Methods of treating or preventing alzheimer's disease and associated conditions

Abstract

The present invention describes a method of treating, preventing, reducing the likelihood of or alleviating a symptom of Alzheimer's disease and associated conditions by increasing OPN expression. The invention further provides for a method of improving cognitive function in a subject in need thereof.

What is claimed is: 
     
         1 . A method of treating, preventing or reducing the likelihood of Alzheimer's disease, alleviating a symptom of Alzheimer's disease, rescuing synaptic structure and/or cognitive function, enhancing the clearance of pathological amyloid-β forms or inhibiting the decline of neuronal structure and function in a subject in need thereof comprising:
 providing a composition that, when administered to the subject, results in increased levels of osteopontin (OPN) relative to a normal subject; and 
 administering an amount of the composition to the subject sufficient to increase said levels of OPN. 
 
     
     
         2 . The method of  claim 1 , wherein the composition comprises OPN expressing innate immune cells, recombinant OPN, OPN fragments, OPN derivatives, OPN mimetics, OPN analogues or a combination thereof. 
     
     
         3 . The method of  claim 1 , wherein the composition stimulates expression of OPN in innate immune cells. 
     
     
         4 . The method of  claim 3 , wherein the innate immune cells comprise monocytes, macrophages or combinations thereof. 
     
     
         5 . The method of  claim 4 , wherein the monocytes comprise bone marrow-derived monocytes, spleen-derived monocytes, CD115 positive monocytes (CD115 +  monocytes) or combinations thereof. 
     
     
         6 . The method of  claim 4 , wherein the monocytes are infiltrating monocytes and become OPN expressing macrophages in the brain. 
     
     
         7 . The method of  claim 3 , wherein the innate immune cells are phagocytic. 
     
     
         8 . The method of  claim 3 , wherein the composition comprises glatiramer acetate (GA). 
     
     
         9 . The method of  claim 3 , wherein the innate immune cells are stimulated ex vivo or in vivo. 
     
     
         10 . The method of  claim 3 , wherein innate immune cells expressing OPN are administered to the subject by adoptive cell transfer or bone marrow transplantation. 
     
     
         11 . The method of  claim 10 , wherein the innate immune cells over-express OPN. 
     
     
         12 . The method of  claim 1 , wherein the composition is administered by a method selected from the group consisting of direct delivery to the subject, viral vector delivery, a liposomal delivery system, or nanodrug delivery system. 
     
     
         13 . The method of  claim 1 , wherein the symptom of Alzheimer's disease is selected from the group consisting of memory loss, decline in non-memory aspects of cognition, impaired reasoning or judgment, behavior changes, carry out multistep tasks, hallucinations, delusions, paranoia and combinations thereof. 
     
     
         14 . The method of  claim 1 , wherein the administration of the composition results in an increase in MMP-9. 
     
     
         15 . The method of  claim 1 , wherein elevated OPN expression results in decreased levels of a misfolded protein in the subject. 
     
     
         16 . The method of  claim 15 , wherein the misfolded protein is amyloid beta (Aβ). 
     
     
         17 . The method of  claim 16 , wherein the Aβ is Aβ 40  and/or Aβ 42 . 
     
     
         18 . A method of improving cognitive function in a subject in need thereof, comprising:
 providing a composition that, when administered to the subject, results in increased levels of osteopontin (OPN) relative to a normal subject; and   administering an amount of the composition to the subject sufficient to increase said levels of OPN.   
     
     
         19 . The method of  claim 18 , wherein the composition comprises OPN expressing innate immune cells, recombinant OPN, OPN fragments, OPN derivatives, OPN mimetics, OPN analogues or a combination thereof. 
     
     
         20 . The method of  claim 18 , wherein the composition stimulates expression of OPN in innate immune cells. 
     
     
         21 . The method of  claim 20 , wherein the innate immune cells comprise monocytes, macrophages or combinations thereof. 
     
     
         22 . The method of  claim 21 , wherein the monocytes comprise bone marrow-derived monocytes, spleen-derived monocytes, CD115 positive monocytes (CD115 +  monocytes) or combinations thereof. 
     
     
         23 . The method of  claim 20 , wherein the monocytes are infiltrating monocytes and become OPN expressing macrophages in the brain. 
     
     
         24 . The method of  claim 20 , wherein the innate immune cells are phagocytic. 
     
     
         25 . The method of  claim 20 , wherein the composition comprises glatiramer acetate (GA). 
     
     
         26 . The method of  claim 20 , wherein the innate immune cells are stimulated ex vivo or in vivo. 
     
     
         27 . The method of  claim 20 , wherein innate immune cells expressing OPN are administered to the subject by adoptive cell transfer or bone marrow transplantation. 
     
     
         28 . The method of  claim 27 , wherein the innate immune cells over-express OPN. 
     
     
         29 . The method of  claim 18 , wherein the composition is administered by a method selected from the group consisting of direct delivery to the subject, viral vector delivery, a liposomal delivery system, or nanodrug delivery system. 
     
     
         30 . The method of  claim 18 , wherein the administration of the composition results in an increase in MMP-9. 
     
     
         31 . The method of  claim 18 , wherein increased levels of OPN results in decreased levels of a misfolded protein in the subject, decreased inflammation in the subject, increased synaptic regeneration in the subject, recruitment of macrophages to an amyloid beta (Aβ) plaque site in the subject, or combinations thereof. 
     
     
         32 . The method of  claim 31 , wherein the misfolded protein is Aβ. 
     
     
         33 . The method of  claim 32 , wherein the Aβ is Aβ 40  and/or Aβ 42 .