Lysosomal storage diseases arise because of genetic mutations that result in nonfunctioning or dysfunctional lysosomal
enzymes responsible for breaking down molecules such as
glycosaminoglycans or
glycogen. Many of these storage diseases, such as the
mucopolysaccharidosis (MPS) disorders and
Pompe disease, can now be treated with infusion
therapies to replace the dysfunctional
protein with active
enzyme. Although these
therapies are effective, in at least one condition, infantile-onset
Pompe disease,
antibodies that develop against the
drug significantly reduce its efficacy. However, this influence on efficacy does not appear to manifest across all
enzyme replacement therapies. An example is
MPS IVA, or Morquio A syndrome, in which the
glycosaminoglycans keratan sulfate and chondroitin-6-sulfate accumulate in tissues as a result of N-acetylgalactosamine-6-sulfatase deficiency. The current approved treatment for
MPS IVA is
elosulfase alfa, a recombinant human
enzyme replacement therapy. Although all patients receiving
elosulfase alfa treatment develop antidrug
antibodies and most develop
neutralizing antibodies, clinical data to date show no effect on
drug efficacy or safety. Overall, the relevance of antidrug
antibodies specific to
enzyme replacement therapies for the
lysosomal storage diseases remains a mixed picture that will require time and continued clinical follow-up to resolve for each specific condition and treatment.