64
(I2S) responsible for breakdown of heparan sulphate and dermatan sulphate triggering subsequent accumulation of them within the lysosomes (Noh and Lee 2014).
Idursulphase (recombinant form of human I2S) has been approved for ERT against
MPS II and has been available since 2006. MPS VI, also known as MaroteauxLamy syndrome, is characterized by a deficiency of arylsulphatase B (N-acetyl
galactosamine 4-sulphatase) causing lysosomal accumulation of dermatan sulphate
and chondroitin sulphate. Galsulphase (recombinant human arylsulphatase B) has
been approved and has been available since 2005 for treatment. ERTs against other
MPSs are in development and yet to be approved. ERT is a lifelong treatment leading to improvement in locomotion and respiration and eventually improving the
quality of life of patients suffering from MPSs (Table 2.3).
2.7
Treatment of Bleeding Disorders
Haemophilia is an inherited excessive bleeding disorder. It has two types, namely
haemophilia A, characterized by insufficiency of clotting factor VIII, and haemophilia B, characterized by insufficiency of clotting factor IX. Haemophilia patients
are at high risk during injury and surgery. Mostsurgical procedures are not recommended to them due to post-operative bleeding complications. Intravenous infusion
of corresponding clotting factor (FVIII/FIX) is the remedy for this.
2.7.1 Recombinant Factor VIII
As mentioned earlier, haemophilia A is characterized by deficiency of factor
VIII. Plasma-derived coagulation factor VIII (FVIII) was initially used for replacement therapy of the disease, which was later replaced by recombinant factor VIII
with the advancement of recombinant DNA techniques. A fusion protein was developed by combining a single molecule of recombinant FVIII (rFVIII) and Fc domain
of human IgG1 expressed in human embryonic kidney (HEK) 293H cells. Compared
to rFVIII, the fusion protein (rFVIIIFc) has increased efficacy, prolonged half-life,
etc. (Peters et al. 2013). rFVIIIFc is commercially available as efraloctocog alfa for
treatment of haemophilia A. Unfortunately, some patients develop alloantibodies
against FVIII, which creates problems in the treatment of patients with antibodies
as inhibitors.
2.7.2 Recombinant Factor IX
Haemophilia B treatment involves infusion factor IX (FIX) concentrates. They can
be given on demand during an emergency or prophylactically to prevent bleeding
(given in minimum dose). Factor IX or Christmas factor is a serine protease, and
initially plasma-derived FIX concentrates were given for treatment and later
S.S. Kumar and S. Abdulhameed
(I2S) responsible for breakdown of heparan sulphate and dermatan sulphate triggering subsequent accumulation of them within the lysosomes (Noh and Lee 2014).
Idursulphase (recombinant form of human I2S) has been approved for ERT against
MPS II and has been available since 2006. MPS VI, also known as MaroteauxLamy syndrome, is characterized by a deficiency of arylsulphatase B (N-acetyl
galactosamine 4-sulphatase) causing lysosomal accumulation of dermatan sulphate
and chondroitin sulphate. Galsulphase (recombinant human arylsulphatase B) has
been approved and has been available since 2005 for treatment. ERTs against other
MPSs are in development and yet to be approved. ERT is a lifelong treatment leading to improvement in locomotion and respiration and eventually improving the
quality of life of patients suffering from MPSs (Table 2.3).
2.7
Treatment of Bleeding Disorders
Haemophilia is an inherited excessive bleeding disorder. It has two types, namely
haemophilia A, characterized by insufficiency of clotting factor VIII, and haemophilia B, characterized by insufficiency of clotting factor IX. Haemophilia patients
are at high risk during injury and surgery. Mostsurgical procedures are not recommended to them due to post-operative bleeding complications. Intravenous infusion
of corresponding clotting factor (FVIII/FIX) is the remedy for this.
2.7.1 Recombinant Factor VIII
As mentioned earlier, haemophilia A is characterized by deficiency of factor
VIII. Plasma-derived coagulation factor VIII (FVIII) was initially used for replacement therapy of the disease, which was later replaced by recombinant factor VIII
with the advancement of recombinant DNA techniques. A fusion protein was developed by combining a single molecule of recombinant FVIII (rFVIII) and Fc domain
of human IgG1 expressed in human embryonic kidney (HEK) 293H cells. Compared
to rFVIII, the fusion protein (rFVIIIFc) has increased efficacy, prolonged half-life,
etc. (Peters et al. 2013). rFVIIIFc is commercially available as efraloctocog alfa for
treatment of haemophilia A. Unfortunately, some patients develop alloantibodies
against FVIII, which creates problems in the treatment of patients with antibodies
as inhibitors.
2.7.2 Recombinant Factor IX
Haemophilia B treatment involves infusion factor IX (FIX) concentrates. They can
be given on demand during an emergency or prophylactically to prevent bleeding
(given in minimum dose). Factor IX or Christmas factor is a serine protease, and
initially plasma-derived FIX concentrates were given for treatment and later
S.S. Kumar and S. Abdulhameed