Adult-onset lysosomal storage disorders produce a range of chronic impairments because inherited deficiencies of lysosomal enzymes allow substrates to accumulate in tissues. Enzyme replacement therapy supplies recombinant enzyme to reduce storage material and has transformed outcomes for several disorders, but effectiveness depends on disease, tissue involvement, timing, and immune response.
Evidence and clinical effects
Randomized and long-term studies led by Caroline van der Ploeg, Erasmus MC, and clinical programs by Priya S. Kishnani, Duke University, show that ERT for late-onset Pompe disease often stabilizes or improves skeletal and respiratory function, reducing disease progression in many adults. Ellen Sidransky, National Institutes of Health, and other experts describe that for Gaucher disease ERT can substantially reduce organomegaly, correct hematologic abnormalities, and improve bone pain and quality of life. These outcomes reflect the mechanism: delivered enzyme catabolizes accumulated substrates in accessible peripheral tissues.
Limits, causes, and biological nuances
Effectiveness is constrained by the blood–brain barrier, which prevents most intravenous enzymes from reaching the central nervous system; therefore, neurocognitive and spinal manifestations commonly seen in some lysosomal disorders respond poorly to standard ERT. Response is also genotype-dependent: certain mutations and advanced preexisting tissue damage limit recovery even when biochemical substrate decreases. Development of anti-drug antibodies can reduce clinical benefit and has been documented in adult patients, creating the need for immune monitoring and, at times, adjunctive strategies.
Consequences and access considerations
Clinically, effective ERT can delay progression, reduce hospitalizations, and improve day-to-day functioning, but it is not curative for established structural damage. Long-term reliance on regular infusions imposes logistic and financial burdens. Globally, access is unequal: high treatment costs and limited specialist centers restrict availability in many regions, producing territorial and cultural disparities in outcomes. Patients diagnosed late or in low-resource settings often experience irreversible loss before therapy begins, worsening prognoses compared with early-treated individuals.
In sum, ERT is a major advance for adult-onset lysosomal storage disorders when disease manifestations are predominantly peripheral and when treatment begins before irreversible damage. Ongoing research, including work by the groups led by Caroline van der Ploeg and Priya S. Kishnani, seeks improved delivery methods and immune management; reviews by Ellen Sidransky and others emphasize combined strategies and equitable access as critical next steps.