TY - JOUR
T1 - Cerliponase Alfa for the Treatment of Atypical Phenotypes of CLN2 Disease
T2 - A Retrospective Case Series
AU - Wibbeler, Eva
AU - Wang, Raymond
AU - Reyes, Emily de los
AU - Specchio, Nicola
AU - Gissen, Paul
AU - Guelbert, Norberto
AU - Nickel, Miriam
AU - Schwering, Christoph
AU - Lehwald, Lenora
AU - Trivisano, Marina
AU - Lee, Laura
AU - Amato, Gianni
AU - Cohen-Pfeffer, Jessica
AU - Shediac, Renée
AU - Leal-Pardinas, Fernanda
AU - Schulz, Angela
N1 - Funding Information:
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EW, MN, CS, LLeh, and MT are investigators in cerliponase alfa clinical studies for BioMarin and have received honoraria from BioMarin. RW owns equity interest in and has received honoraria and research grants from BioMarin. AS, EdlR, NS, and PG are investigators in cerliponase alfa clinical studies for BioMarin and have received consulting fees and grants from BioMarin. NG has received honoraria and research grants from BioMarin. LLee is an investigator in cerliponase alfa clinical studies and has received grants from BioMarin. GA is a consultant for BioMarin. JCP, RS, and FLP are employees and shareholders of BioMarin.
Publisher Copyright:
© The Author(s) 2020.
PY - 2021/5
Y1 - 2021/5
N2 - Background: The classic phenotype of CLN2 disease (neuronal ceroid lipofuscinosis type 2) typically manifests between ages 2 and 4 years with a predictable clinical course marked by epilepsy, language developmental delay, and rapid psychomotor decline. Atypical phenotypes exhibit variable time of onset, symptomatology, and/or progression. Intracerebroventricular-administered cerliponase alfa (rhTPP1 enzyme) has been shown to stabilize motor and language function loss in patients with classic CLN2 disease, but its impact on individuals with atypical phenotypes has not been described. Methods: A chart review was conducted of 14 patients (8 male, 6 female) with atypical CLN2 phenotypes who received cerliponase alfa. Pre- and posttreatment CLN2 Clinical Rating Scale Motor and Language (ML) domain scores were compared. Results: Median age at first presenting symptom was 5.9 years. First reported symptoms were language abnormalities (6 [43%] patients), seizures (4 [29%]), ataxia/language abnormalities (3 [21%]), and ataxia alone (1 [7%]). Median age at diagnosis was 10.8 years. ML score declined before treatment in 13 (93%) patients. Median age at treatment initiation was 11.7 years; treatment duration ranged from 11 to 58 months. From treatment start, ML score remained stable in 11 patients (treatment duration 11-43 months), improved 1 point in 1 patient after 13 months, and declined 1 point in 2 patients after 15 and 58 months, respectively. There were 13 device-related infections in 8 patients (57%) and 10 hypersensitivity reactions in 6 (43%). Conclusions: Cerliponase alfa is well tolerated and has the potential to stabilize motor and language function in patients with atypical phenotypes of CLN2 disease.
AB - Background: The classic phenotype of CLN2 disease (neuronal ceroid lipofuscinosis type 2) typically manifests between ages 2 and 4 years with a predictable clinical course marked by epilepsy, language developmental delay, and rapid psychomotor decline. Atypical phenotypes exhibit variable time of onset, symptomatology, and/or progression. Intracerebroventricular-administered cerliponase alfa (rhTPP1 enzyme) has been shown to stabilize motor and language function loss in patients with classic CLN2 disease, but its impact on individuals with atypical phenotypes has not been described. Methods: A chart review was conducted of 14 patients (8 male, 6 female) with atypical CLN2 phenotypes who received cerliponase alfa. Pre- and posttreatment CLN2 Clinical Rating Scale Motor and Language (ML) domain scores were compared. Results: Median age at first presenting symptom was 5.9 years. First reported symptoms were language abnormalities (6 [43%] patients), seizures (4 [29%]), ataxia/language abnormalities (3 [21%]), and ataxia alone (1 [7%]). Median age at diagnosis was 10.8 years. ML score declined before treatment in 13 (93%) patients. Median age at treatment initiation was 11.7 years; treatment duration ranged from 11 to 58 months. From treatment start, ML score remained stable in 11 patients (treatment duration 11-43 months), improved 1 point in 1 patient after 13 months, and declined 1 point in 2 patients after 15 and 58 months, respectively. There were 13 device-related infections in 8 patients (57%) and 10 hypersensitivity reactions in 6 (43%). Conclusions: Cerliponase alfa is well tolerated and has the potential to stabilize motor and language function in patients with atypical phenotypes of CLN2 disease.
KW - CLN2 disease
KW - atypical
KW - cerliponase alfa
KW - late infantile neuronal ceroid lipofuscinosis
KW - natural history
KW - neuronal ceroid lipofuscinosis type 2
UR - http://www.scopus.com/inward/record.url?scp=85097985053&partnerID=8YFLogxK
U2 - 10.1177/0883073820977997
DO - 10.1177/0883073820977997
M3 - Article
C2 - 33356800
AN - SCOPUS:85097985053
SN - 0883-0738
VL - 36
SP - 468
EP - 474
JO - Journal of Child Neurology
JF - Journal of Child Neurology
IS - 6
ER -