Method of inhibiting biosynthesis of EIf5A

A method for the inhibition or prevention of the intracellular biosynthesis of Elf5A comprising administering to a human or non-human mammal in need thereof an amount of a polyamine sufficient to deplete the supply of intracellular spermidine required for Elf5A biosynthesis, but insufficient to substantially affect polyamine homeostasis, said polyamine having one of the formulae:

• wherein:
• R1 and R6 may be the same or different and are H, alkyl or aralkyl having from 1 to 12 carbon atoms, provided that, in formula (I), R1 and R6 are not H;
• R2-R5 may be the same or different and are H, R1 or R6;
• R7 is H, alkyl, aryl or aralkyl having from 1 to 12 carbon atoms;
• m is an integer from 3 to 6, inclusive;
• n is an integer from 3 to 6, inclusive;
• v, w, x, y and z may be the same or different and are integers from 3 to 10, inclusive;
• or its stereoisomers wherein:
• R8-R13 may be the same or different and are alkyl, branched alkyl, aryl, arylalkyl, cycloalkyl, optionally having an alkyl chain interrupted by at least one etheric oxygen atom, or hydrogen;
• N1, N2, N3 and N4 are nitrogen atoms capable of protonation at physiological pH's;
• a and b may be the same or different and are integers from 1 to 4, with the proviso that one, but not both, of a and b may be 0;
• A, B and C may be the same or different and are bridging groups which effectively maintain the distance between the nitrogen atoms such that the polyamine:
• (i) is capable of uptake by a target cell upon administration of the polyamine to a human or non-human mammal or is capable of binding to at least one polyamine site of a receptor located within or on the surface of a cell upon administration of the polyamine to a human or non-human mammal;
• and
• (ii) upon uptake by the target cell, competitively binds via an electrostatic interaction between the positively charged nitrogen atoms to biological counter-anions;
• the polyamine, upon binding to the biological counter-anion in the cell, functions in a manner substantially biologically different than the intracellular polyamines;
• and
• further wherein at least one of said bridging groups A, B and C may contain at least one —CH(OH)— group which is not alpha- to either of the nitrogen atoms;
• or
• (V) a salt thereof with a pharmaceutically acceptable acid.