Considerations and Bayesian Applications in Pharmaceutical Development for Rare Diseases
Mani Lakshminarayanan, Fanni Natanegara in Bayesian Applications in Pharmaceutical Development, 2019
Batten disease is a fatal rare disease of the nervous system that typically has onset of symptoms in childhood and causes worsening problems with vision, movement, and thinking ability.39,40 It is usually referring to a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), to which CLN2 disease belong. CLN2 disease is also known as tripeptidyl peptidase-1 (TPP1) deficiency. In the late infantile form of the CLN2 disease, signs and symptoms typically begin between ages 2 and 4. The initial symptoms usually include language delay, recurrent seizures (epilepsy), and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision loss. CLN2 disease affects essential motor skills, such as sitting and walking. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens. Batten disease collectively is relatively rare, occurring in an estimated two to four of every 100,000 live births in the United States.41
External Control Using RWE and Historical Data in Clinical Development
Harry Yang, Binbing Yu in Real-World Evidence in Drug Development and Evaluation, 2021
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.
Inborn errors of metabolism
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
Other important sphingolipidoses, almost all autosomal recessive in inheritance, include Gaucher disease, Niemann-Pick disease, metachromatic leucodystrophy and generalised gangliosidosis. Batten disease had no specific enzyme defect known until positional cloning identified one form on chromosome 16, with one particularly frequent mutation, allowing, for the first time, prenatal diagnosis for some families with this devastating disorder (see also Chapter 14). The genes involved in the other forms of Batten disease have since been identified.
Progress in gene and cell therapies for the neuronal ceroid lipofuscinoses
Published in Expert Opinion on Biological Therapy, 2018
Anthony Donsante, Nicholas M Boulis
CLN4 disease has not yet been addressed in rodent or large animal models. This form of Batten disease is unique in that it is inherited in an autosomal dominant manner. Rather than causing haploinsufficiency, in vitro and in vivo data suggest that the primary problem is a gain of function resulting in protein aggregation [61,62]. Protein aggregation is a common theme in neurodegenerative disorders [63]. For CLN4, the toxicity may involve the sequestering of PPT1, resulting in a deficiency akin to CLN1 disease [64]. Knockdown or deletion of the mutant allele could be a potential route to therapy for this disease [65], as has been previously done for other proteins such as superoxide dismutase 1 in amyotrophic lateral sclerosis [66].
Related Knowledge Centers
- Bruxism
- Constipation
- Nervous System
- Visual Perception
- Hyperventilation
- Echolalia
- Dominance
- Neuronal Ceroid Lipofuscinosis
- Kufs Disease
- Seizure