Advances in gene therapy for hemophilia

Robles-Rodríguez, Olivia A; Perez‐Trujillo, José Juan; Villanueva-Olivo, Arnulfo; Villarreal‐Martínez, Laura; Marfil-Rivera, Luis Javier; Rodríguez-Rocha, Humberto; García-García, Aracely; Saucedo‐Cárdenas, Odila; Loera‐Arias, María de Jesús; Oca‐Luna, Roberto Montes de

doi:10.1007/s12038-020-00057-y

Cited by 4 publications

(6 citation statements)

References 45 publications

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“…17,32 While viral vectors such as AAV, lentivirus, and retrovirus may cause immune or inflammatory reactions, they are widely used in gene therapy because they are very effective in delivering the functional gene into the cell. 35,46 For example, Luxturna and Zolgensma, the FDA-approved gene therapies for genetic diseases, are both AAVbased. 48 Compared with viral vectors, the therapy with non-viral vectors such as liposomes, electroporation, plasmids, peptides, and mRNA are less likely to cause immune and inflammatory reactions, activate oncogenes, or generate off-target effects, and they are also low cost.…”

Section: Discussionmentioning

confidence: 99%

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Future of genetic therapies for rare genetic diseases: what to expect for the next 15 years?

Braga

Filho

Mota

2022

Therapeutic Advances in Rare Disease

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Introduction: Rare genetic diseases affect millions of people worldwide. Most of them are caused by defective genes that impair quality of life and can lead to premature death. As genetic therapies aim to fix or replace defective genes, they are considered the most promising treatment for rare genetic diseases. Yet, as these therapies are still under development, it is still unclear whether they will be successful in treating these diseases. This study aims to address this gap by assessing researchers’ opinions on the future of genetic therapies for the treatment of rare genetic diseases. Methods: We conducted a global cross-sectional web-based survey of researchers who recently authored peer-reviewed articles related to rare genetic diseases. Results: We assessed the opinions of 1430 researchers with high and good knowledge about genetic therapies for the treatment of rare genetic diseases. Overall, the respondents believed that genetic therapies would be the standard of care for rare genetic diseases before 2036, leading to cures after this period. CRISPR-Cas9 was considered the most likely approach to fixing or replacing defective genes in the next 15 years. The respondents with good knowledge believed that genetic therapies would only have long-lasting effects after 2036, while those with high knowledge were divided on this issue. The respondents with good knowledge on the subject believed that non-viral vectors are more likely to be successful in fixing or replacing defective genes in the next 15 years, while most of the respondents with high knowledge believed viral vectors would be more successful. Conclusion: Overall, the researchers who participated in this study expect that in the future genetic therapies will greatly benefit the treatment of patients with rare genetic diseases. Plain Language Summary A global survey of researchers on the future of genetic therapies for rare genetic diseases Rare genetic diseases are caused by defective genes that result from one or more mutations in the genome. Today, the therapeutic options for these diseases are limited, and there are approved treatments for about 5% of them. In the future, genetic therapies (a group of techniques developed to correct defective genes) are expected to revolutionize the treatment of rare genetic diseases. Although promising, most of these therapies are currently under development and have a long way to go before their efficacy and safety can be proved. The uncertainty surrounding this topic therefore means the success of genetic therapies in treating or curing rare genetic diseases is not yet assured. To address this knowledge gap, we surveyed 1430 researchers working in rare genetic diseases about the future of genetic therapies for the treatment of these diseases over the next 15 years. Most of them expected gene therapies to be the standard of care for rare genetic diseases before 2036 and to be able to cure them after this date. CRISPR-Cas9 was felt to be the gene editing approach that was most likely to succeed in fixing or replacing defective genes in the next 15 years. The respondents with high knowledge about gene therapies for the treatment of rare diseases believed gene therapies would have long-lasting effects before 2036, while those with good knowledge expected this to be the case only after 2036. The former believed in viral vectors and the latter in non-viral vectors to fix or replace defective genes in the next 15 years.

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Section: Discussionmentioning

confidence: 99%

“…Then, we downloaded the full articles and, after reading them, selected the 66 references used in the literature review that led to the survey questionnaire. 2 , 5 – 19 , 22 , 25 , 32 , 34 – 37 , 39 – 41 , 46 – 85 …”

Section: Methodsmentioning

confidence: 99%

Future of genetic therapies for rare genetic diseases: what to expect for the next 15 years?

Braga

Filho

Mota

2022

Therapeutic Advances in Rare Disease

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“…Student uncoupled t test was performed ( P < .0001) to determine the level of significance as described. 34 (B-D) Effect of PS antibody on thrombin generation in patient plasmas (patients 1-11). Results are grouped according to severity of hemophilia, with panels B-D representing severe, mild, and moderate hemophilia, respectively.…”

Section: Resultsmentioning

confidence: 99%

Protein S antibody as an adjunct therapy for hemophilia B

Wilson,

Pierre,

Paysse

et al. 2024

Blood Advances

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Hemophilia B (HB) is caused by an inherited deficiency of plasma coagulation Factor IX (FIX). Approximately sixty percent of pediatric patients with HB possess the severe form of FIX deficiency (<1% FIX activity). Treatment typically requires replacement therapy by the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant Protein S (PS) inhibits activated FIX (FIXa). Protein S ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX, and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercial and pediatric patient HB plasmas. We included eleven pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Further, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.

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“…FIX with higher purity, better safety and better patient compliance will be developed for the treatment of haemophilia B. Of course, gene therapy will increasingly become a new trend [26]. As a key factor in the coagulation pathway, FIX will also play a greater role in the treatment of coagulation disorders caused by the lack of other factors.…”

Section: Discussionmentioning

confidence: 99%

Human coagulation factor IX: a systematic review of its characteristics

Yin¹,

Liu²

2021

Blood Coagulation &Amp; Fibrinolysis

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Human coagulation factor IX (FIX) is a vitamin K dependent glycoprotein. It is used in therapy of factor IX deficiency, known as haemophilia B. This article explained the coagulation process involved in FIX and the principle of haemophilia B caused by its absence. We searched and aligned the sequence information of IX in the NCBI's EST database to predict its structure and understand the molecular biological basis of its function. Further, by sorting out the development history of FIX, we summarized the general process of its isolation and purification. Finally, the clinical indications and complications of FIX were overviewed. Through a comprehensive description of the characteristics of FIX, we hope to give readers a clear understanding and put forward our views on the future development of the product. Blood Coagul Fibrinolysis

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Advances in gene therapy for hemophilia

Cited by 4 publications

References 45 publications

Future of genetic therapies for rare genetic diseases: what to expect for the next 15 years?

Future of genetic therapies for rare genetic diseases: what to expect for the next 15 years?

Protein S antibody as an adjunct therapy for hemophilia B

Human coagulation factor IX: a systematic review of its characteristics

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