Methods of treating proteinopathy associated wandering

Abstract

The invention is based on the discovery that rho kinase inhibitors can be used to treat proteinopathy associated wandering. A number of degenerative neurological diseases are thought to be caused, at least in part, by the formation of protein aggregates that cause neurotoxicity and progressive decline in function. The inventive methods related to the use of rho kinase inhibitors in the treatment of patients with proteinopathy-associated wandering. The patients may be suffering from Huntington's disease, a traumatic brain injury, autism spectrum disorder, Down syndrome or a proteinopathy-associated dementia, such as Alzheimer disease or frontotemporal dementia.

1 . A method of treating wandering in a patient with proteinopathy-associated disease, comprising administering a therapeutically effective amount of a rho kinase inhibitor to the patient, wherein the disease is selected from the group consisting of Huntington's disease, Parkinson's disease, Down Syndrome, progressive supranuclear palsy, and frontotemporal dementia. 
     
     
         2 . The method according to  claim 1 , wherein the patient has Huntington's disease or Parkinson's disease. 
     
     
         3 . The method according to  claim 1  wherein the patient has wandering due to dementia. 
     
     
         4 . The method according to  claim 3  wherein the patient has wandering due to frontotemporal dementia. 
     
     
         5 . The method according to  claim 3  wherein the patient does not have vascular dementia. 
     
     
         6 . The method according to  claim 1  wherein the patient suffers from persistent wandering. 
     
     
         7 . The method according to  claim 4  wherein the patient moves at least 20% of their waking time. 
     
     
         8 . The method according to  claim 1  wherein the patient does not exhibit problems with wayfinding. 
     
     
         9 . The method according to  claim 1  wherein the treatment results in a greater-than 3-point improvement on the mini mental state exam. 
     
     
         10 . The method according to  claim 5 , wherein the treatment results in at least a 50% reduction in the time the patient is in motion. 
     
     
         11 . The method according to  claim 1  wherein the rho kinase inhibitor is an isoquinolone derivative. 
     
     
         12 . The method according to  claim 9  wherein the isoquinolone derivative is fasudil, a salt, or a derivative thereof. 
     
     
         13 . The method according to  claim 9  wherein the derivative is M3. 
     
     
         14 . The method according to  claim 1  where the treatment continues for at least 6 months. 
     
     
         15 . The method according to  claim 10 , wherein the isoquinolone derivative is administered in a dose exceeding 60 mg per day. 
     
     
         16 . The method according to  claim 13 , wherein the dose is administered in three equal portions throughout the day. 
     
     
         17 . The method according to  claim 14 , wherein the total daily dose is between 70 mg and 120 mg. 
     
     
         18 . The method according to  claim 13 , wherein the total daily dose exceeds 70 mg and is administered in a sustained release formulation. 
     
     
         19 . The method according to  claim 1 , wherein the proteinopathy is characterized by deposits containing the huntingtin protein, FUS, TDP-43, β-amyloid, tau, optineurin, ubiquitin 2, superoxide dismutase 1, neurogenic locus notch homolog protein 3 and/or α-synuclein.