Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy
Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implica...
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| Veröffentlicht in: | Molecular therapy. Methods & clinical development 2023-12, Vol.31, p.101117-101117, Article 101117 |
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| container_title | Molecular therapy. Methods & clinical development |
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| creator | Day, John W. Mendell, Jerry R. Burghes, Arthur H.M. van Olden, Rudolf W. Adhikary, Rishi R. Dilly, Keith W. |
| description | Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implications. We conducted a retrospective study to describe the seroprevalence of anti-AAV9 binding antibodies for pediatric patients with SMA in the United States. At initial testing, 13.0% (115 of 882) of patients (mean [SD] age, 26.29 [33.66] weeks) had elevated AAV9-Ab titers. The prevalence of elevated titers decreased as age increased, with 18.2% (92 of 507) of patients ≤3 months old but only 1.1% (1 of 92) of patients ≥21 months old having elevated titers. This suggests transplacental maternal transfer of antibodies. No patterns of geographic variations in AAV9-Ab prevalence were confirmed. Elevated AAV9-Ab titers in children |
| doi_str_mv | 10.1016/j.omtm.2023.101117 |
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Day and colleagues describe the seroprevalence of anti-adeno-associated virus serotype 9 vector antibodies (AAV9-Ab), which has safety and efficacy considerations for spinal muscular atrophy (SMA) gene therapy with onasemnogene abeparvovec. Elevated AAV9-Ab concentrations were infrequent for children with SMA and decreased over time, allowing eventual administration of onasemnogene abeparvovec.</description><identifier>ISSN: 2329-0501</identifier><identifier>EISSN: 2329-0501</identifier><identifier>DOI: 10.1016/j.omtm.2023.101117</identifier><language>eng</language><publisher>Elsevier Inc</publisher><subject>adeno-associated virus serotype 9 ; antibody titers ; gene therapy ; onasemnogene abeparvovec ; Original ; retrospective analysis ; seroprevalence ; spinal muscular atrophy</subject><ispartof>Molecular therapy. Methods & clinical development, 2023-12, Vol.31, p.101117-101117, Article 101117</ispartof><rights>2023 The Author(s)</rights><rights>2023 The Author(s) 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-e1fb19e07be34ce10687e3ba2241a49b29b80d4dbd0cfe7d86f0b8c0ad8d32a73</citedby><cites>FETCH-LOGICAL-c433t-e1fb19e07be34ce10687e3ba2241a49b29b80d4dbd0cfe7d86f0b8c0ad8d32a73</cites><orcidid>0000-0002-0086-9529</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562739/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562739/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,53790,53792</link.rule.ids></links><search><creatorcontrib>Day, John W.</creatorcontrib><creatorcontrib>Mendell, Jerry R.</creatorcontrib><creatorcontrib>Burghes, Arthur H.M.</creatorcontrib><creatorcontrib>van Olden, Rudolf W.</creatorcontrib><creatorcontrib>Adhikary, Rishi R.</creatorcontrib><creatorcontrib>Dilly, Keith W.</creatorcontrib><title>Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy</title><title>Molecular therapy. Methods & clinical development</title><description>Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implications. We conducted a retrospective study to describe the seroprevalence of anti-AAV9 binding antibodies for pediatric patients with SMA in the United States. At initial testing, 13.0% (115 of 882) of patients (mean [SD] age, 26.29 [33.66] weeks) had elevated AAV9-Ab titers. The prevalence of elevated titers decreased as age increased, with 18.2% (92 of 507) of patients ≤3 months old but only 1.1% (1 of 92) of patients ≥21 months old having elevated titers. This suggests transplacental maternal transfer of antibodies. No patterns of geographic variations in AAV9-Ab prevalence were confirmed. Elevated AAV9-Ab titers in children <6 weeks old decreased in all circumstances. Lower magnitudes of elevated titers declined more rapidly than greater magnitudes. Retesting was completed at the discretion of the treating clinician, so age at testing and time between tests varied. AAV9-Ab retesting should be considered when patients have elevated titers, and elevations at a young age are not a deterrent to eventual onasemnogene abeparvovec administration. Early disease-modifying treatment for SMA leads to optimal outcomes.
[Display omitted]
Day and colleagues describe the seroprevalence of anti-adeno-associated virus serotype 9 vector antibodies (AAV9-Ab), which has safety and efficacy considerations for spinal muscular atrophy (SMA) gene therapy with onasemnogene abeparvovec. Elevated AAV9-Ab concentrations were infrequent for children with SMA and decreased over time, allowing eventual administration of onasemnogene abeparvovec.</description><subject>adeno-associated virus serotype 9</subject><subject>antibody titers</subject><subject>gene therapy</subject><subject>onasemnogene abeparvovec</subject><subject>Original</subject><subject>retrospective analysis</subject><subject>seroprevalence</subject><subject>spinal muscular atrophy</subject><issn>2329-0501</issn><issn>2329-0501</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kU2LFDEQhhtRcFn3D3jK0UuP-ejp7oAgy-IXLHjQPYdKUu1k6E7aVHp0_r3dziJ6MZeEN_U-VdRbVS8F3wku2tfHXZrKtJNcqk0QontSXUkldc33XDz96_28uiE68vXojqu9vqp-3nqMqQai5AIU9OwU8kKMMKdynpFpBrEEm_z5tzZnPMGI0SEbUmYzlICxEAuRlQOyhxg2xpeyooj9COXAaA4RRjYt5JYRMoOyUg7nF9WzAUbCm8f7unp4_-7r3cf6_vOHT3e397VrlCo1isEKjbyzqBqHgrd9h8qClI2ARlupbc99463nbsDO9-3Abe84-N4rCZ26rt5euPNiJ_RunTbDaOYcJshnkyCYf39iOJhv6WQE37eyU3olvHok5PR9QSpmCuRwHCFiWsjIvmtb1Wgp11J5KXU5EWUc_vQR3GxZmaPZsjJbVuaS1Wp6czHhuoZTwGzIhW3DPmR0xfgU_mf_BcOUobY</recordid><startdate>20231214</startdate><enddate>20231214</enddate><creator>Day, John W.</creator><creator>Mendell, Jerry R.</creator><creator>Burghes, Arthur H.M.</creator><creator>van Olden, Rudolf W.</creator><creator>Adhikary, Rishi R.</creator><creator>Dilly, Keith W.</creator><general>Elsevier Inc</general><general>American Society of Gene & Cell Therapy</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0086-9529</orcidid></search><sort><creationdate>20231214</creationdate><title>Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy</title><author>Day, John W. ; Mendell, Jerry R. ; Burghes, Arthur H.M. ; van Olden, Rudolf W. ; Adhikary, Rishi R. ; Dilly, Keith W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-e1fb19e07be34ce10687e3ba2241a49b29b80d4dbd0cfe7d86f0b8c0ad8d32a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>adeno-associated virus serotype 9</topic><topic>antibody titers</topic><topic>gene therapy</topic><topic>onasemnogene abeparvovec</topic><topic>Original</topic><topic>retrospective analysis</topic><topic>seroprevalence</topic><topic>spinal muscular atrophy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Day, John W.</creatorcontrib><creatorcontrib>Mendell, Jerry R.</creatorcontrib><creatorcontrib>Burghes, Arthur H.M.</creatorcontrib><creatorcontrib>van Olden, Rudolf W.</creatorcontrib><creatorcontrib>Adhikary, Rishi R.</creatorcontrib><creatorcontrib>Dilly, Keith W.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular therapy. Methods & clinical development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Day, John W.</au><au>Mendell, Jerry R.</au><au>Burghes, Arthur H.M.</au><au>van Olden, Rudolf W.</au><au>Adhikary, Rishi R.</au><au>Dilly, Keith W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy</atitle><jtitle>Molecular therapy. Methods & clinical development</jtitle><date>2023-12-14</date><risdate>2023</risdate><volume>31</volume><spage>101117</spage><epage>101117</epage><pages>101117-101117</pages><artnum>101117</artnum><issn>2329-0501</issn><eissn>2329-0501</eissn><abstract>Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implications. We conducted a retrospective study to describe the seroprevalence of anti-AAV9 binding antibodies for pediatric patients with SMA in the United States. At initial testing, 13.0% (115 of 882) of patients (mean [SD] age, 26.29 [33.66] weeks) had elevated AAV9-Ab titers. The prevalence of elevated titers decreased as age increased, with 18.2% (92 of 507) of patients ≤3 months old but only 1.1% (1 of 92) of patients ≥21 months old having elevated titers. This suggests transplacental maternal transfer of antibodies. No patterns of geographic variations in AAV9-Ab prevalence were confirmed. Elevated AAV9-Ab titers in children <6 weeks old decreased in all circumstances. Lower magnitudes of elevated titers declined more rapidly than greater magnitudes. Retesting was completed at the discretion of the treating clinician, so age at testing and time between tests varied. AAV9-Ab retesting should be considered when patients have elevated titers, and elevations at a young age are not a deterrent to eventual onasemnogene abeparvovec administration. Early disease-modifying treatment for SMA leads to optimal outcomes.
[Display omitted]
Day and colleagues describe the seroprevalence of anti-adeno-associated virus serotype 9 vector antibodies (AAV9-Ab), which has safety and efficacy considerations for spinal muscular atrophy (SMA) gene therapy with onasemnogene abeparvovec. Elevated AAV9-Ab concentrations were infrequent for children with SMA and decreased over time, allowing eventual administration of onasemnogene abeparvovec.</abstract><pub>Elsevier Inc</pub><doi>10.1016/j.omtm.2023.101117</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0086-9529</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | adeno-associated virus serotype 9 antibody titers gene therapy onasemnogene abeparvovec Original retrospective analysis seroprevalence spinal muscular atrophy |
| title | Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy |
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