Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial

Wijburg, Frits A.; Whitley, Chester B.; Muenzer, Joseph; Gasperini, Serena; Toro, Mireia del; Muschol, Nicole; Cleary, Maureen; Sevin, Caroline; Shapiro, Elsa; Bhargava, Parul; Kerr, Douglas A.; Alexanderian, David

doi:10.1016/j.ymgme.2018.10.006

Cited by 40 publications

(40 citation statements)

References 11 publications

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“…2). Conversely, correction of biochemical defects in the CNS has failed to improve neurocognitive outcomes in most therapeutic trials (17)(18)(19)(20)(21). Among the 12 LSD enzyme replacement or small molecule therapies approved in the United States as of 2018 (40), only 1, intraventricular cerliponase alfa therapy for CLN2 disease, is approved for a neurologic indication (41).…”

Section: Discussionmentioning

confidence: 99%

“…The corollary of this hypothesis is that delayed correction of the underlying deficiency may be insufficient to restore circuit function and improve symptoms. To date, the lack of meaningful clinical benefit of several brain-directed LSD therapeutic trials, despite improving biochemical markers of disease in the CNS, supports this possibility (17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuronal network dysfunction precedes storage and neurodegeneration in a lysosomal storage disorder

Ahrens‐Nicklas¹,

Tecedor²,

Hall³

et al. 2019

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuronal network dysfunction precedes storage and neurodegeneration in a lysosomal storage disorder

Ahrens‐Nicklas¹,

Tecedor²,

Hall³

et al. 2019

JCI Insight

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“…On the other hand, direct brain administration for the treatment of neurological disorders seems more beneficial [ 74 ], although it is an aggressive treatment that needs continued injections. Nevertheless, clinical trials based on ERT for Sanfilippo syndrome type A and B have been carried out without clear results [ 75 , 76 , 77 , 78 ]. In any case, research to further investigate the potential of this approach is required [ 79 ].…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches

Benetó

Vilageliu

Grinberg

et al. 2020

IJMS

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Sanfilippo syndrome or mucopolysaccharidosis III is a lysosomal storage disorder caused by mutations in genes responsible for the degradation of heparan sulfate, a glycosaminoglycan located in the extracellular membrane. Undegraded heparan sulfate molecules accumulate within lysosomes leading to cellular dysfunction and pathology in several organs, with severe central nervous system degeneration as the main phenotypical feature. The exact molecular and cellular mechanisms by which impaired degradation and storage lead to cellular dysfunction and neuronal degeneration are still not fully understood. Here, we compile the knowledge on this issue and review all available animal and cellular models that can be used to contribute to increase our understanding of Sanfilippo syndrome disease mechanisms. Moreover, we provide an update in advances regarding the different and most successful therapeutic approaches that are currently under study to treat Sanfilippo syndrome patients and discuss the potential of new tools such as induced pluripotent stem cells to be used for disease modeling and therapy development.

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“…Announcement from the hospital that the clinical trial (enzyme replacement therapy (34)), in which the child participated, was prematurely terminated (loss of hope, SUD 7)…”

Section: Stressful Memoriesmentioning

confidence: 99%

Reducing posttraumatic stress in parents of patients with a rare inherited metabolic disorder using eye movement desensitization and reprocessing therapy: a case study

Conijn

Haverman

Wijburg

et al. 2020

Preprint

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Background Parents of children with severe inborn errors of metabolism (IEMs) frequently face stressful events related to the disease of their child and are consequently at high risk for developing parental posttraumatic stress disorder (PTSD). Assessment and treatment of posttraumatic stress disorder (PTSD) in these parents is however not yet common in clinical practice. PTSD can be effectively treated by Eye Movement Desensitization and Reprocessing (EMDR), mostly offered in multiple weekly sessions which may preclude participation as parents are generally overburdened by the ongoing and intensive care for their child. We offered time-limited EMDR therapy with a maximum of four sessions over two subsequent days to two parents (from different families) of mucopolysaccharidosis type III (MPS III) patients to explore the potential effect of this approach in reducing post-traumatic stress symptoms and comorbid psychological distress. Methods Both qualitative and quantitative outcomes were used. The case conceptualisation, EMDR sessions and the effects reported by parents are described. The change in the severity of post-traumatic stress symptoms and comorbid psychological distress were evaluated with the Reliable Change Index (RCI). Results All traumatic memories and catastrophic fears of the future reported by parents were successfully processed and neutralized. Parents felt more competent to face future difficulties related to the disease of their child, and no adverse effects were reported. Quantitative outcomes showed a clinically significant decrease in post-traumatic stress symptoms and comorbid psychological distress from pre- to post treatment, and these beneficial effects were maintained at follow-up. Conclusion Time-limited EMDR might be a successful treatment for traumatized parents of children with mucopolysaccharidosis type III, and we suggest that this approach may have a wider application including parents of children with other severe IEMs. More awareness in clinical practice of the need for assessment and treatment of PTSD in parents of children with IEMs is essential to improve the psychosocial wellbeing of both parent and child.

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Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial

Cited by 40 publications

References 11 publications

Neuronal network dysfunction precedes storage and neurodegeneration in a lysosomal storage disorder

Neuronal network dysfunction precedes storage and neurodegeneration in a lysosomal storage disorder

Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches

Reducing posttraumatic stress in parents of patients with a rare inherited metabolic disorder using eye movement desensitization and reprocessing therapy: a case study

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