Therapeutic Use of IgA protease
As a primary glomerulonephritis, immunoglobulin A (IgA) nephropathy is caused by deposition of clumps of antibodies (poly-IgA complexes). IgA nephropathy (IgAN) has a variable course of clinical progression with a high risk of kidney failure. Although there is no specific management strategy, enzymatic removal of accumulated IgA is being investigated to treat rapidly progressive IgA nephropathy. Recombinant IgA proteases derived from bacterial, which perform substrate specificity for human IgA, is under pre-clinical research.
AK183 (formerly PKU308) is an IgA protease from Clostridium ramosum, initially found by Peking University. IgA protease is also known as IgA degrading enzyme. The fusion protein Fc-AK183 has been reported to be effective to destroy IgA and remove pathological deposits from the mice kidney. IgA-degrading enzymes are promising therapeutic candidates for IgA nephropathy.
It is noted that, fusion protein Fc-AK183 expressed in HEK293 fails to hydrolyse IgA. While recombinant Fc-AK183 produced in Escherichia coli (E. coli) can avoid this problem.
IGAN Biosciences is developing a recombinant Haemophilus influenzae IgA protease for treatment of IgA nephropathy. The recombinant form of IgA protease is expressed in E. coli. In preliminary studies, researchers found that recombinant IgA protease successfully clear IgA complexes in the kidney.
Yaohai Bio-Pharma Offers One-Stop CDMO Solution for IgA protease
IgA Protease pipelines
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Generic Name
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Brand Name/ Altermative Name
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Expression System
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Indications
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Manufacturer
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R&D Stage
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IgA protease, recombinant
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Haemophilus influenzae derived IgA protease
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E. coli
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IgA nephropathy (IgAN)
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IGAN Biosciences, BioMarin
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Pre-clinical
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IgA protease fusion protein
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PKU308/AP308, Clostridium ramosum derived IgA protease
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E. coli
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IgA nephropathy (IgAN)
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Alebund Pharmaceuticals, Alezyme, Peking University
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Pre-clinical
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Reference:
[1] Carney EF. A recombinant fusion protein clears IgA deposits. Nat Rev Nephrol. 2022 May;18(5):273. doi: 10.1038/s41581-022-00568-x.
[2] Xie X, Li J, Liu P, Wang M, Gao L, Wan F, Lv J, Zhang H, Jin J. Chimeric Fusion between Clostridium Ramosum IgA Protease and IgG Fc Provides Long-Lasting Clearance of IgA Deposits in Mouse Models of IgA Nephropathy. J Am Soc Nephrol. 2022 May;33(5):918-935. doi: 10.1681/ASN.2021030372.
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