Primary progressive aphasia (PPA) is an uncommon form of progressive
dementia for which there exists no established treatment. The underlying pathology may be that of either
frontotemporal dementia or
Alzheimer's disease. Increasing evidence suggests that excess
tumor necrosis factor (TNF) may play a central role in
Alzheimer's disease. Additionally, excess TNF has been documented in patients with
frontotemporal dementia. Excess TNF may therefore represent a therapeutic target in PPA.
Etanercept, an anti-TNF fusion
protein, binds to TNF, thereby reducing its
biologic effect. Emerging evidence suggests that perispinal administration of
etanercept may have therapeutic efficacy for
Alzheimer's disease. This evidence, in combination, supports a rationale for the use of perispinal
etanercept for the treatment of PPA. This report documents rapid improvement in verbal abilities, beginning within 20 minutes of perispinal
etanercept, in a patient with severe PPA. With repeated weekly dosing, sustained improvement at 1 month is documented, with a more than 10-point improvement in the patient's abilities to perform
activities of daily living as measured by a standardized instrument, the
Alzheimer's Disease Cooperative Study-
Activities of Daily Living inventory. Rapid clinical improvement in PPA following perispinal
etanercept administration may be related to TNF's role as a gliotransmitter and modulator of synaptic communication in the brain. These results may provide insight into the basic pathophysiologic mechanisms underlying PPA and related forms of
dementia and suggest the existence of novel, rapidly reversible, TNF-mediated pathophysiologic mechanisms in both PPA and
Alzheimer's disease. Further study of this therapeutic method is indicated.