Review of Cerliponase Alfa: Recombinant Human Enzyme Replacement Therapy for Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2

Lewis, Grace; Morrill, Amanda M.; Conway-Allen, Stephanie L; Kim, Bernard

doi:10.1177/0883073819895694

Cited by 25 publications

(19 citation statements)

References 10 publications

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“…In both patients these reactions could be well managed by adding corticosteroids (oral dexamethasone 0.15–0.4 mg/kg) to their premedication, with which these reactions did not reoccur. Similar reactions have been observed in patients after cerliponase alfa administration [ 15 , 19 ]. No prolonged hospitalization was required.…”

Section: Resultssupporting

confidence: 80%

Presymptomatic treatment of classic late-infantile neuronal ceroid lipofuscinosis with cerliponase alfa

Schaefers

Giessen

Klees

et al. 2021

Orphanet J Rare Dis

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Background Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare rapidly progressive neurodegenerative disorder, resulting in early death. Intracerebroventricular enzyme replacement therapy (ERT) with cerliponase alfa is now available and has shown to delay disease progression in symptomatic patients. It is yet unknown if cerliponase alfa can prevent disease onset in presymptomatic patients. Results We evaluated the effect of 2 years of intracerebroventricular ERT in two siblings with CLN2 disease, one symptomatic (age 47 months) and one presymptomatic (age 23 months) at treatment start, using the CLN2 Clinical Rating Scale (CLN2 CRS), Gross Motor Function Measure-66 (GMFM-66) for motor function, Bayley Scales of Infant and Toddler Development, 3rd Edition, Dutch (BSID-III-NL) for neurocognitive development, brain MRI, and visual evoked potentials (VEP), electroretinogram (ERG) and retinoscopy for visual function. On the CLN2 CRS patient 1 showed a decline from 3 to 2 in the combined motor and language score due to regression in language use (CLN2 CRS total score after 2 years of treatment: 8), whereas a decline of 2 or more points in the combined motor and language score would be expected without treatment. Patient 2 retained the maximum score of 3 in all 4 subdomains (CLN2 CRS total score after 2 years of treatment: 12). The GMFM-66 total score declined from 46 to 39 in patient 1 and showed an age-appropriate increase from 66 to 84 in patient 2. Cognitive-developmental age decreased from 24 to 11 months in patient 1, whereas an increase in cognitive-developmental age from 21 to 39 months was seen in patient 2. Cerebral and cerebellar atrophy observed on MRI in patient 1 at age 42 months (before treatment) was not observed in patient 2 at age 48 months (after 2 years of treatment). Conclusion We show that cerliponase alfa is able to delay the onset of symptoms when treatment is started in a presymptomatic stage of CLN2 disease. Our results advocate the start of treatment at an early age before symptom onset, but should be confirmed in a larger cohort study.

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Section: Resultssupporting

confidence: 80%

Presymptomatic treatment of classic late-infantile neuronal ceroid lipofuscinosis with cerliponase alfa

Schaefers

Giessen

Klees

et al. 2021

Orphanet J Rare Dis

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“…Unfortunately, there is currently no cure for the NCLs, in large part due to our poor understanding of the proteins associated with the disease. As a result, other than Brineura, which is an enzyme replacement therapy specific for only one subtype of the disease (CLN2 disease), there are currently no effective treatments to prevent or delay the NCLs [6].…”

Section: Neuronal Ceroid Lipofuscinosismentioning

confidence: 99%

Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum

Huber

2020

J Biomed Sci

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The neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, belong to a family of neurological disorders that cause blindness, seizures, loss of motor function and cognitive ability, and premature death. There are 13 different subtypes of NCL that are associated with mutations in 13 genetically distinct genes (CLN1-CLN8, CLN10-CLN14). Similar clinical and pathological profiles of the different NCL subtypes suggest that common disease mechanisms may be involved. As a result, there have been many efforts to determine how NCL proteins are connected at the cellular level. A main driving force for NCL research has been the utilization of mammalian and non-mammalian cellular models to study the mechanisms underlying the disease. One non-mammalian model that has provided significant insight into NCL protein function is the social amoeba Dictyostelium discoideum. Accumulated data from Dictyostelium and mammalian cells show that NCL proteins display similar localizations, have common binding partners, and regulate the expression and activities of one another. In addition, genetic models of NCL display similar phenotypes. This review integrates findings from Dictyostelium and mammalian models of NCL to highlight our understanding of the molecular networking of NCL proteins. The goal here is to help set the stage for future work to reveal the cellular mechanisms underlying the NCLs.

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“…In April 2017, Food and Drug administration approved cerliponase alfa recombinant human tripeptidyl peptidase (TPP)1 for the treatment of NCL2, which is an innovative treatment available for this rare disease. 5 Hence, early diagnosis is important. The NCLs share common clinical features such as epilepsy, neuro-regression, visual impairment, and premature death.…”

Section: Introductionmentioning

confidence: 99%

Neuronal Ceroid Lipofuscinosis: Clinical and Laboratory Profile in Children from Tertiary Care Centre in South India

et al. 2020

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Neuronal ceroid Lipofuscinosis (NCL), inherited disorders of lysosomal storage disorders, constitute the most common progressive encephalopathies with an incidence of 1.3 to 7 in 100,000 live births. We report clinical, electrophysiological, radiological, ultrastructural, and molecular genetic features of NCL. This is a retrospective review, in a tertiary care center from January 2016 to December 2019. All children with clinical features of NCL and confirmed by pathogenic mutation and/or enzyme assay were included. A total of 60 children (male:female = 3:1) were studied. The commonest type was CLN 2 (41.7%). Neuroregression, seizures, and ataxia were present in all cases. Retinal arterial attenuation was seen in 38.33% cases. Magnetic resonance imaging (MRI) brain was abnormal in all patients, thalamic and caudate nucleus atrophy common in CLN1 (62%). Electroencephalography was abnormal in all children, but photoparoxysmal response at low intermittent photic stimulation frequencies was seen in four children of CLN2. Electron microscopy done in 43 children revealed abnormal inclusions in 20 (46.52%) children. Enzyme study showed low levels in 36 (78%) out of 46 cases. Of these, 21 had low tripeptidyl peptidase and 15 had low palmitoyl protein thioesterase levels. Molecular testing done in 26 cases showed pathogenic variant in 23 (88%) cases. Infantile onset with thalamic atrophy on MRI is common in CLN1 and refractory epilepsy, visual impairment and specific EEG changes are common in CLN2. These features are helpful in selecting enzyme assay for CLN1 versus CLN2. Electron microscopy helped in the diagnosis and genetic testing in subtyping. Thus, a multimode approach played a role in the diagnosis of NCL.

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Review of Cerliponase Alfa: Recombinant Human Enzyme Replacement Therapy for Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2

Cited by 25 publications

References 10 publications

Presymptomatic treatment of classic late-infantile neuronal ceroid lipofuscinosis with cerliponase alfa

Presymptomatic treatment of classic late-infantile neuronal ceroid lipofuscinosis with cerliponase alfa

Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum

Neuronal Ceroid Lipofuscinosis: Clinical and Laboratory Profile in Children from Tertiary Care Centre in South India

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