Adeno‐associated virus‐vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease
Abstract Background A treatment of chronic kidney disease (CKD)‐associated anemia in cats is needed. SB‐001 is an adeno‐associated virus‐vectored (AAV)‐based gene therapeutic agent that is administered intramuscularly, causing the expression of feline erythropoietin. Hypothesis/Objective We hypothes...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Journal of Veterinary Internal Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jvim.16900 |
| _version_ | 1797248103875608576 |
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| author | Shelly L. Vaden Allison R. Kendall Jonathan D. Foster Heidi L. New Jane S. Eagleson Jacky L. May Anne M. Traas Matthew J. Wilson Beth H. McIntyre Christian J. Hinderer Lauren K. Olenick James M. Wilson |
| author_facet | Shelly L. Vaden Allison R. Kendall Jonathan D. Foster Heidi L. New Jane S. Eagleson Jacky L. May Anne M. Traas Matthew J. Wilson Beth H. McIntyre Christian J. Hinderer Lauren K. Olenick James M. Wilson |
| author_sort | Shelly L. Vaden |
| collection | DOAJ |
| description | Abstract Background A treatment of chronic kidney disease (CKD)‐associated anemia in cats is needed. SB‐001 is an adeno‐associated virus‐vectored (AAV)‐based gene therapeutic agent that is administered intramuscularly, causing the expression of feline erythropoietin. Hypothesis/Objective We hypothesized that SB‐001 injection would lead to a sustained increase in PCV in cats with CKD‐associated anemia. Animals Twenty‐three cats with International Renal Interest Society (IRIS) Stage 2 to 4 CKD‐associated anemia were enrolled at 4 veterinary clinics. Methods In a prospective clinical trial, cats were treated with 1 of 3 regimens of SB‐001 (Lo 1.2 × 109 genome copies [GCs] on Day 0; Lo ± Hi [supplemental 2nd dose of 3.65 × 109 GC on Day 42]; Hi 3.65 × 109 GC IM on Day 0) and followed for 70 days. Results A response to SB‐001 at any time between Day 28 and Day 70 was seen in 86% (95% confidence interval 65, 97%) of all cats. There was a significant (P < .003) increase in PCV from Day 0 to Day 28 (mean increase 6 ± 6 percentage points [pp]; n = 21), Day 42 (8 ± 9 pp; n = 21), Day 56 (10 ± 11 pp; n = 17), and Day 70 (13 ± 14 pp, n = 14). Twelve cats were hypertensive at baseline, 4 of which developed encephalopathy during the study. An additional 6 cats became hypertensive during the study. Conclusions and Clinical Importance Results of this study suggest that SB‐001 therapy represents a suitable single injection treatment that can address nonregenerative anemia in cats with CKD. It was generally well tolerated; however, hypertension and encephalopathy developed in some cats as previously described in association with erythropoiesis‐stimulating agent therapy. |
| first_indexed | 2024-03-09T00:19:41Z |
| format | Article |
| id | doaj.art-d00a159ad891407ab4454cf4a78e4c2f |
| institution | Directory Open Access Journal |
| issn | 0891-6640 1939-1676 |
| language | English |
| last_indexed | 2024-04-24T20:09:16Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Veterinary Internal Medicine |
| spelling | doaj.art-d00a159ad891407ab4454cf4a78e4c2f2024-03-23T17:56:17ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762023-11-013762200221010.1111/jvim.16900Adeno‐associated virus‐vectored erythropoietin gene therapy for anemia in cats with chronic kidney diseaseShelly L. Vaden0Allison R. Kendall1Jonathan D. Foster2Heidi L. New3Jane S. Eagleson4Jacky L. May5Anne M. Traas6Matthew J. Wilson7Beth H. McIntyre8Christian J. Hinderer9Lauren K. Olenick10James M. Wilson11Department of Clinical Sciences, College of Veterinary Medicine North Carolina State University Raleigh North Carolina 27607 USADepartment of Clinical Sciences, College of Veterinary Medicine North Carolina State University Raleigh North Carolina 27607 USAFriendship Hospital for Animals Washington DC 20016 USAVCA Sacramento Veterinary Referral Center Sacramento California 95287 USABleecker Street Consulting New York, New York 10012 USAScout Bio, Inc. Philadelphia Pennsylvania 19104 USAScout Bio, Inc. Philadelphia Pennsylvania 19104 USAScout Bio, Inc. Philadelphia Pennsylvania 19104 USABeth Oman Clinical Consulting LLC Kalamazoo Michigan 49004 USAGene Therapy Program, Department of Medicine, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania 19104 USAScout Bio, Inc. Philadelphia Pennsylvania 19104 USAGene Therapy Program, Department of Medicine, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania 19104 USAAbstract Background A treatment of chronic kidney disease (CKD)‐associated anemia in cats is needed. SB‐001 is an adeno‐associated virus‐vectored (AAV)‐based gene therapeutic agent that is administered intramuscularly, causing the expression of feline erythropoietin. Hypothesis/Objective We hypothesized that SB‐001 injection would lead to a sustained increase in PCV in cats with CKD‐associated anemia. Animals Twenty‐three cats with International Renal Interest Society (IRIS) Stage 2 to 4 CKD‐associated anemia were enrolled at 4 veterinary clinics. Methods In a prospective clinical trial, cats were treated with 1 of 3 regimens of SB‐001 (Lo 1.2 × 109 genome copies [GCs] on Day 0; Lo ± Hi [supplemental 2nd dose of 3.65 × 109 GC on Day 42]; Hi 3.65 × 109 GC IM on Day 0) and followed for 70 days. Results A response to SB‐001 at any time between Day 28 and Day 70 was seen in 86% (95% confidence interval 65, 97%) of all cats. There was a significant (P < .003) increase in PCV from Day 0 to Day 28 (mean increase 6 ± 6 percentage points [pp]; n = 21), Day 42 (8 ± 9 pp; n = 21), Day 56 (10 ± 11 pp; n = 17), and Day 70 (13 ± 14 pp, n = 14). Twelve cats were hypertensive at baseline, 4 of which developed encephalopathy during the study. An additional 6 cats became hypertensive during the study. Conclusions and Clinical Importance Results of this study suggest that SB‐001 therapy represents a suitable single injection treatment that can address nonregenerative anemia in cats with CKD. It was generally well tolerated; however, hypertension and encephalopathy developed in some cats as previously described in association with erythropoiesis‐stimulating agent therapy.https://doi.org/10.1111/jvim.16900AAVcatsred blood cellsrenal disease |
| spellingShingle | Shelly L. Vaden Allison R. Kendall Jonathan D. Foster Heidi L. New Jane S. Eagleson Jacky L. May Anne M. Traas Matthew J. Wilson Beth H. McIntyre Christian J. Hinderer Lauren K. Olenick James M. Wilson Adeno‐associated virus‐vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease Journal of Veterinary Internal Medicine AAV cats red blood cells renal disease |
| title | Adeno‐associated virus‐vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease |
| title_full | Adeno‐associated virus‐vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease |
| title_fullStr | Adeno‐associated virus‐vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease |
| title_full_unstemmed | Adeno‐associated virus‐vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease |
| title_short | Adeno‐associated virus‐vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease |
| title_sort | adeno associated virus vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease |
| topic | AAV cats red blood cells renal disease |
| url | https://doi.org/10.1111/jvim.16900 |
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