulation and attenuates synaptic
dysfunction and behavioral deficits in an Alzheimer's disease
mouse model. J Neuroinflammation 2007;4(1):21.
12. Hu W, Ranaivo HR, Roy SM, Behanna HA, Wing LK, Munoz L, et
al. Development of a novel therapeutic suppressor of brain
proinflammatory cytokine up-regulation that attenuates synaptic
dysfunction and behavioral deficits. Bioorg Med Chem Lett
2007;17(2):414-8.
13. Le Maitre CL, Hoyland JA, Freemont AJ. Catabolic cytokine
expression in degenerate and herniated human intervertebral discs:
IL-1beta and TNFalpha expression profile. Arthritis Res Ther.
2007 Aug 9;9(4):R77.
14. Kenneth M. Kulmatycki1, Fakhreddin Jamali. Drug Disease
Interactions: Role of Inflammatory Mediators in Pain and Variability
in Analgesic Drug Response. J Pharm Pharm Sci, 10 (4): 554-566,
2007.
15. Schäfers, Maria; Sommer, Claudia. Anticytokine
therapy in neuropathic pain management. Expert Review of Neurotherapeutics,
Volume 7, Number 11, November 2007 , pp. 1613-1627(15).
16. van Marum, R.J., Current
and future therapy in Alzheimer's disease. Fundam Clin Pharmacol,
2008. 22(3): p. 265-74.
17. Schwab, C. and P.L. McGeer, Inflammatory aspects of Alzheimer
disease and other neurodegenerative disorders. J Alzheimers
Dis, 2008. 13(4): p. 359-69.
18. Maczurek, A., K. Shanmugam, and G. Munch, Inflammation
and the redox-sensitive AGE-RAGE pathway as a therapeutic target
in Alzheimer's disease. Ann N Y Acad Sci, 2008. 1126:
p. 147-51.
19. Berbaum, K., K. Shanmugam, G. Stuchbury, F. Wiede, H. Korner,
and G. Munch, Induction of novel cytokines and chemokines by
advanced glycation endproducts determined with a cytometric bead
array. Cytokine, 2008. 41(3): p. 198-203.
Hardcover/
Bound Texts:
1. Neuroinflammation in Neuronal Death and Repair, Volume 82 (International
Review of Neurobiology.) G. Bagetta, editor (Hardcover - Jul 16,
2007) Amsterdam ; Boston : Elsevier Academic Press ©2007.
ISBN: 9780123739896 0123739896.
2. Interactions Between Neurons and Glia in Aging and Disease
by Joao Malva, Ana Cristina Rego, Rodrigo Cunha, and Catarina
Oliveira (Eds.) (Hardcover - Aug 22, 2007). 2007, Approx. 535
p., Hardcover ISBN: 978-0-387-70829-4 New York ; London : Springer,
2007.
3. Cytokines in the Genesis and Treatment of Cancer (Cancer Drug
Discovery and Development) by Michael A. Caligiuri and Michael
T. Lotze (Hardcover - April 20, 2007) Totowa, N.J. : Humana Press
©2007. ISBN: 9780896038202 0896038203 9781597454551 1597454559.
4. Chapter 10: Anti-TNF-alpha antibody and cancer cachexia, The
ASCRS Textbook of Colon and Rectal Surgery by J.M. Church, J.
Garcia-Aguilar, P.L. Roberts, and T.J. Saclarides; New York :
Springer ©2007. ISBN: 9780387248462 0387248463.
5. Spinal Reconstruction: Clinical Examples of Applied Basic Science,
Biomechanics and Engineering by Kai-Uwe Lewandrowski, Michael
J. Yaszemski, Iain Kalfas, and Paul Park (Hardcover - Feb 12,
2007) New York : Informa Healthcare ©2007. ISBN: 9780849398155
0849398150.
6. Olesen J, Jensen T. From Basic Pain Mechanisms to Headache.
Oxford University Press 2007.
7. Neuroimmunology: The Immune System and Alzheimers, in the 2007
Progress Report on Brain Research, Dana Alliance for Brain Initiatives,
Dana Press, New York ©2007.