CONTEXT: Current pharmacologic treatments for Alzheimer's disease (AD) do not prevent long-term clinical deterioration. Tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine, has been implicated in the pathogenesis of AD. OBJECTIVE: To investigate the use of a biologic TNF-alpha inhibitor, etanercept was given by perispinal extrathecal administration for the treatment of AD. METHODS: This was a prospective, single-center, open-label, pilot (proof-of-concept) study, in which 15 patients with mild-to-severe AD were treated for 6 months. We administered etanercept, 25-50 mg, once weekly by perispinal administration. Main outcome measures included the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), and the Severe Impairment Battery (SIB). RESULTS: The average age of our patient population was 76.7. The mean baseline MMSE was 18.2 (n = 15); the mean baseline ADAS-Cog was 20.8 (n = 11); and the mean baseline SIB was 62.5 (n = 5). There was significant improvement with treatment, as measured by all of the primary efficacy variables, through 6 months: MMSE increased by 2.13 -/+ 2.23, ADAS-Cog improved (decreased) by 5.48 -/+ 5.08, and SIB increased by 16.6 -/+ 14.52. CONCLUSION: An increasing amount of basic science and clinical evidence implicates inflammatory processes and resulting glial activation in the pathogenesis of AD. This small, open-label pilot study suggests that inhibition of the inflammatory cytokine TNF-alpha may hold promise as a potential approach to AD treatment. Further study in randomized, placebo-controlled clinical trials is merited.
CONTEXT: Current pharmacologic treatments for Alzheimer's disease (AD) do not prevent long-term clinical deterioration. Tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine, has been implicated in the pathogenesis of AD. OBJECTIVE: To investigate the use of a biologic TNF-alpha inhibitor, etanercept was given by perispinal extrathecal administration for the treatment of AD. METHODS: This was a prospective, single-center, open-label, pilot (proof-of-concept) study, in which 15 patients with mild-to-severe AD were treated for 6 months. We administered etanercept, 25-50 mg, once weekly by perispinal administration. Main outcome measures included the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), and the Severe Impairment Battery (SIB). RESULTS: The average age of our patient population was 76.7. The mean baseline MMSE was 18.2 (n = 15); the mean baseline ADAS-Cog was 20.8 (n = 11); and the mean baseline SIB was 62.5 (n = 5). There was significant improvement with treatment, as measured by all of the primary efficacy variables, through 6 months: MMSE increased by 2.13 -/+ 2.23, ADAS-Cog improved (decreased) by 5.48 -/+ 5.08, and SIB increased by 16.6 -/+ 14.52. CONCLUSION: An increasing amount of basic science and clinical evidence implicates inflammatory processes and resulting glial activation in the pathogenesis of AD. This small, open-label pilot study suggests that inhibition of the inflammatory cytokine TNF-alpha may hold promise as a potential approach to AD treatment. Further study in randomized, placebo-controlled clinical trials is merited.
Authors: Sara L Montgomery; Michael A Mastrangelo; Diala Habib; Wade C Narrow; Sara A Knowlden; Terry W Wright; William J Bowers Journal: Am J Pathol Date: 2011-08-09 Impact factor: 4.307
Authors: Wenhui Hu; Hantamalala Ralay Ranaivo; Saktimayee M Roy; Heather A Behanna; Laura K Wing; Lenka Munoz; Ling Guo; Linda J Van Eldik; D Martin Watterson Journal: Bioorg Med Chem Lett Date: 2006-10-17 Impact factor: 2.823
Authors: Robert M Starke; Daniel M S Raper; Dale Ding; Nohra Chalouhi; Gary K Owens; David M Hasan; Ricky Medel; Aaron S Dumont Journal: Transl Stroke Res Date: 2013-09-20 Impact factor: 6.829
Authors: Meredith Hay; Robin Polt; Michael L Heien; Todd W Vanderah; Tally M Largent-Milnes; Kathleen Rodgers; Torsten Falk; Mitchell J Bartlett; Kristian P Doyle; John P Konhilas Journal: J Pharmacol Exp Ther Date: 2019-02-01 Impact factor: 4.030