Therapeutic approaches for treating alzheimer disease and related disorders through a modulation of synapse function

Abstract

The present invention relates to compositions and methods for the treatment of Alzheimer's disease and related disorders. More particularly, the invention relates to combined therapies that modulate synapse function for treating said disease.

1 . A composition comprising zonisamide, or a salt, prodrug, derivative, or sustained release formulation thereof, for treating Alzheimer's disease (AD) in a subject in need thereof 
     
     
         2 . The composition of  claim 1 , further comprising at least one compound selected from the group of dyphylline, tadalafil, argatroban, acamprosate, cinacalcet, terbinafine, cilostazol, baclofen, phenformin, amlodipine and sulfisoxazole, or salts or prodrugs or derivatives or sustained release formulations thereof, for combined, separate or sequential administration with zonisamide. 
     
     
         3 . The composition of  claim 2 , wherein said composition comprises at least one of the following drug combinations, said drugs in each of said combinations being for combined, separate or sequential administration:
 phenformin and zonisamide,   zonisamide and sulfisoxazole,   acamprosate and zonisamide,   zonisamide and dyphylline,   zonisamide and argatroban,   zonisamide and cilostazol, or   zonisamide and terbinafine.   
     
     
         4 . The composition of  claim 2 , wherein said composition further comprises at least one drug that modulates synapse function, for combined, separate or sequential use. 
     
     
         5 . The composition of  claim 2 , wherein said composition further comprises at least one drug that modulates angiogenesis, for combined, separate or sequential use. 
     
     
         6 . The composition of  claim 2 , wherein said composition further comprises at least one drug that modulates cell stress response, for combined, separate or sequential use. 
     
     
         7 . The composition of  claim 1 , which comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         8 . The composition of  claim 1 , wherein said composition is administered repeatedly to the subject. 
     
     
         9 . A composition comprising at least one of the following drug combinations, said drugs in each of said combinations being for combined, separate or sequential administration:
 phenformin and zonisamide,   zonisamide and sulfisoxazole,   acamprosate and zonisamide,   zonisamide and dyphylline,   zonisamide and argatroban,   zonisamide and cilostazol, or   zonisamide and terbinafine.   
     
     
         10 . A composition comprising at least phenformin, or a salt, prodrug, derivative, or sustained release formulation thereof, for treating Alzheimer's disease in a subject in need thereof. 
     
     
         11 . The composition of  claim 10 , wherein said composition comprises at least one of the following drug combinations, said drugs in each of said combinations being for combined, separate or sequential administration:
 phenformin and acamprosate,   phenformin and sulfisoxazole,   phenformin and dyphylline,   phenformin and cilostazol, or   phenformin and tadalafil.   
     
     
         12 . A composition comprising at least one of the following drug combinations, said drugs in each of said combinations being for combined, separate or sequential administration:
 phenformin and acamprosate,   phenformin and sulfisoxazole,   phenformin and dyphylline,   phenformin and cilostazol, or   phenformin and tadalafil.   
     
     
         13 . A method of producing a drug for treating Alzheimer's disease, the method comprising a step of testing a candidate drug for activity on synapse function and selecting candidate drugs that ameliorate synapse function. 
     
     
         14 . A method of treating Alzheimer's disease, the method comprising administering to a subject in need thereof, an effective amount of zonisamide, or a salt or a prodrug or a derivative or a sustained release formulation thereof. 
     
     
         15 . A method of  claim 14 , further comprising simultaneously, separately or sequentially administering to a subject in need thereof, at least one compound chosen from the group consisting of dyphylline, tadalafil, argatroban, acamprosate, cinacalcet, terbinafine, cilostazol, baclofen, phenformin, amlodipine and sulfisoxazole, or salts or prodrugs or derivatives or sustained release formulations thereof.