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 a 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, freezing of gait, 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 - 77 . (canceled) 
     
     
         78 . A method of administering nicotine or a salt thereof to a subject in need thereof, comprising:
 (a) administering a starting dose of the nicotine or salt thereof one time to six times a day for about 1 week to about 4 weeks, wherein the starting dose is about 1 mg;   (b) administering a first escalating dose of the nicotine or salt thereof one time to six times a day for about 1 week to about 4 weeks, wherein the first escalating dose of the nicotine or salt thereof is about 2 mg;   (c) optionally, administering a second escalating dose of the nicotine or salt thereof one time to six times a day for about 1 week to about 4 weeks, wherein the second escalating dose of the nicotine or salt thereof is about 4 mg;   (d) optionally, administering a third escalating dose of the nicotine or salt thereof one time to four times a day for about 1 week to about 4 weeks, wherein the third escalating dose of the nicotine or salt thereof is about 6 mg; and   (e) evaluating one or more parameters;
 wherein a total dose for administration is no more than 24 mg per day. 
   
     
     
         79 . The method of  claim 78 , wherein the one or more parameters is an adverse event. 
     
     
         80 . The method of  claim 78 , wherein the subject is evaluated for the one or more parameters using laboratory tests, mental evaluation tests, or physical evaluation tests. 
     
     
         81 . The method of  claim 78 , wherein the method does not result in tolerance or dependence on the nicotine or salt thereof. 
     
     
         82 . The method of  claim 79 , wherein the adverse event is selected from nausea, dizziness, constipation, vomiting, fatigue, pain, diarrhea, headache, pain in extremity, tremor, nightmare, and insomnia. 
     
     
         83 . The method of  claim 78 , comprising (c) administering the second escalating dose of the nicotine or salt thereof one time to six times a day for about 1 week to about 4 weeks, wherein the second escalating dose of the nicotine or salt thereof is about 4 mg. 
     
     
         84 . The method of  claim 83 , comprising (d) administering the third escalating dose of the nicotine or salt thereof one time to four times a day for about 1 week to about 4 weeks, wherein the third escalating dose of the nicotine or salt thereof is about 6 mg. 
     
     
         85 . The method of  claim 84 , comprising administering the second escalating dose of the nicotine or salt thereof one time to six times a day for about 1 week to about 4 weeks if the subject does not tolerate the third escalating dose of the nicotine or salt thereof due to nausea or vomiting, wherein the second escalating dose of the nicotine or salt thereof is about 4 mg. 
     
     
         86 . The method of  claim 78 , comprising adjusting the first escalating dose, the second escalating dose or the third escalating dose downward to the starting dose, the first escalating dose or the second escalating dose, respectively, if the first escalating dose, the second escalating dose or the third escalating dose is not tolerated due to nausea or vomiting, and administering the adjusted dose to the subject chronically. 
     
     
         87 . The method of  claim 78 , comprising administering the starting dose of the nicotine or salt thereof four times a day. 
     
     
         88 . The method of  claim 78 , comprising administering the first escalating dose of the nicotine or salt thereof four times a day. 
     
     
         89 . The method of  claim 78 , comprising administering the second escalating dose of the nicotine or salt thereof four times a day. 
     
     
         90 . The method of  claim 78 , comprising administering the third escalating dose of the nicotine or salt thereof four times a day. 
     
     
         91 . The method of  claim 78 , comprising administering the starting dose of the nicotine or salt thereof four times a day, administering the first escalating dose of the nicotine or salt thereof four times a day, administering the second escalating dose of the nicotine or salt thereof four times a day, and administering the third escalating dose of the nicotine or salt thereof four times a day. 
     
     
         92 . The method of  claim 78 , wherein the nicotine or salt thereof is formulated for oral administration. 
     
     
         93 . The method of  claim 78 , wherein the method reduces falls in the subject. 
     
     
         94 . The method of  claim 78 , wherein the subject has Parkinson's disease. 
     
     
         95 . The method of  claim 94 , wherein the subject is on levodopa treatment. 
     
     
         96 . The method of  claim 95 , wherein the method reduces falls in the subject. 
     
     
         97 . A method of administering nicotine or a salt thereof to a subject in need thereof, comprising:
 (a) administering a starting dose of the nicotine or salt thereof one time to six times a day for about 1 week to about 4 weeks, wherein the starting dose is no more than 1 mg;   (b) administering a first escalating dose of the nicotine or salt thereof one time to six times a day for about 1 week to about 4 weeks, wherein the first escalating dose of the nicotine or salt thereof is no more than 2 times the starting dose;   (c) optionally, administering a second escalating dose of the nicotine or salt thereof one time to six times a day for about 1 week to about 4 weeks, wherein the second escalating dose of the nicotine or salt thereof is no more than 4 times the starting dose;   (d) optionally, administering a third escalating dose of the nicotine or salt thereof one time to four times a day for about 1 week to about 4 weeks, wherein the third escalating dose of the nicotine or salt thereof is no more than 6 times the starting dose; and   (e) evaluating one or more parameters;
 wherein a total dose for administration is no more than 24 mg per day.