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


CONCLUSIONS
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.
Tobinick
Edward
E
University of California, Los Angeles, California, USA. etmd@ucla.edu
Gross
Hyman
H
Weinberger
Alan
A
Cohen
Hart
H
D000368:Aged; D000369:Aged, 80 and over; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D014409:Tumor Necrosis Factor-alpha