The following article features coverage from the 17th Annual WORLDSymposium meeting. Click here to read more of MPR’s conference coverage.
Extending enzyme replacement therapy (ERT) beyond the standard 8-week period following hematopoietic cell transplantation (HCT) appears to provide neurocognitive benefit for patients with Hurler syndrome, according to research presented the 17th Annual WORLDSymposium.
A hallmark feature of Hurler syndrome, a severe form of mucopolysaccharides (MPS) type I, is neurocognitive decline. Treatment of this disease typically includes a combination of HCT, which halts neurocognitive decline, plus ERT to reduce transplant-related morbidity and mortality and potentially provide a neurocognitive benefit. “In the past 10 years, our institution has offered the option to continue ERT beyond the standard 8 weeks following transplant, with the rationale that organ function and somatic outcomes may be further improved,” the study authors explained.
During the assessment, the study authors compared the outcomes of patients in 2 groups. The Extended group included 9 children with Hurler syndrome who received ERT for at least 1 year after HCT. “We matched these children for age at HCT with 9 patients who received HCT + ERT for the standard period, ie, 8 weeks following HCT (Standard group),” the authors explained.
Neurocognitive function, such as early IQ, was measured with the Mullen Scales of Early Learning or Bayley Scales of Infant and Toddler Development 3rd Edition (population IQ mean, 100 ± 15; average range, 85-115). The group level IQ means were reported to be 95 for the Extended group and 89 for the Standard group prior to transplantation. It was noted that all but 1 patient in each group measured within the average range.
Findings of the analysis revealed that extending the duration of ERT after HCT may provide neurocognitive benefit. Study authors reported that 1 year after HCT, Extended patients showed a mean loss of 9 IQ points, whereas Standard patients showed a mean loss of 14 points. One year after HCT, group level IQ means were found to be 86 for the Extended group and 75 for the Standard group. “Individual patient analysis revealed that 7 Standard patients fell below the average range at 1 year post-HCT, whereas only 3 Extended patients had this outcome, ie, the majority of Extended patients remained in the average range intellectually,” the authors added.
The study had several limitations, including participants not randomized to groups, possible economic disparities between groups (eg, access to transportation, SES, etc), and different IQ measures used across time points for some patients.
The study authors concluded that additional potential factors will need to be controlled to determine if extended ERT slows the rate of cognitive decline early in the peri-transplant period. Further studies using larger sample sizes and longer treatment periods are warranted at this time.
Gimbel B, Gupta A, Orchard PJ, Lund T, Eisengart JB. Does extending enzyme replacement therapy after transplant provide neurocognitive benefit in Hurler syndrome? Presented at: 17th Annual WORLDSymposium; February 8-12, 2020. Abstract 082.