69
2.8.4 Phenylalanine Ammonia Lyase (PAL)
Phenylalanine hydroxylase (PAH) is an enzyme converting phenylalanine to tyrosine, and mutations in the PAH gene cause an autosomal recessive disorder called
phenylketonuria. Disease control is made possible by methods such as dietary treatment, amino acid supplementation, tetrahydropterin treatment, enzyme therapy, cell
therapy and gene therapy. Enzyme therapy is used to reduce the level of accumulated phenylalanine. Enzyme replacement therapy with phenylalanine hydroxylase
(PAH) or enzyme substitution with phenylalanine ammonia-lyase (PAL) is practised, of which treatment with PAL is advantageous. PAL can be immunogenic upon
injection and can be reduced by treating with PEG. PEG-PAL is less immunogenic,
and PEG-PAL formulations with more stability are also in development for oral
intake (Longo et al. 2014).
2.8.5 Dornase
Cystic fibrosis (CF) is an autosomal recessive disorder affecting exocrine glands.
Pulmonary disease is the major reason for mortality in CF patients. Airway obstruction leading to lung inflammation and bronchiectasis occurs in CF. Sputum becomes
thick due to dead neutrophils. Dornase alfa is a recombinant human deoxyribonuclease (DNase). It breaks down nucleic acid materials in the airways and thus
reduces the viscosity of sputum. Dornase alfa is commercially available as
Pulmozyme
®
and reduces airway obstruction by facilitating mucus clearance in
lungs (Jones and Wallis 2010).
2.8.6 Rasburicase
Tumour lysis syndrome (TLS) occurs within 72 h after initiation of cancer therapy
and is characterized by release of tumour cell contents in the circulatory system
leading to hyperuricemia, metabolic acidosis, etc. TLS can be life-threatening and
oliguria (acute kidney injury) may occur due to crystallization of uric acid and calcium phosphate in the renal tubules. Hyperuricemia can be overcome by degrading
uric acid by urate oxidase. Rasburicase is a recombinant urate oxidase from
Aspergillus flavus and is expressed in Saccharomyces cerevisiae (Bayol et al. 2002).
The US Food and Drug Administration (FDA) approved rasburicase in 2009 and it
is commercially available as Elitek/Fasturtec
®
. It is effective in TLS management
and the preferred choice in paediatric patients with acute leukaemia and
lymphoma.
2 Therapeutic Enzymes
2.8.4 Phenylalanine Ammonia Lyase (PAL)
Phenylalanine hydroxylase (PAH) is an enzyme converting phenylalanine to tyrosine, and mutations in the PAH gene cause an autosomal recessive disorder called
phenylketonuria. Disease control is made possible by methods such as dietary treatment, amino acid supplementation, tetrahydropterin treatment, enzyme therapy, cell
therapy and gene therapy. Enzyme therapy is used to reduce the level of accumulated phenylalanine. Enzyme replacement therapy with phenylalanine hydroxylase
(PAH) or enzyme substitution with phenylalanine ammonia-lyase (PAL) is practised, of which treatment with PAL is advantageous. PAL can be immunogenic upon
injection and can be reduced by treating with PEG. PEG-PAL is less immunogenic,
and PEG-PAL formulations with more stability are also in development for oral
intake (Longo et al. 2014).
2.8.5 Dornase
Cystic fibrosis (CF) is an autosomal recessive disorder affecting exocrine glands.
Pulmonary disease is the major reason for mortality in CF patients. Airway obstruction leading to lung inflammation and bronchiectasis occurs in CF. Sputum becomes
thick due to dead neutrophils. Dornase alfa is a recombinant human deoxyribonuclease (DNase). It breaks down nucleic acid materials in the airways and thus
reduces the viscosity of sputum. Dornase alfa is commercially available as
Pulmozyme
®
and reduces airway obstruction by facilitating mucus clearance in
lungs (Jones and Wallis 2010).
2.8.6 Rasburicase
Tumour lysis syndrome (TLS) occurs within 72 h after initiation of cancer therapy
and is characterized by release of tumour cell contents in the circulatory system
leading to hyperuricemia, metabolic acidosis, etc. TLS can be life-threatening and
oliguria (acute kidney injury) may occur due to crystallization of uric acid and calcium phosphate in the renal tubules. Hyperuricemia can be overcome by degrading
uric acid by urate oxidase. Rasburicase is a recombinant urate oxidase from
Aspergillus flavus and is expressed in Saccharomyces cerevisiae (Bayol et al. 2002).
The US Food and Drug Administration (FDA) approved rasburicase in 2009 and it
is commercially available as Elitek/Fasturtec
®
. It is effective in TLS management
and the preferred choice in paediatric patients with acute leukaemia and
lymphoma.
2 Therapeutic Enzymes