China
Africa
Explore chapters and articles related to this topic
Real-World Data and Real-World Evidence
Published in Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow, Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
Cerliponase alfa (Brineura), an enzyme-replacement therapy, was approved in 2017 by FDA as the first treatment for neuronal ceroid lipofuscinosis type 2 (CLN2) disease. CLN2 disease, also known as late infantile neuronal ceroid lipofuscinosis (NCL) is a rare, autosomal recessive, pediatric neurodegenerative disease caused by gene mutation and is featured by difficulty in coordinating movements (ataxia). Patients often progressed to use of a wheelchair by late childhood. There were no other approved pharmacological treatments for CLN2 other than drugs for symptom management.
External Control Using RWE and Historical Data in Clinical Development
Published in Harry Yang, Binbing Yu, Real-World Evidence in Drug Development and Evaluation, 2021
Qing Li, Guang Chen, Jianchang Lin, Andy Chi, Simon Davies
Batten disease, which is also called neuronal ceroid lipofuscinoses (NCLs), is a family of rare, fatal, inherited disorders of the nervous system. It is estimated that 2–4 births per 100,000 in the United States are affected by Batten disease, which is considered as a rare disease. Batten disease was named after British pediatrician Frederick Batten, who first described the disease in 1903; however, there were no approved drugs until recently. In April 2017, the FDA approved Brineura® (cerliponase alfa), which was developed by BioMarin Pharmaceutical, Inc. as a treatment for a specific form of Batten disease (FDA 2017c). It is the first FDA-approved treatment to slow the loss of walking ability (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency. The BLA of Brineura® received priority review and breakthrough therapy designation.
Rheumatology
Published in Paul Bentley, Ben Lovell, Memorizing Medicine, 2019
Chronic:Strategy: Wait >1 month after acute attack; cover for 3 months with NSAID or colchicine; continue indefinitely, incl. during attacksAllopurinol (xanthine oxidase inhibitor): Indicated in ‘overproducers’ or severe disease : Hypersensitivity reaction or rash – necessitates withdrawal; dyspepsiaRasburicase = oxidases uric acid into allantoinUricosuric (probenecid; NSAIDs, e.g. sulphinpyrazone, phenylbutazone): Indicated in ‘underexcretors’, mild disease, preserved renal function : Renal stones (ensure high fluid intake, render urine alkali, e.g. K citrate)
Advances in the treatment of neuronal ceroid lipofuscinosis
Published in Expert Opinion on Orphan Drugs, 2019
Jonathan B. Rosenberg, Alvin Chen, Stephen M. Kaminsky, Ronald G. Crystal, Dolan Sondhi
CLN2 disease, also known as late infantile neuronal ceroid lipofuscinosis (LINCL), is caused by mutations in the CLN2 gene, which encodes the lysosomal protein tripeptidyl peptidase 1 (TPP1) [46]. Affected children usually display symptoms of the disease by ages 2 to 4, typically starting with recurrent seizures and difficulty in coordinating movements [47,48]. The disease progresses with developmental regression, affecting speech and motor skills. Actions such as sitting and walking become more difficult, as does swallowing. Affected children also develop myoclonus, vision loss, and intellectual disabilities, and typically do not survive past 8 to 12 years [47]. Natural history observational studies have linked genotype and the severity of the phenotype, and the rate of neurologic decline has also been determined [47,49,50]. In an MRI study analyzing CLN2 children (n = 38) compared to healthy controls (n = 52), global thinning of the cortical regions was noted across the brain [49]. In newer observational studies for the same set of CLN2 subjects and healthy controls, MRI was used to measure the regional cortical thickness in the brain, which appears to be 2X thicker in controls vs CLN2 subjects, demonstrating the overall declining neurologic health of the CLN2 children [50]. In a recent study, which used the same methods of assessment for patient cohorts in the US and Europe, the natural history of children afflicted with CLN2 was defined, characterizing a predictable time frame of decline of language and motor skills [51].
Ocular Manifestations of Neuronal Ceroid Lipofuscinoses
Published in Seminars in Ophthalmology, 2021
Rohan Bir Singh, Prakash Gupta, Akash Kartik, Naba Farooqui, Sachi Singhal, Sukhman Shergill, Kanwar Partap Singh, Aniruddha Agarwal
CLN-2 gene associated CLN-2 disease (earlier known as Jansky-Bielschowsky disease) is characterized by progressive neurodegeneration and accumulation of hydrophobic autofluorescent material in the cytoplasm of neurons.38 CLN-2 in its classical form presents as late infantile neuronal ceroid lipofuscinosis (LINCL) with the onset of symptoms usually between 2 and 4 years of age with death in early adolescence between 10 and 15 years of age.39–43 The estimated incidence has been estimated to be <0.5 per 100,000 live births.44