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 .- 61 . (canceled) 
     
     
         62 . A kit comprising:
 (a) one or more starting unit doses of nicotine or a salt thereof for administration one time to six times a day for about 1 week to about 4 weeks, wherein no more than 1 mg of the nicotine or salt thereof is administered at each administration;   (b) one or more first escalating unit doses of the nicotine or salt thereof for administration one time to six times a day for about 1 week to about 4 weeks, wherein no more than 2 times the one or more starting unit doses of the nicotine or salt thereof is administered at each administration;   (c) optionally, one or more second escalating unit doses of the nicotine or salt thereof for administration one time to six times a day for about 1 week to about 4 weeks, wherein no more than 4 times the one or more starting unit doses of the nicotine or salt thereof is administered at each administration;   (d) optionally, one or more third escalating unit doses of the nicotine or salt thereof for administration one time to four times a day for about 1 week to about 4 weeks, wherein no more than 6 times the one or more starting unit doses of the nicotine or salt thereof is administered at each administration; and   (e) instructions for dose escalation of the nicotine or salt thereof;   wherein a total dose for administration is no more than 24 mg per day.   
     
     
         63 . The kit of  claim 62 , wherein the kit comprises one or more starting unit doses of the nicotine or a salt thereof for administration four times a day for four weeks. 
     
     
         64 . The kit of  claim 63 , wherein the kit comprises a dosage of the nicotine or salt thereof of 112 mg. 
     
     
         65 . The kit of  claim 62 , wherein the nicotine or salt thereof is formulated for oral administration. 
     
     
         66 . The kit of  claim 62 , wherein the nicotine or salt thereof is in solution form. 
     
     
         67 . The kit of  claim 62 , wherein the nicotine or salt thereof is in solid form. 
     
     
         68 . The kit of  claim 62 , wherein the nicotine or salt thereof is in liquid, gel, semi-liquid, semi-solid, or solid form. 
     
     
         69 - 81 . (canceled) 
     
     
         82 . The kit of  claim 62 , comprising (c) one or more second escalating unit doses of the nicotine or salt thereof for administration one time to six times a day for about 1 week to about 4 weeks, wherein no more than 4 times the one or more starting unit doses of the nicotine or salt thereof is administered at each administration. 
     
     
         83 . The kit of  claim 82 , comprising (d) one or more third escalating unit doses of the nicotine or salt thereof for administration one time to four times a day for about 1 week to about 4 weeks, wherein no more than 6 times the one or more starting unit doses of the nicotine or salt thereof is administered at each administration. 
     
     
         84 . The kit of  claim 62 , wherein the one or more starting unit doses are for administration four times a day. 
     
     
         85 . The kit of  claim 84 , wherein the one or more first escalating unit doses are for administration four times a day. 
     
     
         86 . The kit of  claim 85 , wherein the one or more second escalating unit doses are for administration four times a day. 
     
     
         87 . The kit of  claim 86 , wherein the one or more third escalating unit doses are for administration four times a day. 
     
     
         88 . The kit of  claim 62 , wherein about 1 mg of the nicotine or salt thereof is administered at each administration of the one or more starting unit doses. 
     
     
         89 . The kit of  claim 88 , wherein about 2 mg of the nicotine or salt thereof is administered at each administration of the one or more first escalating unit doses. 
     
     
         90 . The kit of  claim 89 , wherein about 4 mg of the nicotine or salt thereof is administered at each administration of the one or more second escalating unit doses. 
     
     
         91 . The kit of  claim 90 , wherein about 6 mg of the nicotine or salt thereof is administered at each administration of the one or more third escalating unit doses. 
     
     
         92 . A kit comprising:
 (a) one or more starting unit doses of nicotine or a salt thereof for administration four times a day for about 1 week to about 4 weeks, wherein no more than 1 mg of the nicotine or salt thereof is administered at each administration;   (b) one or more first escalating unit doses of the nicotine or salt thereof for administration four times a day for about 1 week to about 4 weeks, wherein no more than 2 mg of the nicotine or salt thereof is administered at each administration;   (c) one or more second escalating unit doses of the nicotine or salt thereof for administration four times a day for about 1 week to about 4 weeks, wherein no more than 4 mg of the nicotine or salt thereof is administered at each administration;   (d) one or more third escalating unit doses of the nicotine or salt thereof for administration four times a day for about 1 week to about 4 weeks, wherein no more than 6 mg of the nicotine or salt thereof is administered at each administration; and   (e) instructions for dose escalation of the nicotine or salt thereof;   wherein a total dose for administration is no more than 24 mg per day.   
     
     
         93 . The kit of  claim 92 , wherein the nicotine or salt thereof is formulated for oral administration. 
     
     
         94 . The kit of  claim 92 , wherein the one or more starting unit doses, the one or more first escalation unit doses, the one or more second escalating unit doses, and the one or more third escalating unit doses are each for administration four times a day for about 4 weeks.