Hepatobiliary disease in XLMTM. A common comorbidity with potential impact on treatment strategies
Abstract BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from pathogenic variants in the MTM1 gene. Affected male subjects typically present with severe hypotonia and respiratory distress at birth and they often require intensive supportive care. Long-term survivors are often non-ambulant, ventilator and feeding tube–dependent and they generally show additional organ manifestations, indicating that myotubularin does play a vital role in tissues other than muscle. For XLMTM several therapeutic strategies are under investigation.A recent clinical trial delivering the MTM1 gene using a recombinant AAV8 vector to XLMTM patients showed encouraging results in term of efficacy, but some concerns about safety arised due to three fatal events related to hepatotoxicity in boys that were exposed to the higher dose.RESULTS: We report prospective and retrospective clinical data of 12 XLMTM patients collected over a period of up to 10 years. In particular, we carried out a thorough review of the data about incidence and the course of hepatobiliary disease in our case series.CONCLUSIONS: We demonstrate that hepatobiliary disease represents a common comorbidity of XLMTM that seems irrespective to age and diseases severity. We recommend to carefully explore and monitor the hepatobiliary function in XLMTM patients. We believe that a better understanding of the pathogenic mechanisms that induce hepatobiliary damage is essential to understand the fatal events that may occur in the gene therapy program..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 29. Juli Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
D'Amico, Adele [VerfasserIn] |
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| doi: |
10.21203/rs.3.rs-757577/v1 |
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| PPN (Katalog-ID): |
XRA034497579 |
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| 520 | |a Abstract BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from pathogenic variants in the MTM1 gene. Affected male subjects typically present with severe hypotonia and respiratory distress at birth and they often require intensive supportive care. Long-term survivors are often non-ambulant, ventilator and feeding tube–dependent and they generally show additional organ manifestations, indicating that myotubularin does play a vital role in tissues other than muscle. For XLMTM several therapeutic strategies are under investigation.A recent clinical trial delivering the MTM1 gene using a recombinant AAV8 vector to XLMTM patients showed encouraging results in term of efficacy, but some concerns about safety arised due to three fatal events related to hepatotoxicity in boys that were exposed to the higher dose.RESULTS: We report prospective and retrospective clinical data of 12 XLMTM patients collected over a period of up to 10 years. In particular, we carried out a thorough review of the data about incidence and the course of hepatobiliary disease in our case series.CONCLUSIONS: We demonstrate that hepatobiliary disease represents a common comorbidity of XLMTM that seems irrespective to age and diseases severity. We recommend to carefully explore and monitor the hepatobiliary function in XLMTM patients. We believe that a better understanding of the pathogenic mechanisms that induce hepatobiliary damage is essential to understand the fatal events that may occur in the gene therapy program. | ||
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| 700 | 1 | |a Fattori, Fabiana |e verfasserin |4 aut | |
| 700 | 1 | |a Tosi, Michele |e verfasserin |4 aut | |
| 700 | 1 | |a Bosco, Luca |e verfasserin |4 aut | |
| 700 | 1 | |a Testa, Maria Beatrice Chiarini |e verfasserin |4 aut | |
| 700 | 1 | |a Paglietti, Giovanna |e verfasserin |4 aut | |
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