Compositions and methods for treatment related to fall and fall frequency in neurodegenerative diseases

Abstract

The present disclosure provides methods and compositions for treating fall-related symptoms in patients with neurodegenerative diseases such as Parkinson's disease or Parkinson-related diseases. In some embodiments, the disclosure utilizes nicotine or salt thereof in combination of dopaminergic agent treatments for reducing fall-related symptoms such as reducing frequency of fall, reducing injuries related to fall, reducing severity of injuries related to fall, improving posture stability, improving locomotion ability, improving balance and gait. In some embodiments, the methods predict fall frequency and tendency of recurrent falls in patients with Parkinson's disease, in particular, patients with typical Parkinson's disease.

1 .- 118 . (canceled) 
     
     
         119 . A method of treating fall-related symptoms in a subject with neurodegenerative disease, the method comprises administering to the subject a dosage form comprising a nicotinic acetylcholine receptor (nAChR) agonist. 
     
     
         120 . The method of  claim 119 , wherein the nAChR agonist is specific for the α7, β2, or α7 and β2 subunit of the nAChR. 
     
     
         121 . The method of  claim 119 , wherein the nAChR agonist is a full agonist. 
     
     
         122 . The method of  claim 119 , wherein the nAChR agonist is selected from Varenicline, A-85380, sazetidine, TC-2696, TI-10165, TC-8831, TC-10600, ABT-089, ABT-894, AZD1446, ABT-107, AQW051, ABT-894 and ABT-107, 3-Bromocytisine, Acetylcholine, Cytisine, Epibatidine, A-84,543, A-366,833, ABT-418, Altinicline, Dianicline, Ispronicline, Pozanicline, Rivanicline, Tebanicline, TC-1827, Sazetidine A, N-(3-pyridinyl)-bridged bicyclic diamines, (+)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzo[b]furan-2-carboxamide, A-582941, AR-R17779, Amyloid beta, TC-1698, TC-5619, EVP-6124, GTS-21, PHA-543,613, PNU-282,987, PHA-709829, SSR-180,711, Tropisetron, WAY-317,538, Anabasine, and ICH-3. 
     
     
         123 . The method of  claim 119 , wherein the nAChR agonist is selected from ABT-894, ABT-107, TC-8831, ABT-089, AZD1446, and AQW051. 
     
     
         124 . The method of  claim 119 , wherein the nAChR agonist is selected from ABT-894 and ABT-107. 
     
     
         125 . The method of  claim 119 , wherein the fall-related symptoms comprise fall frequency. 
     
     
         126 . The method of  claim 125 , wherein a subject treated with the dosage form comprising the nAChR agonist has a reduced fall frequency. 
     
     
         127 . The method of  claim 119 , wherein the fall-related symptoms comprise frequency of injuries related to fall. 
     
     
         128 . The method of  claim 127 , wherein a subject treated with the dosage form comprising the nAChR agonist has reduced frequency of injuries related to fall. 
     
     
         129 . The method of  claim 119 , wherein the fall-related symptoms comprise severity of fall with injuries. 
     
     
         130 . The method of  claim 129 , wherein a subject treated with the dosage form comprising the nAChR agonist has reduced severity of fall with injuries. 
     
     
         131 . The method of  claim 119 , wherein the subject has recurrent falls. 
     
     
         132 . (canceled) 
     
     
         133 . The method of  claim 119 , wherein improvement of symptoms comprises utilizing one or more of evaluation tests selected from the group consisting of: Unified Parkinson's Disease Rating Scale (UPDRS), Barrow Neurological Institute (BNI) Falls Evaluation, Hoehn & Yahr Staging System, Romberg test, turning test, standing on one leg, tandem gait, step length and velocity. 
     
     
         134 . The method of  claim 119 , wherein the evaluation utilizing the Unified Parkinson's Disease Rating Scale (UPDRS) is selected from the group consisting of: Walking and Balance from questions 2.12 from Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS), Freezing of Gait from questions 2.14 from Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS), Dyskinesias from questions 32-35 from original Unified Parkinson's Disease Rating Scale (UPDRS), Response Fluctuation from questions 36-39 from original Unified Parkinson's Disease Rating Scale (UPDRS), Sleep Disturbance from question 40 from original Unified Parkinson's Disease Rating Scale (UPDRS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS) 142 points, Axial, Midline part of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS), Gait Subtest from Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS, Postural Stability Subtest from Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS), and Freezing of Gait Subtest (FOG) from Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS). 
     
     
         135 . The method of  claim 119 , wherein the improvement of symptoms comprises evaluation utilizing Reason for Fall from the Barrow Neurological Institute (BNI) Falls Evaluation. 
     
     
         136 . The method of  claim 119 , wherein the improvement of symptoms comprises evaluation utilizing Severity of Fall from the Barrow Neurological Institute (BNI) Falls Evaluation. 
     
     
         137 .- 148 . (canceled) 
     
     
         149 . The method of  claim 119 , wherein the subject has Parkinson's disease. 
     
     
         150 . (canceled) 
     
     
         151 . (canceled) 
     
     
         152 . The method of  claim 119  or  137 , wherein the subject has dopaminergic agent treatment. 
     
     
         153 . The method of  claim 152 , wherein said dopaminergic agent is levodopa, carbidopa, dopamine agonist, amantadine, monoamine oxidase B inhibitor, or combination thereof. 
     
     
         154 .- 173 . (canceled)