Ethical and Regulatory Considerations of Placental Therapeutics
Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy a...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
David, Anna L. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Clinical therapeutics - Amsterdam [u.a.] : Elsevier Science, 1995, 43 |
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| Übergeordnetes Werk: |
volume:43 |
| DOI / URN: |
10.1016/j.clinthera.2021.01.003 |
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| Katalog-ID: |
ELV005787173 |
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| 245 | 1 | 0 | |a Ethical and Regulatory Considerations of Placental Therapeutics |
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| 520 | |a Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.Methods: This article reviews the literature on ethical and regulatory considerations for placental therapeutics.Findings: Proposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.Implications: Developing placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible. | ||
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| 650 | 4 | |a ethics | |
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10.1016/j.clinthera.2021.01.003 doi (DE-627)ELV005787173 (ELSEVIER)S0149-2918(21)00005-9 DE-627 ger DE-627 rda eng 610 DE-600 PHARM DE-84 fid 15,3 ssgn 44.40 bkl 44.52 bkl David, Anna L. verfasserin aut Ethical and Regulatory Considerations of Placental Therapeutics 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.Methods: This article reviews the literature on ethical and regulatory considerations for placental therapeutics.Findings: Proposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.Implications: Developing placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible. adverse events ethics fetus gene therapy mother Enthalten in Clinical therapeutics Amsterdam [u.a.] : Elsevier Science, 1995 43 Online-Ressource (DE-627)320646033 (DE-600)2025417-9 (DE-576)261874578 1879-114X nnns volume:43 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.40 Pharmazie Pharmazeutika 44.52 Therapie Medizin AR 43 |
| spelling |
10.1016/j.clinthera.2021.01.003 doi (DE-627)ELV005787173 (ELSEVIER)S0149-2918(21)00005-9 DE-627 ger DE-627 rda eng 610 DE-600 PHARM DE-84 fid 15,3 ssgn 44.40 bkl 44.52 bkl David, Anna L. verfasserin aut Ethical and Regulatory Considerations of Placental Therapeutics 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.Methods: This article reviews the literature on ethical and regulatory considerations for placental therapeutics.Findings: Proposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.Implications: Developing placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible. adverse events ethics fetus gene therapy mother Enthalten in Clinical therapeutics Amsterdam [u.a.] : Elsevier Science, 1995 43 Online-Ressource (DE-627)320646033 (DE-600)2025417-9 (DE-576)261874578 1879-114X nnns volume:43 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.40 Pharmazie Pharmazeutika 44.52 Therapie Medizin AR 43 |
| allfields_unstemmed |
10.1016/j.clinthera.2021.01.003 doi (DE-627)ELV005787173 (ELSEVIER)S0149-2918(21)00005-9 DE-627 ger DE-627 rda eng 610 DE-600 PHARM DE-84 fid 15,3 ssgn 44.40 bkl 44.52 bkl David, Anna L. verfasserin aut Ethical and Regulatory Considerations of Placental Therapeutics 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.Methods: This article reviews the literature on ethical and regulatory considerations for placental therapeutics.Findings: Proposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.Implications: Developing placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible. adverse events ethics fetus gene therapy mother Enthalten in Clinical therapeutics Amsterdam [u.a.] : Elsevier Science, 1995 43 Online-Ressource (DE-627)320646033 (DE-600)2025417-9 (DE-576)261874578 1879-114X nnns volume:43 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.40 Pharmazie Pharmazeutika 44.52 Therapie Medizin AR 43 |
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10.1016/j.clinthera.2021.01.003 doi (DE-627)ELV005787173 (ELSEVIER)S0149-2918(21)00005-9 DE-627 ger DE-627 rda eng 610 DE-600 PHARM DE-84 fid 15,3 ssgn 44.40 bkl 44.52 bkl David, Anna L. verfasserin aut Ethical and Regulatory Considerations of Placental Therapeutics 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.Methods: This article reviews the literature on ethical and regulatory considerations for placental therapeutics.Findings: Proposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.Implications: Developing placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible. adverse events ethics fetus gene therapy mother Enthalten in Clinical therapeutics Amsterdam [u.a.] : Elsevier Science, 1995 43 Online-Ressource (DE-627)320646033 (DE-600)2025417-9 (DE-576)261874578 1879-114X nnns volume:43 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.40 Pharmazie Pharmazeutika 44.52 Therapie Medizin AR 43 |
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10.1016/j.clinthera.2021.01.003 doi (DE-627)ELV005787173 (ELSEVIER)S0149-2918(21)00005-9 DE-627 ger DE-627 rda eng 610 DE-600 PHARM DE-84 fid 15,3 ssgn 44.40 bkl 44.52 bkl David, Anna L. verfasserin aut Ethical and Regulatory Considerations of Placental Therapeutics 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.Methods: This article reviews the literature on ethical and regulatory considerations for placental therapeutics.Findings: Proposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.Implications: Developing placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible. adverse events ethics fetus gene therapy mother Enthalten in Clinical therapeutics Amsterdam [u.a.] : Elsevier Science, 1995 43 Online-Ressource (DE-627)320646033 (DE-600)2025417-9 (DE-576)261874578 1879-114X nnns volume:43 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.40 Pharmazie Pharmazeutika 44.52 Therapie Medizin AR 43 |
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ethical and regulatory considerations of placental therapeutics |
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Ethical and Regulatory Considerations of Placental Therapeutics |
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Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.Methods: This article reviews the literature on ethical and regulatory considerations for placental therapeutics.Findings: Proposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.Implications: Developing placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible. |
| abstractGer |
Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.Methods: This article reviews the literature on ethical and regulatory considerations for placental therapeutics.Findings: Proposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.Implications: Developing placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible. |
| abstract_unstemmed |
Purpose: Placental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.Methods: This article reviews the literature on ethical and regulatory considerations for placental therapeutics.Findings: Proposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.Implications: Developing placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible. |
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|
| score |
7.399722 |