US 11,986,659 B2
Modulation of neuronal NKCC1 as a therapeutic strategy for spasticity and related disorders
Zaghloul Ahmed, Staten Island, NY (US)
Assigned to Research Foundation of the City University of New York, New York, NY (US)
Appl. No. 17/040,373
Filed by Research Foundation of the City University of New York, New York, NY (US)
PCT Filed Mar. 22, 2019, PCT No. PCT/US2019/023675
§ 371(c)(1), (2) Date Sep. 22, 2020,
PCT Pub. No. WO2019/183536, PCT Pub. Date Sep. 26, 2019.
Claims priority of provisional application 62/646,574, filed on Mar. 22, 2018.
Prior Publication US 2021/0060341 A1, Mar. 4, 2021
Int. Cl. A61N 1/36 (2006.01); A61K 31/196 (2006.01); A61K 45/06 (2006.01); A61N 1/05 (2006.01); A61N 1/20 (2006.01); A61N 1/24 (2006.01); A61P 25/14 (2006.01)
CPC A61N 1/36121 (2013.01) [A61K 31/196 (2013.01); A61K 45/06 (2013.01); A61N 1/0529 (2013.01); A61N 1/0551 (2013.01); A61N 1/20 (2013.01); A61N 1/24 (2013.01); A61N 1/36062 (2017.08); A61N 1/36157 (2013.01); A61P 25/14 (2018.01)] 8 Claims
OG exemplary drawing
 
1. A system for treatment of at least one of spasticity, hypertonia, dystonia, ALS and neuronal hyperexcitability in a vertebrate being, the system comprising:
a first stimulation component configured to provide peripheral direct current stimulation of a peripheral nerve or nerves associated with at least one of spasticity, hypertonia, dystonia, ALS and neuronal hyperexcitability in a vertebrate being; said first stimulation component including a neural stimulation circuit having at least one neural stimulation pole configured to stimulate at least one said peripheral nerve;
a second stimulation component configured to provide spinal direct current stimulation at a spinal location associated with treatment of said at least one said peripheral nerve, said second stimulation component defining a spinal stimulation circuit having an active spinal stimulation pole and a spinal reference pole, said spinal stimulation circuit configured to provide trans-spinal direct current stimulation between said active spinal stimulation pole and said spinal reference pole for stimulating said spinal location; the active spinal stimulation pole being relatively proximal to said spinal location; the spinal reference pole being relatively distal to said spinal location; and
a controller component configured to ensure that said active spinal stimulation pole and said at least one neural stimulation pole are excited at opposite polarities, and forming a resulting polarization circuit, said resulting polarization circuit being configured to provide a polarizing current flow between said active spinal stimulation pole and said proximal neural pole according to said opposite polarities, for changing biological activity of and/or level of gene expression of and/or protein expression of a target molecule according to said polarizing current flow; said controller component being further configured to provide said polarizing current flow for a predetermined time period to change said at least one of said biological activity, said gene expression, and said protein expression and to achieve at least one of cell proliferation, cell differentiation, cell migration, and cell expression, associated with a treatment delivered for at least one of the neurological conditions including spasticity, hypertonia, dystonia, ALS and neuronal hyperexcitability in said vertebrate being; wherein said target molecule is NKCC1 and wherein the change in said at least one of said biological activity, said gene expression, and said protein expression is one of increased and decreased.