About the INR

The INR has made a stunning discovery: that the neurological status of patients following stroke or brain injury, even years after the acute event, may rapidly improve following the use of an anti-TNF therapeutic.

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These published results, and more than five years of clinical experience, suggest that excess TNF plays an important role in post-stroke chronic disability and establish the promise that the INR’s patented anti-TNF treatment presents for stroke recovery and stroke rehabilitation. Results can vary, and more than one dose may be necessary for optimal benefit, please see the Terms of Use, but these results represent a new breakthrough in the understanding of the neurological basis of chronic brain dysfunction following stroke.

Consultation following Stroke or Brain Injury at the INR

Patients who have experienced stroke or brain injury often have weakness or decreased sensation in one half of the body, cognitive or speech difficulties, or other neurological problems that can last for years. Consultation with an INR medical provider after hospital discharge is encouraged, even if the stroke or brain injury has occurred years before. Please call the INR in Florida at +1 (561) 353-9707 for further information.

Appointments at the INR

Consultation and treatment are by appointment only.  Phone or in-office consultations can be scheduled by calling the INR in Florida at +1 (561) 353-9707 for further information.

Referrals to the INR

The INR welcomes referrals from neurologists, geriatricians, internists, family physicians, other health care providers, or family members of patients with selected neuroinflammatory disorders. Please note: INR medical providers utilize etanercept for a limited number of off-label indications. INR medical providers do not use etanercept for treating Parkinson’s disease, brain tumor, or carpal tunnel syndrome. Individual treatment recommendations are only made following a phone or in-office consultation, including history, physical examination, and review of imaging studies.

The INR welcomes telephone inquiries from physicians and family members. In particular, the INR encourages telephone inquiry and discussion with an INR medical provider for those patients referred from locations at a geographic distance from Boca Raton, Florida, prior to appointment scheduling. This is recommended especially for those patients who will be flying across country or from overseas for treatment at the INR, due to the special nature of the services provided at the INR, and the unique experience which the INR has performing anti-TNF treatment for neurological disorders.

Relevant Scientific Publications

**Indicates articles of particular interest

**1.        Perispinal etanercept: a new therapeutic paradigm in neurology. Edward Tobinick MD. Expert Review of Neurotherapeutics. 2010 Jun;10(6):985-1002.

**2.        Perispinal etanercept for neuroinflammatory disorders. Edward Tobinick MD. Drug Discovery Today. 2009 Feb;14(3-4):168-77.

3.         Roh, M., et al., Etanercept, a widely used inhibitor of tumor necrosis factor-alpha (TNF-alpha), prevents retinal ganglion cell loss in a rat model of glaucoma. PLoS One, 2012. 7(7): p. e40065.

**4.         Santello, M. and A. Volterra, TNFalpha in synaptic function: switching gears. Trends Neurosci, 2012. 35(10): p. 638-47.

5.         Smith, C., et al., The neuroinflammatory response in humans after traumatic brain injury. Neuropathol Appl Neurobiol, 2012.

**6.         Tobinick, E., Deciphering the physiology underlying the rapid clinical effects of perispinal etanercept in Alzheimer’s disease. Curr Alzheimer Res, 2012. 9(1): p. 99-109.

**7.         Tobinick, E., et al., Selective TNF Inhibition for Chronic Stroke and Traumatic Brain Injury : An Observational Study Involving 629 Consecutive Patients Treated with Perispinal Etanercept. CNS Drugs, 2012. 26(12): p. 1051-70.

**8.         Blaylock, R.L., Immunology primer for neurosurgeons and neurologists part 2: Innate brain immunity. Surg Neurol Int, 2013. 4: p. 118.

**9.         Cheong, C.U., et al., Etanercept attenuates traumatic brain injury in rats by reducing brain TNF- alpha contents and by stimulating newly formed neurogenesis. Mediators Inflamm, 2013. 2013: p. 620837.

**10.       Chio, C.C., et al., Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-alpha. BMC Neurosci, 2013. 14(1): p. 33.

11.       Efrati, S., et al., Hyperbaric oxygen induces late neuroplasticity in post stroke patients–randomized, prospective trial. PLoS One, 2013. 8(1): p. e53716.

12.       Iwatsuki, K., et al., Targeting anti-inflammatory treatment can ameliorate injury-induced neuropathic pain. PLoS One, 2013. 8(2): p. e57721.

**13.       Johnson, V.E., et al., Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain, 2013. 136(Pt 1): p. 28-42.

**14.       King, M.D., C.H. Alleyne, Jr., and K.M. Dhandapani, TNF-alpha receptor antagonist, R-7050, improves neurological outcomes following intracerebral hemorrhage in mice. Neurosci Lett, 2013. 542: p. 92-6.

15.       Kumar, A., et al., Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states. Neurobiol Aging, 2013. 34(5): p. 1397-411.

**16.       Lei, B., et al., Tumor necrosis factor alpha antagonism improves neurological recovery in murine intracerebral hemorrhage. J Neuroinflammation, 2013. 10(1): p. 103.

17.       Petzold, A. and A. Girbes, Pain management in neurocritical care. Neurocrit Care, 2013. 19(2): p. 232-56.

18.       Starke, R.M., et al., Tumor Necrosis Factor-alpha Modulates Cerebral Aneurysm Formation and Rupture. Translational Stroke Research, 2013. 10.1007/s12975-013-0287-9.

**19.       Waters, R.J., et al., Cytokine gene polymorphisms and outcome after traumatic brain injury. J Neurotrauma, 2013. 30(20): p. 1710-6.

**20.       Works, M.G., J.B. Koenig, and R.M. Sapolsky, Soluble TNF receptor 1-secreting ex vivo-derived dendritic cells reduce injury after stroke. J Cereb Blood Flow Metab, 2013.

INR Scientific Background

The INR’s scientific findings have been published in multiple, peer-reviewed medical journals, including Expert Review of Neurotherapeutics, CNS Drugs, BMC Neurology, Current Alzheimer ResearchClinical TherapeuticsDrug 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. There have been hundreds of scientific citations to INR publications, including in Nature Clinical Practice Neurology and F1000 Biology.

Edward Tobinick, MD, founder of the INR, has presented his scientific findings regarding the effects of etanercept for neurological disorders 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 Diseasein 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, the World Pharmaceutical Congress in Philadelphia and the 5th Modern Drug Discovery Conference in San Diego. Dr. Tobinick has performed collaborative research with scientists from Stanford University School of Medicine and additional academic centers.

2010-2012 Scientific Publications citing INR publications

The following are selected publications that have cited scientific publications of Edward Tobinick MD, Founder of the INR®, in 2012:

1. Belarbi, K., et al., TNF-alpha protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation. J Neuroinflammation, 2012. 9: p. 23.

2. Bomfim, T.R., et al., An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease- associated Abeta oligomers. J Clin Invest, 2012. 122(4): p. 1339-53.

3. Butchart, J. and C. Holmes, Systemic and central immunity in Alzheimer’s disease: therapeutic implications. CNS Neurosci Ther, 2012. 18(1): p. 64-76.

4. Cereda, C., et al., The Role of TNF-alpha in ALS: New Hypostheses for Future Therapeutic Approaches, in Amyotrophic Lateral Sclerosis, M.H. Maurer, Editor. 2012, InTech. p. 413-436.

5. Clark, I., et al., Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer’s disease links numerous treatment rationales. Pharmacol Rev, 2012. 64(4): p. 1004-26.

6. Dhawan, G. and C.K. Combs, Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer’s disease. J Neuroinflammation, 2012. 9: p. 117.

7. Drent, M., E.E. Lower, and J. De Vries, Sarcoidosis-associated fatigue. Eur Respir J, 2012. 40(1): p. 255-63.

8. Ferraccioli, G., et al., Rheumatoid Arthritis and Alzheimer Disease: Possible Cellular and Molecular Links. Gerontology and Geriatric, 2012. 1(1).

9. Gabbita, S.P., et al., Early intervention with a small molecule inhibitor for tumor necrosis factor-alpha prevents cognitive deficits in a triple transgenic mouse model of Alzheimer’s disease. J Neuroinflammation, 2012. 9: p. 99.

10. Gruber, H.E., et al., Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus. Mol Pain, 2012. 8(1): p. 63.

11. Hojlund, J., et al., Effect of head rotation on cerebral blood velocity in the prone position. Anesthesiol Res Pract, 2012. 2012: p. 647258.

12. Ingles-Esteve, J., et al., Inhibition of specific NF-kappaB activity contributes to the tumor suppressor function of 14-3-3sigma in breast cancer. PLoS One, 2012. 7(5): p. e38347.

13. Jiang, T., J.T. Yu, and L. Tan, Novel disease-modifying therapies for Alzheimer’s disease. J Alzheimers Dis, 2012. 31(3): p. 475-92.

14. Krishnadas, R. and J. Cavanagh, Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry, 2012. 83(5): p. 495-502.

15. Landoni, V.I., et al., Shiga toxin 1 induces on lipopolysaccharide-treated astrocytes the release of tumor necrosis factor-alpha that alter brain-like endothelium integrity. PLoS Pathog, 2012. 8(3): p. e1002632.

16. Lauterbach, E.C., Psychotropic drug effects on gene transcriptomics relevant to Alzheimer disease. Alzheimer Dis Assoc Disord, 2012. 26(1): p. 1-7.

17. Lima, A. and F. Antunes, Intervention of Physical Medicine and Rehabilitation in Failed Back Surgery Syndrome. Journal of Regional Anaesthesia and Pain Management, 2012. 68: p. 29-30.

18. Maccioni, R.B., et al., In Search of Therapeutic Solutions for Alzheimer’s Disease, in When Things Go Wrong–Diseases and Disorders of the Human Brain, T. Mantamadiotis, Editor. 2012, InTech. p. 125-.

19. Matias-Guiu, J.A. and R. Garcia-Ramos, Primary progressive aphasia: from syndrome to disease. Neurologia, 2012.

20. Montgomery, S.L. and W.J. Bowers, Tumor Necrosis Factor-alpha and the Roles it Plays in Homeostatic and Degenerative Processes Within the Central Nervous System. Journal of Neuroimmune Pharmacology, 2012. 7(1): p. 42-59.

21. Ooi, L., et al., New drugs under development for Alzheimer’s disease, in Advances in Alzheimer’s Disease Management, S. Gauthier and P. Rosa-Neto, Editors. 2012. p. 58-67.

22. Ramesh, V., et al., Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-alpha pathway. J Neuroinflammation, 2012. 9.

23. Santello, M. and A. Volterra, TNF-alpha in synaptic function: switching gears. Trends Neurosci, 2012. 35(10): p. 638-47.

24. Singh, P.L., et al., Current therapeutic strategies for inflammation following traumatic spinal cord injury. Neural Regeneration Research, 2012. 7(23): p. 1812-1821.

25. Steele, M.L. and S.R. Robinson, Reactive astrocytes give neurons less support: implications for Alzheimer’s disease. Neurobiol Aging, 2012. 33(2): p. 423 e1-13.

26. Stringer, M.D., et al., The vertebral venous plexuses: the internal veins are muscular and external veins have valves. Clin Anat, 2012. 25(5): p. 609-18.

27. Tweedie, D., et al., Tumor necrosis factor-alpha synthesis inhibitor 3,6′-dithiothalidomide attenuates markers of inflammation, Alzheimer pathology and behavioral deficits in animal models of neuroinflammation and Alzheimer’s disease. J Neuroinflammation, 2012. 9: p. 106.

28. Wilcock, D.M., Neuroinflammation in the aging down syndrome brain; lessons from Alzheimer’s disease. Curr Gerontol Geriatr Res, 2012. 2012: p. 170276.

29. Woodward, M.C., Drug treatments in development for Alzheimer’s disease. Journal of Pharmacy Practice and Research, 2012. 42(1): p. 58-65.

30. Yoshiyama, Y., V.M. Lee, and J.Q. Trojanowski, Therapeutic strategies for tau mediated neurodegeneration. J Neurol Neurosurg Psychiatry, 2012.

The INR’s scientific publications have been cited and discussed in scientific publications from academic centers around the world, including the following publications in 2010 and 2011:

  • Aderinwale, O.G., H.W. Ernst, and S.A. Mousa, Current therapies and new strategies for the management of Alzheimer’s disease. Am J Alzheimers Dis Other Demen, 2010. 25: (5): p. 414-24.
  • Bassi, E. and C. De Filippi, Beneficial neurological effects observed in a patient with psoriasis treated with etanercept. Am J Clin Dermatol, 2010. 11 Suppl 1: p. 44-5.
  • Boettger, M.K., et al., Spinal tumor necrosis factor alpha neutralization reduces peripheral inflammation and hyperalgesia and suppresses autonomic responses in experimental arthritis: a role for spinal tumor necrosis factor alpha during induction and maintenance of peripheral inflammation. Arthritis Rheum, 2010. 62(5): p. 1308-18.
  • Buchhave, P., et al., Soluble TNF receptors are associated with Abeta metabolism and conversion to dementia in subjects with mild cognitive impairment. Neurobiol Aging, 2010. 31(11): p. 1877-84.
  • Candore, G., et al., Inflammation, cytokines, immune response, apolipoprotein E, cholesterol, and oxidative stress in Alzheimer disease: therapeutic implications. Rejuvenation Res, 2010. 13(2-3): p. 301-13.
  • Chavant, F., et al., Imipramine, in part through tumor necrosis factor alpha inhibition, prevents cognitive decline and beta-amyloid accumulation in a mouse model of Alzheimer’s disease. J Pharmacol Exp Ther, 2010. 332(2): p. 505-14.
  • Chez, M.G. and N. Guido-Estrada, Immune therapy in autism: historical experience and future directions with immunomodulatory therapy. Neurotherapeutics, 2010. 7(3): p. 293-301.
  • Clark, I.A., L.M. Alleva, and B. Vissel, The roles of TNF in brain dysfunction and disease. Pharmacol Ther, 2010.128(3): p. 519-48.
  • Colton, C.A. and D.M. Wilcock, Assessing activation states in microglia. CNS Neurol Disord Drug Targets, 2010.9(2): p. 174-91.
  • Dumont, T.M., D.W. Stockwell, and M.A. Horgan, Venous air embolism: an unusual complication of atlantoaxial arthrodesis: case report. Spine (Phila Pa 1976), 2010. 35(22): p. E1238-40.
  • Duro, D., et al., Validation studies of the Portuguese experimental version of the Montreal Cognitive Assessment (MoCA): confirmatory factor analysis. J Neurol, 2010. 257(5): p. 728-34.
  • Elfferich, M.D., et al., Everyday cognitive failure in sarcoidosis: the prevalence and the effect of anti-TNF-alpha treatment. Respiration, 2010. 80(3): p. 212-9.
  • Esposito, E. and S. Cuzzocrea, Anti-TNF therapy in the injured spinal cord. Trends Pharmacol Sci. 2011 Feb;32(2):107-15.
  • Frankola KA, Greig NH, Luo W, Tweedie D. Targeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative Diseases. CNS Neurol Disord Drug Targets. 2011 Feb 2. [Epub ahead of print] PMID: 21288189
  • Furst, D.E., et al., Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009. Ann Rheum Dis, 2010. 69 Suppl 1: p. i2-29.
  • Galimberti D, Scarpini E. Alzheimer’s Disease: From Pathogenesis to Disease-Modifying Approaches. CNS & Neurological Disorders – Drug Targets March 2011. 10(2):163-174.
  • Geis, C., et al., Evoked pain behavior and spinal glia activation is dependent on tumor necrosis factor receptor 1 and 2 in a mouse model of bone cancer pain. Neuroscience, 2010. 169(1): p. 463-74.
  • Gu, X., et al., Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-alpha expression in a mouse model. Mol Pain, 2010. 6: p. 64.
  • He, M.X., et al., Association between interleukin-6 gene promoter -572C/G polymorphism and the risk of sporadic Alzheimer’s disease. Neurol Sci, 2010. 31(2): p. 165-8.
  • Huang, H., et al., TNF{alpha} is required for late BRB breakdown in diabetic retinopathy and its inhibition prevents leukostasis and protects vessels and neurons from apoptosis. Invest Ophthalmol Vis Sci, 2011 Jan 6.
  • Landoni, V.I., et al., Shiga toxin 1-induced inflammatory response in lipopolysaccharide-sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha. Infect Immun, 2010. 78(3): p. 1193-201.
  • Lanni, C., et al., The expanding universe of neurotrophic factors: therapeutic potential in aging and age-associated disorders. Curr Pharm Des, 2010. 16(6): p. 698-717.
  • Liu, Z.P., et al., Identifying dysfunctional crosstalk of pathways in various regions of Alzheimer’s disease brains. BMC Syst Biol, 2010. 4 Suppl 2: p. S11.
  • McIntyre, R.S., et al., Brain volume abnormalities and neurocognitive deficits in diabetes mellitus: points of pathophysiological commonality with mood disorders? Adv Ther, 2010. 27(2): p. 63-80.
  • McNaull, B.B., et al., Inflammation and anti-inflammatory strategies for Alzheimer’s disease–a mini-review. Gerontology, 2010. 56(1): p. 3-14.
  • Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Bienfait K, Dicke A, Kusnekov A. The role of inflammatory cytokines in cognition and other non-motor symptoms of Parkinson’s disease. Psychosomatics. 2010 Nov;51(6):474-9.
  • Merino, A., et al., Drug profiling: knowing where it hits. Drug Discov Today, 2010. 15(17-18): p. 749-56.
  • Money, T.T., et al., Treating schizophrenia: novel targets for the cholinergic system. CNS Neurol Disord Drug Targets, 2010. 9(2): p. 241-56.
  • Munoz, L. and A.J. Ammit, Targeting p38 MAPK pathway for the treatment of Alzheimer’s disease. Neuropharmacology, 2010. 58(3): p. 561-8.
  • Nicolae, C. and B.R. Olsen, Unexpected matrix diseases and novel therapeutic strategies. Cell Tissue Res, 2010.339(1): p. 155-65.
  • Oldreive, C.E. and G.H. Doherty, Effects of tumour necrosis factor-alpha on developing cerebellar granule and Purkinje neurons in vitro. J Mol Neurosci, 2010. 42(1): p. 44-52.
  • Pan, S.Y., et al., New perspectives on innovative drug discovery: an overview. J Pharm Pharm Sci, 2010. 13(3): p. 450-71.
  • Potter, P.E., Investigational medications for treatment of patients with Alzheimer disease. J Am Osteopath Assoc, 2010.110(9 Suppl 8): p. S27-36.
  • Ramanan, S., et al., Role of PPARs in Radiation-Induced Brain Injury. PPAR Res, 2010. 2010: p. 234975.
  • Seigers, R. and J.E. Fardell, Neurobiological basis of chemotherapy-induced cognitive impairment: a review of rodent research. Neurosci Biobehav Rev, 2011. 35(3): p. 729-41.
  • Simen AA, Bordner KA, Martin MP, et. al., Cognitive dysfunction with aging and the role of inflammation. Therapeutic Advances in Chronic Disease, 2011. Published online before print February 15, 2011, doi:10.1177/2040622311399145.
  • Sinclair, S.M., et al., Attenuation of Inflammatory Events in Human Intervertebral Disc Cells with a Tumor Necrosis Factor Antagonist. Spine (Phila Pa 1976), 2011 Jan 6.
  • Tamayo AC, Guajardo-Rosas J. Cervical epidural injections for radicular pain. Techniques in Regional Anesthesia and Pain Management. Volume 14, Issue 3, July 2010, Pages 106-112.
  • Vinukonda, G., et al., Neuroprotection in a rabbit model of intraventricular haemorrhage by cyclooxygenase-2, prostanoid receptor-1 or tumour necrosis factor-alpha inhibition. Brain, 2010. 133(Pt 8): p. 2264-80.
  • Wang, M.J., et al., Glycogen synthase kinase-3beta inactivation inhibits tumor necrosis factor-alpha production in microglia by modulating nuclear factor kappaB and MLK3/JNK signaling cascades. J Neuroinflammation, 2010. 7: p. 99.

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