Treatment of pyrroline-5-carboxylate reductase 1 (PYCR1) related disease by inhibition of natural antisense transcript to PYCR1

A method of selecting a modified antisense oligonucleotide which can modulate a function of and/or the expression of a Pyrroline-5-carboxylate reductase 1 (PYCR1) polynucleotide in patient cells or tissues in vivo or in vitro comprising:

• selecting at least one modified antisense oligonucleotide of 10 to 30 nucleotides in length which is at least 90% complementary to a region of a natural antisense polynucleotide the PYCR1 polynucleotide;
• contacting said at least one modified antisense oligonucleotide with said natural antisense polynucleotide to form a hybrid;
• measuring the thermal melting point of the hybrid of the at least one modified antisense oligonucleotide with said natural antisense polynucleotide under stringent hybridization conditions;
• selecting at least one modified antisense oligonucleotide having binding affinity to said natural antisense polynucleotide based upon the thermal melting point results;
• determining the modulation activity of the selected at least one modified antisense oligonucleotide having binding affinity to said natural antisense polynucleotide and
• selecting at least one modified antisense oligonucleotide which modulates a function of and/or expression of the PYCR1 polynucleotide wherein the at least one modified antisense oligonucleotide comprises one or more modifications selected from:
• at least one modified sugar moiety, at least one modified intemucleoside linkage, at least one modified nucleotide, and combinations thereof.