Treatment of neurodegenerative conditions

Abstract

A method is provided for treating a patient in need of therapy for a neurodegenerative disease comprising administering to that patient a therapeutically effective dose of a triglyceride oil containing both γ-linolenic acid and linoleic acid residues as triglyceride ester, the ratio of γ-linolenic acid to linoleic acid residues at the sn-2 position of the triglyceride being at least 0.8; the amount of γ-linolenic acid residues at the sn-2 position being at least 18%, wherein the oil is administered at a dose sufficient to maintain or elevate TGF-β1 levels in the patient at a therapeutic level. Preferably the method is that wherein the therapeutic level is such as to produce a TGF-β1/TNF-α ratio of at least 0.5 in blood of a patient, after 18 months of daily dosing. Preferred oils are Borage or Mucor oils having at least 35% of the sn-2 position fatty acid residues as γ-linolenic acid.

1 . A method of treating a patient in need of therapy for a neurodegenerative disease comprising administering to that patient a therapeutically effective dose of a triglyceride oil containing both γ-linolenic acid and linoleic acid residues as triglyceride ester, the ratio of γ-linolenic acid to linoleic acid residues at the sn-2 position of the triglyceride being at least 0.8; the amount of γ-linolenic acid residues at the sn-2 position being at least 18%, wherein the oil is administered at a dose sufficient to maintain or elevate TGF-β1 levels in the patient at a therapeutic level. 
     
     
         2 . A method as claimed in  claim 1  wherein the therapeutic level is such as to produce a TGF-β1/TNF-α ratio of at least 0.5 in blood of a patient, after 18 months of daily dosing. 
     
     
         3 . A method as claimed in  claim 2  wherein the ratio is at least 0.75. 
     
     
         4 . A method as claimed in  claim 2  wherein the ratio is at least 1. 
     
     
         5 . A method as claimed in  claim 1  wherein the amount of oil administered is between 3 and 30 grams per day. 
     
     
         6 . A method as claimed in  claim 1  wherein the oil is administered orally. 
     
     
         7 . A method as claimed in  claim 1  wherein the dose is sufficient to administer at least 1 gram of γ-linolenic acid residues, as residues in the sn-2 position, excluding other γ-linolenic acid content of the oil. 
     
     
         8 . A method as claimed in  claim 1  wherein the amount of γ-linolenic acid in the sn-2 position in the dose of oil is sufficient to administer at least 2 grams of said sn-2 γ-linolenic acid. 
     
     
         9 . A method as claimed in  claim 1  wherein the dose is between 8 and 20 grams. 
     
     
         10 . A method as claimed in  claim 1  wherein in addition to the γ-linolenic acid and linolenic acid fatty acid residues, the triglyceride includes an esterified fatty acid that is non-structural. 
     
     
         11 . A method as claimed in  claim 10  wherein the triglyceride contains oleic acid residues. 
     
     
         12 . A method as claimed in  claim 1  wherein the oil is that obtained from a fungus or a plant selected from the group consisting of  Mucor  and  Borago  species. 
     
     
         13 . A method as claimed in  claim 1  wherein the fungus or plant is selected from  Mucor javanicus  and  Borago officianalis.    
     
     
         14 . A method as claimed in  claim 1  wherein the oil is a Borne oil in which the percentage of esterified γ-linolenic acid at the sn-2 position is at least 35% of fatty acid residues at that position. 
     
     
         15 . A method as claimed in  claim 14  wherein the percentage of esterified γ-linolenic acid at the sn-2 position is at least 39% of fatty acid residues at that position. 
     
     
         16 . A method as claimed in  claim 14  wherein the percentage of esterified γ-linolenic acid at the sn-2 position is at least 45% of fatty acid residues at that position. 
     
     
         17 . A method as claimed in  claim 1  wherein the fatty acid residues in the sn-1 and sn-3 position include linoleic, oleic and γ-linolenic acid residues. 
     
     
         18 . A method as claimed in  claim 1  wherein the triglyceride oil has an oleic acid content in one or both of the sn-1 and sn-3 positions of in excess of 12%. 
     
     
         19 . A method as claimed in  claim 1  wherein the oil is Mucor oil and, the total percentage of esterified γ-linolenic acid residues at the sn-2 position is at least 20% of fatty acid residues at that position. 
     
     
         20 . A method as claimed in  claim 19  wherein the triglyceride oil has in excess of 45% of the sn-2 fatty acid residues as oleic acid residues. 
     
     
         21 . A method as claimed in  claim 19  wherein the triglyceride oil has in excess of 50% of the sn-2 fatty acids as oleic acid residues. 
     
     
         22 . A method as claimed in  claim 1  wherein the triglyceride oil contains less than 5% monoenoic fatty acid residues as % total fatty acid residues. 
     
     
         23 . A method as claimed in  claim 22  wherein the triglyceride oil contains less than 5% in total erucic acid (22:1n-9), 24:1n-9 (nervonic acid) and 20:1n-9 (gadoleic acid) as a percentage of total fatty acid residues. 
     
     
         24 . A method as claimed in  claim 22  wherein the amount of said acid is between 1° A) and 5% of fatty acid residues in the oil. 
     
     
         25 . A method as claimed in  claim 1  wherein the oil has no added vitamin E. 
     
     
         26 . A method as claimed in  claim 1  wherein the amount of Vitamin E is between 0 and 0.1 mg/g. 
     
     
         27 . A method as claimed in  claim 1  wherein the neurodegenerative disease is arrested or neuronal function is restored. 
     
     
         28 . A method as claimed in  claim 1  wherein treatment is for multiple sclerosis or the degenerative sequelae associated with head trauma, stroke and intracranial bleeds. 
     
     
         29 . A method as claimed in  claim 28  wherein the treatment repairs lesions. 
     
     
         30 . A method as claimed in  claim 1  wherein the treatment uses a dose sufficient to relieve muscle spasticity and/or pain. 
     
     
         31 . A method as claimed in  claim 1  wherein the dosage is sufficient to improve cognitive function. 
     
     
         32 . A method as claimed in  claim 1  wherein the dosage is sufficient to eliminate relapses. 
     
     
         33 . A method as claimed in  claim 1  wherein the dosage is sufficient to improve the patients EDSS score by at least 1 unit over a period of 1 years treatment. 
     
     
         34 . A method as claimed in  claim 1  wherein the dosage is sufficient to restore EDSS of a patient with EDSS above 2.5 to below 2 over a period of 1 years treatment. 
     
     
         35 . Use of an oil as described in  claim 1  for the manufacture of a medicament for the treatment of neurodegenerative 
     
     
         36 . A pharmaceutical composition for the treatment of neurodegenerative disease comprising a  Borago  or  Mucor  species triglyceride oil as described in  claim 14 .