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MedGenMed. 2006 Apr 26;8(2):25.

TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study.

Author information

  • 1University of California, Los Angeles, California, USA. etmd@ucla.edu

Abstract

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.

Comment in

PMID:
16926764
[PubMed - indexed for MEDLINE]
PMCID:
PMC1785182
Free PMC Article

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