Methods of treating amyotrophic lateral sclerosis
Disclosed are methods for inhibiting the progression of neurodegenerative disease. The methods include administering to a patient suffering from such a disease a composition comprising either deuterated linoleic acid or an ester thereof.
1 . A method for reducing disease progression of a neurodegenerative disease treatable with 11,11-D2-linoleic acid in a patient, comprising:
administering 11,11-D2-linoleic acid or an ester thereof to the patient with a dosing regimen that comprises a primer dose and a maintenance dose thereby reducing the disease progression in the patient, wherein:
a) the primer dose comprises periodic administration of from about 7 to 12 grams of 11,11-D2-linoleic acid or an ester thereof per day, wherein the primer dose is continued for about 30 days to about 45 days to rapidly achieve a therapeutic concentration of 13,13-D2-arachidonic acid in vivo; and
b) subsequent to completion of the primer dose, periodically administering the maintenance dose of no more than about 65% of the primer dose of 11,11-D2-linoleic acid or an ester thereof per day thereof to maintain the therapeutic concentration of 13,13-D2-arachidonic acid in vivo, such that a rate of disease progression is reduced, wherein the neurodegenerative disease is mediated at least in part by lipid peroxidation of polyunsaturated fatty acids in neurons of the patient;
wherein the disease is amyotrophic lateral sclerosis, Huntington's Disease, progressive supranuclear palsy (PSP), Friedreich's ataxia, APO-e4 Alzheimer's Disease, corticobasal disorder (CBD), frontotemporal dementia (FTD), nonfluent variant primary progressive aphasia (nfvPPA), other tauopathies, and late onset Tay-Sachs.
2 . The method of claim 1 , wherein the periodic administration of the primer dose comprises administration of about 9 grams of 11,11-D2-linoleic acid or an ester thereof per day for at least 5 days per week.
3 . The method of claim 1 , wherein the periodic administration of the primer dose comprises administration of about 9 grams of 11,11-D2-linoleic acid or a C1-C6 alkyl ester thereof per day for each day.
4 . The method of claim 1 , wherein the periodic administration of the maintenance dose comprises no more than 55% of the primer dose which is administered at least once a month.
5 . The method of claim 4 , wherein the periodic administration of the maintenance dose comprises no more than 35% of the primer dose which is administered at least once a week.
6 . The method of claim 5 , wherein the periodic administration of the maintenance dose is calibrated to be an amount of 11,11-D2-linoleic acid or an ester thereof sufficient to replace the amount of 13,13-D2-arachidonic acid removed by conversion of a portion of 11,11-D2-linoleic acid to 13,13-D2-arachidonic acid.
7 . The method of claim 6 , wherein the periodic administration of the maintenance dose comprises is administered at least once a month.
8 . The method of claim 1 , wherein a percent reduction in the rate of disease progression is determined by:
measuring a natural rate of disease progression in a patient or an average natural rate of disease progression in a cohort of patients;
measuring the rate of disease progression in the patient or cohort of patients during a period of compliance with the administering; and after 1 month or 3 months since the onset of therapy, calculating the difference between the natural rate and a rate during the period of compliance, dividing the difference by the rate of disease progression during the natural history of the patient, and multiplying by 100.
9 . The method of claim 1 , which further comprises restricting the the patient from consuming excessive dietary polyunsaturated fatty acids during administration of the primer and the maintenance doses.
10 . The method of claim 1 , wherein the primer dose and/or the maintenance dose is provided in 1, 2 or 3 administrations during a single day.
11 . The method of claim 1 , wherein the neurodegenerative disease is amyotrophic lateral sclerosis, Huntington's Disease, progressive supranuclear palsy (PSP), Friedreich's ataxia, or APO-e4 Alzheimer's Disease.