Abstract: Minoxidil has been shown to stimulate hair growth or inhibit the loss of hair in a number of patients beginning to develop androgenic alopecia. The mechanism by which minoxidil (2,4-pyrimidinediamine, 6-(1-piperidinyl)-3-oxide) alters the hair growth cycle is uncertain, but is thought to act by increasing vascular circulation to the hair follicle. Inhibitors of steroid metabolism, particularly those that inhibit the conversion of testosterone to dihydrotestosterone, have shown effects on hair cycles, including inhibition of hair loss. One class of enzymes targeted by these inhibitors are the steroid 5-alpha reductases. Minoxidil used in conjunction with effectors of steroid metabolism, leads to enhanced hair growth and decreased rates of hair loss. This specification relates to the use of antisense oligonucleotides targeting 5-alpha reductases used in conjunction with other hair growth enhancers and/or hair loss inhibitors.

Abstract: (2'-5') linked 3'-Deoxyoligodeoxynucleotides have been synthesized on a solid support via standard cyanoethyl phosphoramidite chemistry. This simple change in the oligonucleotide bond connectivity leads to unique properties. Thus (2'-5') 3'-deoxyoligodeoxynucleotides hybridize selectively to single stranded RNA but not DNA. The (2'-5') linkages confer greater resistance to exo- and endonyucleolytic degradation compared to (3'-5') -linked oligomers. In addition, (2'-5') linked 3'-deoxyoligodeoxynucleotides support RNase-H activity. The nucleic acid selectivity of (2'-5')oligo-3'0-deoxynucleotides may represent an important design feature to improve the efficacy of antisense oligonucleotides.