Methods of treatment of chronic kidney disease
AssigneeAstraZeneca AB
InventorsLisa BUVALL, Lars Anders DAHLÉN, Hans Fredrik KARLSSON, Alex Xianghua ZHOU, Hanna WALLENTIN, Karl Henrik EDMAN, Stefan GESCHWINDNER, Mats Fredrik ORMO
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Abstract
The application relates to methods of treating chronic kidney disease in a patient in need thereof involving administering an inhibitor of ARGHEF6 activity such as an antisense oligonucleotide. Use of ARHGEF6 inhibitors in medicine and in the manufacture of medicines are also disclosed.
Claims14
An ARHGEF6 specific antisense oligonucleotide for use in the treatment or prophylaxis of chronic kidney disease.
An ARHGEF6 specific antisense oligonucleotide for use according to any preceding claim, produced by a process comprising the steps of a) selecting a ASO that targets an accessible region of ARHGEF6, optionally a region of ARHGEF6 having an accessibility score>0.001 as determined using the Vienna RNA RNAplfold algorithm;
- b) determining that the candidate ASO has perfect complementarity to only the ARHGEF6 sequence;
- c) determining that the candidate ASO has complementarity with 1 mismatch to no greater than 50 other genes;
- d) filtering to remove ASOs that target a region with a minor allele frequency of >0.05, and e) further filtering to remove ASOs that have CG motifs and has a % GC content of <10
A method of treatment or prophylaxis comprising administering an effective amount of an ARHGEF6 specific antisense oligonucleotide to a patient in need thereof, wherein the patient in need thereof has chronic kidney disease or has been identified as being at risk of developing chronic kidney disease.
An ARHGEF6 specific antisense oligonucleotide for use in the manufacture of a medicament for the treatment or prophylaxis of chronic kidney disease.
A process for producing an ARHGEF6 specific antisense oligonucleotide comprising the steps of:
- a) selecting an antisense oligonucleotide that targets an accessible region of ARHGEF6, optionally a region of ARHGEF6 having an accessibility score>0.001 as determined using the Vienna RNA RNAplfold algorithm;
- b) determining that the candidate antisense oligonucleotide has perfect complementarity to only the ARHGEF6 sequence;
- c) determining that the candidate antisense oligonucleotide has complementarity with 1 mismatch to no greater than 50 other genes;
- d) filtering to ensure that the candidate antisense oligonucleotide does not target a region with a minor allele frequency of >0.05;
- e) ensuring that the candidate antisense oligonucleotide has no CG motifs and has a % GC content of >10;
- and
- f) synthesising the resultant oligonucleotide.
Dependencies are inferred from the claim text.