How we choose factor VIII to treat hemophilia

Mannucci, Pier Mannuccio; Mancuso, Maria Elisa; Santagostino, Elena

doi:10.1182/blood-2012-01-394411

Cited by 67 publications

(54 citation statements)

References 59 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…31,32 To date, there is no conclusive evidence on distinct rates of inhibitor formation comparing recombinant BDD or full-length FVIII. 8 Moreover, the B-domain sequence is the most polymorphic of all the FVIII domains. 10,33 Together these findings suggest that minimal modifications in B-domain sequence, as reported here, may not increase FVIII immunogenicity.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype

Siner

Iacobelli

Sabatino

et al. 2013

Blood

View full text Add to dashboard Cite

• The novel FVIII variant (FVIII-RH) has enhanced stability and procoagulant activity in both in vitro and in vivo models.• FVIII-RH is efficacious and safe; thus, it is an attractive molecule for protein replacement and as a transgene in gene-therapy strategies.Recombinant canine B-domain deleted (BDD) factor VIII (FVIII) is predominantly expressed as a single-chain protein and exhibits greater stability after activation compared with human FVIII-BDD. We generated a novel BDD-FVIII variant (FVIII-RH) with an amino acid change at the furin cleavage site within the B domain (position R1645H) that mimics the canine sequence (HHQR vs human RHQR). Compared with human FVIII-BDD, expression of FVIII-RH protein revealed a 2.5-fold increase in the single-chain form. Notably, FVIII-RH exhibited a twofold increase in biological activity compared with FVIII-BDD, likely due to its slower dissociation of the A2-domain upon thrombin activation. Injection of FVIII-RH protein in hemophilia A (HA) mice resulted in more efficacious hemostasis following vascular injury in both the macro-and microcirculation. These findings were successfully translated to adeno-associated viral (AAV)-based liver gene transfer in HA mice. Expression of circulating FVIII-RH was approximately twofold higher compared with AAV-FVIII-BDD-injected mice. Moreover, FVIII-RH exhibits superior procoagulant effects compared with FVIII-BDD following a series of hemostatic challenges. Notably, the immunogenicity of FVIII-RH did not differ from FVIII-BDD. Thus, FVIII-RH is an attractive bioengineered molecule for improving efficacy without increased immunogenicity and may be suitable for both protein-and genebased strategies for HA. (Blood. 2013;121(21):4396-4403)

show abstract

Section: Discussionmentioning

confidence: 99%

“…6,7 Recombinant FVIII-BDD has been efficacious and safe in the clinical management of HA patients over the last several decades. 8 Recently, we generated a canine version of the BDD-FVIII protein. 9 We uncovered that, in comparison with human FVIII, the canine protein exhibits enhanced biological activity.…”

Section: Introductionmentioning

confidence: 99%

Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype

Siner

Iacobelli

Sabatino

et al. 2013

Blood

View full text Add to dashboard Cite

show abstract

“…Medical and scientific advisory council, MASAC) ameriške nacionalne fundacije za hemofilijo (angl. National Haemophilia Foundation, NHF) je leta 2014 priporočil, naj bodo rekombinantni faktorji na voljo vsem bolnikom s hemofilijo, ki bi imeli od tega koristi, in naj se odstranijo vse ovire pri prehajanju s plazemskih na rekombinantne koagulacijske faktorje (14,15).…”

Section: Koagulacijski Faktorjiunclassified

Nacionalna priporočila za obravnavo bolnikov s hemofilijo

et al. 2017

View full text Add to dashboard Cite

The document presents recommendations for the comprehensive treatment of patients with haemophilia in Slovenia. It enables health workers at all three levels of health care to become well-acquainted with all the possible aspects of treatment based on the best practices of major centres worldwide, and on the studies and experience of health professionals at the National Haemophilia Centre, University Medical Center Ljubljana. The document contains definitions, treatment algorithms and lists of medications with their characteristics and appropriate dosages. It specifically defines indications for the exclusive competence of the tertiary level in Ljubljana due to the actual availability of teams and laboratory options. It also contains an extensive list of the literature on haemophilia.

show abstract

“…Nowadays, quite a lot of hemophilia A patients are treated with a periodical injection of FVIII, which has become a short but essential clinical drug. 4 Currently, the production of FVIII is acquired mainly through two approaches: extracting from fresh plasma 5 and gene recombination technique. However, the¯rst method, including the steps of separation, puri¯cation, viral inactivation/removal and freeze-drying, is the main procedure to get the FVIII products in China and many other countries.…”

Section: Introductionmentioning

confidence: 99%

Application of near infrared spectroscopy in monitoring the moisture content in freeze-drying process of human coagulation factor VIII

Wang

Jiang

et al. 2015

J. Innov. Opt. Health Sci.

View full text Add to dashboard Cite

As an important process analysis tool, near infrared spectroscopy (NIRS) has been widely used in process monitoring. In the present work, the feasibility of NIRS for monitoring the moisture content of human coagulation factor VIII (FVIII) in freeze-drying process was investigated. A partial least squares regression (PLS-R) model for moisture content determination was built with 88 samples. Di®erent pre-processing methods were explored, and the best method found was standard normal variate (SNV) transformation combined with 1st derivation with SavitzkyGolay (SG) 15 point smoothing. Then, four di®erent variable selection methods, including uninformative variable elimination (UVE), interval partial least squares regression (iPLS), competitive adaptive reweighted sampling (CARS) and manual method, were compared for eliminating irrelevant variables, and iPLS was chosen as the best variable selection method. The correlation coe±cient (R), correlation coe±cient of calibration set (R cal ), correlation coe±cient of validation set (R val ), root mean square errors of cross-validation (RMSECV) and root mean square errors of prediction (RMSEP) of PLS model were 0.9284, 0.9463, 0.8890, 0.4986% and 0.4514%, respectively. The results showed that the model for moisture content determination has a wide range, good linearity, accuracy and precision. The developed approach was demonstrated to be a potential for monitoring the moisture content of FVIII in freeze-drying process.

show abstract

How we choose factor VIII to treat hemophilia

Cited by 67 publications

References 59 publications

Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype

Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype

Nacionalna priporočila za obravnavo bolnikov s hemofilijo

Application of near infrared spectroscopy in monitoring the moisture content in freeze-drying process of human coagulation factor VIII

Contact Info

Product

Resources

About