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Feb
13

A rare disease a day: Batten Disease

Following on from past installments of “A rare disease a day” Hunter syndrome, Gaucher disease, Tay-Sachs, Morquio syndrome, Fabry disease, Sanfilippo syndrome, Krabbe Disease, Niemann-Pick Disease it is now the turn of Batten Disease.

Batten disease (also known as Spielmeyer-Vogt-Sjögren-Batten disease) is a an autosomal recessive neurodegenerative disorder that begins in childhood. The incidence is  2 to 4 of every 100,000 live births. It’s the commonest form of neuronal ceroid lipofuscinosis (NCL) . Approximately twenty genes are associated with Batten disease, juvenile NCL, the most prevalent form is linked to mutations in CLN3. Symptoms of Batten disease appear at ages 2–10, with vision problems, or seizures, subtle personality / behavior changes, slow learning or regression, repetitive speech or echolalia, clumsiness, or stumbling. Other symptoms include slowing head growth in the infantile form, poor circulation in legs and feet, decreased body fat and muscle mass, curvature of the spine, hyperventilation and/or breath-holding spells, teeth grinding, and constipation. As time progresses children become mentally impaired, with worsening seizures, and progressive loss of sight, speech and motor skills. Children  become blind, bedridden, and demented, and may possibly die.

Studies have looked at gene therapy and stem cell transplantation. Amilodipine prevents apoptotic cell death in Batten disease, the NMDA receptor has been described as a target with memantine as an inhibitor,  Resveratol has been described as a protective approach to oxidative stress. PPT1 inhibitors may act as chaperones . The TPP1 gene which encodes tripeptidyl peptidase I (TPPI), a lysosomal aminopeptidase associated with classic late-infantile neuronal ceroid lipofuscinosis (CLN2 disease) may also be amenable to chaperone therapy. AMPA antagonists also appear to have some effect in mouse models of the disease. Substrate reduction therapy using cysteamine bitartrate has been described as well as upregulation of TPP1 by gemfibrozil and fenofibrate. Recently N-(tert-Butyl) hydroxylamine (NtBuHA) was shown to cleave the thioester linkage in palmitoylated proteins and mediated lysosomal ceroid depletion in cultured cells from INCL patients. In Ppt1(-/-) mice,  NtBuHA crossed the BBB, depleted lysosomal ceroid, suppressed neuronal apoptosis, slowed neurological deterioration and extended lifespan.

A registry for JNCL was recently described which involved parent advocate participation. Batten Disease Support and Research Association provides education advocacy, research support and family support. Nathan’s Battle represents an example of a patient and their family raising money to fund research for this disease.

2 comments

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  1. Julie Conry says:

    The Batten Disease Support and Research Association (BDSRA), headquartered in Columbus, Ohio, welcomes any inquiries from researchers, scientists, or families who are seeking information, assistance, support, or connections to current clinical trial sites, research projects, or RFP information. Our toll-free phone is 800-448-4570 to reach any staff member. Our website, http://www.bdsra.org and open facebook page also feature timely, updated news and research links to the BDSRA annual family conference, research meetings, and services.

    1. sean says:

      Many thanks Julie for adding the additional information! Greatly appreciated.

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