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COMPOSITIONS AND METHODS FOR AMELIORATING CNS INFLAMMATION, PSYCHOSIS, DELIRIUM, PTSD or PTSS

  • US 20100297070A1
  • Filed: 10/18/2008
  • Published: 11/25/2010
  • Est. Priority Date: 10/19/2007
  • Status: Active Grant
First Claim
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1. A method for ameliorating, reversing, treating or preventing an inflammation or a central nervous system (CNS) inflammation, a schizophrenia, a psychosis, a delirium, a post-operative delirium, a drug-induced psychosis, a frailty syndrome (FS), psychotic features associated with frailty syndrome (FS), aging, depression, dementias;

  • trauma, traumatic war neurosis, post traumatic stress disorder (PTSD), post-traumatic stress syndrome (PTSS), Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig'"'"'s Disease), and/or Multiple Sclerosis (MS), inflammation from CNS infections, and/or cognitive, learning or memory impairments resulting therefrom, in an individual comprising;

    (a) (i) providing a composition that(1) inhibits or decreases the in vivo activity of NFkB, interleukin-6 (IL-6), interleukin-6 receptor (IL-6-R) or a member of the NADPH oxidase enzyme family (Nox), and/or inhibits or decreases superoxide and/or hydrogen peroxide production by a member of the NADPH oxidase enzyme family, or(2) acts as a superoxide dismutase mimetic to decrease superoxide and/or hydrogen peroxide; and

    (ii) administering an effective amount of the composition of (a) to the individual in need thereof;

    (b) the method of (a), wherein the individual is a human;

    (c) the method of (a) or (b), wherein the composition comprises a pharmaceutical formulation;

    (d) the method of (c), wherein the pharmaceutical formulation is formulated for delivery to the brain or a neural cell, or for passing through the blood brain barrier (BBB);

    (e) the method of (d), wherein the pharmaceutical formulation is formulated for delivery to a parvalbumin-positive GABA-ergic interneuron;

    (f) the method of any of (a) to (c), wherein the pharmaceutical formulation comprises a therapeutic monoclonal antibody specific for and inhibitory to the activity of NFkB. an IL-6 or IL-6-R and/or an NADPH oxidase enzyme;

    (g) the method of (f), wherein the therapeutic monoclonal antibody is a humanized or a human antibody;

    (h) the method of (f) or (g), wherein the therapeutic monoclonal antibody against the IL-6-R is tocilizumab, or ACTEMRA™

    , or the therapeutic monoclonal antibody is against IL-6, or is CNTO-328, a human-mouse chimeric monoclonal antibody (Mab) to IL-6;

    (i) the method of (a) or (b), wherein the composition comprises a small molecule;

    (j) the method of (i), wherein the small molecule comprises an o-methoxycatechol, an apocynin, a diapocynin, 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), 4-hydroxy-3′

    -methoxy-acetophenon, N-Vanillylnonanamide, staurosporine or related compounds;

    (k) the method of (a) or (b), wherein the composition comprises an inhibitory nucleic acid molecule to NFkB, IL-6 or NADPH oxidase;

    (l) the method of (k), wherein the inhibitory nucleic acid molecule comprises an RNAi molecule, a double-stranded RNA (dsRNA) molecule, an sRNA, a miRNA (microRNA) and/or a short hairpin RNA (shRNA) molecule, or a ribozyme, or a fragment of an NADPH oxidase-encoding nucleic acid;

    (m) the method of any of (a) to (l), wherein the member of the NADPH oxidase enzyme family (Nox) is a Nox1, Nox2, Nox3, Nox4 or Nox5 enzyme;

    (n) the method of any of (a) to (l), wherein the infection is a viral, bacterial, yeast and/or fungal infection, or a Haemophilus, Cryptococcus, Filobasidiella, Neisseria, Rickettsia or Borrelia infection;

    (o) the method of any of (a) to (n), wherein the composition that inhibits or decreases the in vivo activity of NFkB, interleukin-6 (IL-6) or IL-6R is an antibody against NFkB IL-6 or IL-6-R, respectively;

    (p) the method of (o), wherein the composition that inhibits or decreases the in vivo activity of interleukin-6 (IL-6) is interleukin-10 (IL-10);

    (q) the method of (p), wherein the composition that inhibits or decreases the in vivo activity of interleukin-6 (IL-6) is ilodecakin or TENOVIL™

    ;

    or(r) the method of any of (a) to (n), wherein superoxide dismutase mimetic that decreases superoxide and/or hydrogen peroxide comprises a C60 fullerene, C3 (tris malonic acid C60) or a malonic acid derivative.

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