Combined brain- and eye-directed gene therapy in ovine Batten disease

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Status: In-progress
Year: 2019
Funded: $2,019
Grant Type: Major Project Grant
Tags:
Research

Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of inherited neurodegenerative diseases of childhood with a worldwide incidence of 1:12,500 live births. Affected children lose their vision, suffer seizures and experience physical and cognitive decline. There is currently no cure.

Lincoln University has unique flocks of sheep with a naturally occurring CLN5 variant of Batten disease. Clinical and neuropathological disease progression is well defined in these sheep which have proven to be excellent models of the human condition. Corrective gene therapy delivered to the brains of CLN5 affected sheep showed exciting results, protecting against stereotypical brain atrophy and clinical decline, as monitored by in vivo non-invasive methods and verified post mortem. 

We are in the final stage of bringing this therapy into human clinical trials. However treated sheep still went blind, but recent findings from a pilot study of ocular gene therapy were encouraging. Gene therapy to one eye of affected sheep provided long term protection from loss of retinal cell activity compared to the untreated eye.

We plan to trial combined brain- and eye-directed gene therapy in both pre- and post-symptomatic CLN5 sheep in an effort to prevent both neurological disease and retinal degeneration simultaneously.

Researcher // Dr Samantha Murray – Lincoln University

Dr Murray is a Post-Doctoral Fellow at Lincoln University within the Faculty of Agriculture and Life Sciences.

BattenDisease

What is Batten Disease?

Batten disease is a fatal disease of the nervous system that typically begins in childhood. Onset of symptoms is usually between 5 and 10 years of age. Often, it is autosomal recessive. It is the most common form of a group of disorders called the neuronal ceroid lipofuscinoses (NCLs). Although Batten disease is usually regarded as the juvenile form of NCL (or “type 3”), some physicians use the term Batten disease to describe all forms of NCL. Historically, the NCLs were classified by age of disease onset as infantile NCL (INCL), late infantile NCL (LINCL), juvenile NCL (JNCL) or adult NCL (ANCL). At least 20 genes have been identified in association with Batten disease, but juvenile NCL, the most prevalent form of Batten disease, has been linked to mutations in the CLN3 gene.

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There are 14 known forms of Batten disease often referred to as CLN1-CLN14.
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If both parents carry one defective gene, there is a 1 in 4 chance during each pregnancy of having a child with the disease.
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There is also a 1 in 4 chance for baby to inherit two completely normal genes.
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There is a 50% chance for baby to inherit only one copy of the defective gene, making it a “carrier” like the parent.

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