Enzyme Replacement Therapy

Batten disease, also known as neuronal ceroid lipofuscinosis (NCLs), is a severe neurological condition caused by genetic mutations. These mutations result in defective or absent enzymes that normally help to break down waste material inside cells. Without these enzymes, or without them working as they should, a yellow-white fatty substance called lipofuscin accumulates within cells, to levels that become toxic. Nerve cells are particularly sensitive to a buildup of lipofuscin.

Enzyme replacement therapy can help treat Batten disease by replacing a patient’s missing or deficient enzyme with a fully functional one. This can help restore the proper breakdown of waste material within cells, and prevent cell death.

How enzyme replacement therapy works

Enzyme replacement therapy is used to treat diseases where there are mutations in genes that cause the enzyme they encode for to either malfunction or go missing. This therapy supplies the functional enzyme to patients.

However, enzyme replacement therapy is not a cure for a disease, and requires lifelong administration of the enzyme. If treatment is stopped, disease symptoms will return.

Enzyme replacement therapy for Batten disease

Batten disease may be caused by mutations in any one of 14 genes, affecting different enzymes. There is not one enzyme that can be targeted to treat all forms of Batten disease.

As Batten affects the brain and nervous system, its treatments must reach the brain to be effective. But getting the proper enzyme to cross the blood brain barrier can be difficult.  For this reason, enzyme replacement therapy can only be used in Batten forms where the affected enzyme is soluble. This includes the subtypes known as CLN1 disease (infantile Batten), CLN2 disease (late-infantile Batten), CLN5 disease (also known as Jansky-Bielschowsky disease), and CLN10 disease (congenital Batten).

  • CLN1 disease affects the palmitoyl-protein thioesterase 1 (PPT1) enzyme that breaks down fatty acids.
  • CLN2 disease affects the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1) that breaks down proteins.
  • CLN5 disease affects the protein encoded by the CLN5 gene. The exact function of this protein is not known, but it is thought to affect the breakdown and recycling of material found in lysosomes.
  • CLN10 disease affects the cathepsin D enzyme that modifies other proteins by cutting them apart.

Brineura (cerliponase alfa)

Currently, one enzyme replacement therapy is approved to treat Batten disease — Brineura (cerliponase alfa), developed by BioMarin Pharmaceuticals for the treatment of CLN2 disease. Brineura works to replace the TPP1 enzyme missing in CLN2 disease. The treatment has been shown to help slow the progressive loss of walking ability in CLN2 patients. Brineura was approved by the U.S. Food and Drug Administration (FDA) in April 2017 and by European Medicines Agency (EMA) in June 2017.

Enzyme replacement therapies like Brineura must be infused directly into the fluid surrounding the brain, via a method known as intraventricular infusion. Before an intraventricular infusion treatment can begin, an intraventricular access device must be surgically placed in a patient’s skull.


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