Therapeutic application of enzymes

Therapeutic Applications of Enzymes

Learning Goals

• Understand that a deficiency or reduced activity of enzymes can cause disease (e.g., GSD Type II, hyperlipidaemia).
• Understand how enzymes can be used as therapeutic agents, either directly or in gene therapy-based procedures.
• Understand how enzymes can be used in many detection methods (i.e., bioluminescence, chemiluminescence, Western blot) and also in a variety of industrial/commercial/pharmaceutical processes (e.g., drug manufacturing).
• Understand that enzymes can be engineered to improve their efficiency.

Enzyme Deficiency and Disease

• Deficiency or reduced activity of enzymes can cause disease.
• Glycogen Storage Diseases (GSD): These are metabolic disorders involving enzymes that regulate glycogen metabolism.
  • GSD Type II (Pompe's disease): Caused by a deficiency of lysosomal \alpha -glucosidase, leading to the accumulation of glycogen in lysosomes.
    • This accumulation results in muscle weakness and nerve damage, potentially leading to heart failure.
    • Treatment involves administering myozyme, which replaces the defective enzyme.

Enzymes as Therapeutic Agents

• Enzymes can be used as therapeutic agents to treat disease processes.
• Stroke:
  • Exogenous enzymes are applied to break up blood clots.
  • Examples of enzymes used include streptokinase, tissue plasminogen activator (t-PA), and urokinase.
• Cancer:
  • Acute leukaemia cells may have an enzyme deficiency that prevents them from synthesizing asparagine (Asn).
  • Tumour cell growth requires asparagine, which they obtain from healthy tissue.
  • Asparaginase is used to limit tumour growth by removing asparagine available to tumour cells, leading to cell death.
• Skin Ulcers:
  • Severe ulcers can accumulate dead tissue, impairing healing.
  • Topical application of collagenase-containing ointment can promote healing by breaking down dead tissue.

Lipoprotein Lipase Deficiency (Hyperlipidaemia)

• Lipoprotein lipase deficiency results in an inability to digest fat from the diet.
• This leads to elevated chylomicrons, which transport lipids from the digestive tract to the liver.
• Symptoms include pancreatitis, enlargement of the liver and spleen, and xanthomas (yellow skin lesions).
• Management includes limiting fat intake through diet.
• Gene therapy is also a potential treatment.

Gene Therapy

• Direct Treatment:
  • Involves replacing a defective gene with a normal gene directly in the patient's cells.
  • The normal gene is packaged into a virus (using a