Adeno-Associated Virus Gene Therapy for Hemophilia

Samelson-Jones, Ben; George, Lindsey A.

doi:10.1146/annurev-med-043021-033013

Cited by 53 publications

(65 citation statements)

References 89 publications

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“…Importantly, however, the same animals were followed-up for 10 years without evidence of tumorigenesis; nonetheless, this study provides the first large-animal data to highlight the risk of AAV-mediated integration. 58 …”

Section: Requirements For Implementing Gene Therapymentioning

confidence: 99%

“…In the short-term, haemophilia treatment centres will require additional resources to coordinate care and follow-up of gene therapy recipients. 58 Both physicians and nurses will become heavily involved in patient education; additional investment in psychosocial support may be required, as will be new processes for ordering, storing, and handling gene therapy products, with possible repercussion on the pharmacists. During the first months following gene therapy, the liver health must be closely monitored, with additional workload on hepatologists.…”

Section: Haemophilia Care Centresmentioning

confidence: 99%

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How to translate and implement the current science of gene therapy into haemophilia care?

Hermans

Gruel

Frenzel

et al. 2023

Therapeutic Advances in Hematology

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Gene-based therapy opens an entirely new paradigm in managing people with haemophilia (PWH), offering them the possibility of a functional cure by enabling continuous expression of factor VIII (FVIII) or factor IX (FIX) after transfer of a functional gene designed to replace the PWH’s own defective gene. In recent years, significant advances in gene therapy have been made, resulting in clotting factor activity attaining near-normal levels, as reflected by ‘zero bleeding rates’ in previously severely inflicted patients following a single administration of adeno-associated viral (AAV) vectors. While this new approach represents a major advancement, there are still several issues that must be resolved before applying this technology in clinical practice. First, awareness, communication, and education about the therapeutic potential and modalities of gene therapy must be further strengthened. To this end, objective, unbiased, transparent, and regularly updated information must be shared, in an appropriate way and understandable language with the support of patients’ organizations. Second, healthcare providers should adopt a patient-centred approach, as the ‘one size fits all’ approach is inappropriate when considering gene therapy. Instead, a holistic patient view taking into account their physical and mental dimensions, along with unexpressed expectations and preferences, is mandatory. Third, the consent procedure must be improved, ensuring that patients’ interests are maximally protected. Finally, gene therapy is likely to be first delivered in a few centres, with the highest expertise and experience in this domain. Thus, patients should be managed based on a hub-and-spoke model, taking into account that the key to gene therapy’s success lies in an optimal communication and collaboration both within and between haemophilia centres sharing their experiences in the frame of international registries. This review describes recent progress and explains outstanding hurdles that must be tackled to ease the implementation of this paradigm-changing new therapy.

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Section: Requirements For Implementing Gene Therapymentioning

confidence: 99%

Section: Haemophilia Care Centresmentioning

confidence: 99%

How to translate and implement the current science of gene therapy into haemophilia care?

Hermans

Gruel

Frenzel

et al. 2023

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

show abstract

“…This raises concerns about the durability and safety of AAV-based liver-specific gene therapy. Currently, several AAV-based gene transfer strategies have been modified and clinical trials have been initiated, which could offer hope to improve the durability and safety of this therapy for patients with hemophilia ( 140 – 143 ).…”

Section: Novel Strategies For Eradicating Inhibitors or Immune Tolera...mentioning

confidence: 99%

Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications

et al. 2022

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The development of coagulation factor VIII (FVIII) inhibitory antibodies is a serious complication in hemophilia A (HA) patients after FVIII replacement therapy. Inhibitors render regular prophylaxis ineffective and increase the risk of morbidity and mortality. Immune tolerance induction (ITI) regimens have become the only clinically proven therapy for eradicating these inhibitors. However, this is a lengthy and costly strategy. For HA patients with high titer inhibitors, bypassing or new hemostatic agents must be used in clinical prophylaxis due to the ineffective ITI regimens. Since multiple genetic and environmental factors are involved in the pathogenesis of inhibitor generation, understanding the mechanisms by which inhibitors develop could help identify critical targets that can be exploited to prevent or eradicate inhibitors. In this review, we provide a comprehensive overview of the recent advances related to mechanistic insights into anti-FVIII antibody development and discuss novel therapeutic approaches for HA patients with inhibitors.

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“…[22][23][24][25][26][27][28] Gene therapy clinical trials for adults with haemophilia were initiated three decades ago and have demonstrated cautiously optimistic results. 29 Still, no human clinical trials have been approved for prenatal cell and/or gene therapy for haemophilia, despite its potential for providing a curative solution for this population.…”

Section: Introductionmentioning

confidence: 99%

Acceptability of prenatal diagnosis and prenatal treatment of haemophilia using cell and gene therapies within US haemophilia community

Pham

Thomson

Schaible³

et al. 2023

Haemophilia

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Background The overall burden of disease in persons with haemophilia continues to be high despite the latest advancements in therapeutics. Clinical trials testing prenatal treatments for several genetic disorders are underway or are recruiting subjects, attesting to the much‐needed change in paradigm of how patients with monogenic disorders can be treated. Here we investigate the overall attitude towards prenatal diagnosis, preferences on types of prenatal therapies for haemophilia, the level of 'acceptable' risk tolerated, and which social and moral pressures or disease personal experiences may predict willingness of individuals to consider foetal therapy in a future pregnancy. Results A multidisciplinary team designed the survey, and the study was carried out using REDCap, and publicized through the National Haemophilia Foundation. Subjects ≥18 years of age were eligible to participate in the study. We assessed participants’ attitudes towards prenatal therapy and their level of 'acceptable' risk towards the procedure and therapy. The survey was completed by 67 adults, the majority females. Respondents were willing to undergo prenatal diagnosis, and their main concerns related to the well‐being of the pregnant woman and the foetus regarding lasting therapeutic efficacy, side effects of the therapy, and procedural risks, but they were likely to accept a wide range of prenatal therapeutic options, particularly if the foetal therapy proved to be long‐lasting and safe. Conclusions These data demonstrate the willingness of persons with haemophilia, and the haemophilia community, to explore new treatment options beyond the currently offered approaches.

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Adeno-Associated Virus Gene Therapy for Hemophilia

Cited by 53 publications

References 89 publications

How to translate and implement the current science of gene therapy into haemophilia care?

How to translate and implement the current science of gene therapy into haemophilia care?

Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications

Acceptability of prenatal diagnosis and prenatal treatment of haemophilia using cell and gene therapies within US haemophilia community

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