On March 30, 2013, new data from the UCSF Memory and Aging Center published pointing to excess TNF as a potential therapeutic target for certain forms of dementia. In particular, elevated TNF levels were observed in the cohort of individuals examined with semantic variant PPA (primary progressive aphasia) (see Miller ZA, Rankin KP, Graff-Radford NR, Takada LT, Sturm VE, Cleveland CM, Criswell LA, Jaeger PA, Stan T, Heggeli KA, et al: TDP-43 frontotemporal lobar degeneration and autoimmune disease. J Neurol Neurosurg Psychiatry 2013).
We note that this UCSF study follows by more than four years the initial report of rapid clinical improvement in an individual with PPA following the off-label use of perispinal etanercept (Tobinick E: Perispinal etanercept produces rapid improvement in primary progressive aphasia: identification of a novel, rapidly reversible TNF-mediated pathophysiologic mechanism. Medscape J Med 2008, 10:135).
We were so pleased that Jan returned to visit us on March 11 from Kennett, Missouri with her husband. She is holding the story the Daily Dunklin Democrat had printed on February 17 about her rapid improvement after treatment. To read the whole story please click on the following link to the webpage of the Daily Dunklin Democrat (click here).
TNF-alpha receptor antagonist, R-7050, improves neurological outcomes following intracerebral hemorrhage in mice
Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, exhibits the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, treatment options for ICH are lacking due in part to a lack of feasible therapeutic targets. Inflammatory activation is associated with neurological deficits in pre-clinical ICH models and with patient deterioration after clinical ICH. In the present study, we tested the hypothesis that R-7050, a novel cell permeable triazoloquinoxaline inhibitor of the tumor necrosis factor receptor (TNFR) complex, attenuates neurovascular injury after ICH in mice. Up to 2 h post-injury administration of R-7050 significantly reduced blood–brain barrier opening and attenuated edema development at 24 h post-ICH. Neurological outcomes were also improved over the first 3 days after injury. In contrast, R-7050 did not reduce hematoma volume, suggesting the beneficial effects of TNFR inhibition were downstream of clot formation/resolution. These data suggest a potential clinical utility for TNFR antagonists as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.