Use of lipid conjugates in the treatment of diseases of the nervous system

A method of ameliorating damage to the nervous system in a subject suffering from multiple sclerosis in need thereof, comprising administering to said subject an effective amount of a conjugate having the general structure of formula (II):

• wherein
• R1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• R2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof;
• wherein if Y is nothing the phospholipid moiety is directly linked to X via an amide bond and if Y is a spacer group, the spacer group is directly linked to X via an amide or an ester bond and to the phospholipid moiety via an amide bond;
• X is a glycosaminoglycan;
• and
• n is the number of lipid moiety molecules bound to a molecule of X wherein n is a number from 1 to 1000;
• wherein said damage to the nervous system in said subject is ameliorated.

A method of ameliorating damage to the nervous system in a subject suffering from multiple sclerosis in need thereof, comprising administering to said subject an effective amount of a conjugate having the general structure of formula (III):

• wherein
• R1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• R2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• Z is either nothing, inositol, choline, or glycerol;
• Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof;
• wherein if Y is nothing the phospholipid moiety is directly linked to X via an amide bond and if Y is a spacer group, the spacer group is directly linked to X via an amide or an ester bond and to the phospholipid moiety via an amide bond;
• X is a glycosaminoglycan;
• and
• n is the number of lipid moiety molecules bound to a molecule of X wherein n is a number from 1 to 1000;
• wherein said damage to the nervous system in said subject is ameliorated.

A method of ameliorating damage to the nervous system in a subject suffering from multiple sclerosis in need thereof, comprising administering to said subject an effective amount of a conjugate having the general structure of formula (IV):

• wherein
• R1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• R2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol;
• Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof;
• wherein if Y is nothing the phospholipid moiety is directly linked to X via an amide bond and if Y is a spacer group, the spacer group is directly linked to X via an amide or an ester bond and to the phospholipid moiety via an amide bond;
• X is a glycosaminoglycan;
• and
• n is the number of lipid moiety molecules bound to a molecule of X wherein n is a number from 1 to 1000;
• wherein said damage to the nervous system in said subject is ameliorated.

A method of ameliorating damage to the nervous system in a subject suffering from multiple sclerosis in need thereof, comprising administering to said subject an effective amount of a conjugate having the general structure of formula (V):

• wherein
• R1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• R2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol;
• Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof;
• wherein if Y is nothing the phospholipid moiety is directly linked to X via an amide bond and if Y is a spacer group, the spacer group is directly linked to X via an amide or an ester bond and to the phospholipid moiety via an amide bond;
• X is a glycosaminoglycan;
• and
• n is the number of lipid moiety molecules bound to a molecule of X wherein n is a number from 1 to 1000;
• wherein said damage to the nervous system in said subject is ameliorated.

A method of ameliorating damage to the nervous system in a subject suffering from multiple sclerosis in need thereof, comprising administering to said subject an effective amount of a conjugate having the general structure of formula (VI):

• wherein
• R1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• R2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• Z is either nothing, ethanolamine, serine, inositol, choline, or glycerol;
• Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof;
• wherein if Y is nothing the phospholipid moiety is directly linked to the glycosaminoglycan via an amide bond and if Y is a spacer group, the spacer group is directly linked to the glycosaminoglycan via an amide or an ester bond and to the phospholipid moiety via an amide bond;
• X is a glycosaminoglycan;
• and
• n is the number of lipid moiety molecules bound to a molecule of X wherein n is a number from 1 to 1000;
• wherein said damage to the nervous system in said subject is ameliorated.

A method of ameliorating damage to the nervous system in a subject suffering from multiple sclerosis in need thereof, comprising administering to said subject an effective amount of a conjugate having the general structure of formula (VII):

• wherein
• R1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof;
• wherein if Y is nothing the lipid moiety is directly linked to the glycosaminoglycan via an amide bond and if Y is a spacer group, the spacer group is directly linked to the glycosaminoglycan via an amide or an ester bond and to the lipid moiety via an amide bond;
• X is a glycosaminoglycan;
• and
• n is the number of lipid moiety molecules bound to a molecule of X wherein n is a number from 1 to 1000;
• wherein said damage to the nervous system in said subject is ameliorated.

A method of ameliorating damage to the nervous system in a subject suffering from multiple sclerosis in need thereof, comprising administering to said subject an effective amount of a conjugate having the general structure of formula (VIII):

• wherein
• R1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• R2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• Z is either ethanolamine, serine, inositol, choline, or glycerol;
• Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof;
• wherein if Y is nothing the lipid moiety is directly linked to the glycosaminoglycan via an amide bond and if Y is a spacer group, the spacer group is directly linked to the glycosaminoglycan via an amide or an ester bond and to the lipid moiety via an amide bond;
• X is a glycosaminoglycan;
• and
• n is the number of lipid moiety molecules bound to a molecule of X wherein n is a number from 1 to 1000;
• wherein said damage to the nervous system in said subject is ameliorated.

A method of ameliorating damage to the nervous system in a subject suffering from multiple sclerosis in need thereof, comprising administering to said subject an effective amount of a conjugate having the general structure of formula (IX):

• wherein
• R1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• R2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;
• Z is either choline, phosphate, inositol, or glycerol;
• Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof;
• wherein if Y is nothing the lipid moiety is directly linked to the glycosaminoglycan via an amide bond and if Y is a spacer group, the spacer group is directly linked to the glycosaminoglycan via an amide or an ester bond and to the lipid moiety via an amide bond;
• X is a glycosaminoglycan;
• and
• n is the number of lipid moiety molecules bound to a molecule of X wherein n is a number from 1 to 1000;
• wherein said damage to the nervous system in said subject is ameliorated.