WVE-006, an advanced candidate for treating alpha-1 antitrypsin deficiency (AATD), is designed to restore functional wild-type AAT protein production and reduce Z-AAT protein aggregation. The agent has the therapeutic potential for disease modification in both lung and liver phenotypes of AATD. 

Last month, the clinical-stage genetic medicines company Wave Life Sciences hosted a virtual event, “Toward the Clinic: Spotlight on RNA Editing for AATD.” At the event, the company discussed WVE-006, their preclinical A-to-I RNA base-editing oligonucleotide (“AIMer”) candidate to treat AATD.

As an N-acetylgalactosamine-conjugated RNA-editing candidate, WVE-006 is currently in development to use an oligonucleotide to harness an endogenous enzyme for editing. It is designed to correct the single G-to-A base mutation in mRNA that is coded by the SERPINA 1 Z allele, thus facilitating the production of functional, wild-type M-AAT protein.


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In addition, future therapeutic applications of the company’s RNA-editing capabilities, including modulating protein interactions and addressing diseases outside the liver, were discussed.

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Key takeaways on WVE-006 included:

  • AAT protein levels in mice that received WVE-006 were about 7-fold higher than those in phosphate-buffered saline-administered controls.
  • Treatment with WVE-006 was associated with the restoration of approximately 50% of wild-type M-AAT protein in serum.
  • A 3-fold increase in neutrophil elastase inhibition activity was observed with WVE-006, thus demonstrating that the restored M-AAT protein was functional.

“RNA editing is emerging as a distinct class of therapeutics with potential to address disease biology in novel and innovative ways and reach patients [with] an array of diseases, including neurological disorders, as well as renal, cardiometabolic, or immunologic diseases,” said Paul Bolno, MD, MBA, president and chief executive officer of Wave Life Sciences.

Reference

Wave Life Sciences highlights therapeutic potential for WVE-006 for alpha-1 antitrypsin deficiency and progress bringing RNA editing to the clinic during analyst and investor event. News release. Wave Life Sciences; September 28, 2022.