Enzyme therapy shows promise for infantile Batten disease

Enzyme therapy shows promise for infantile Batten disease
P © iStock/Serhii Sobolevskyi

A new study finds potential treatment for infantile Batten disease, a condition that causes dementia and early death in children.

Infantile Batten disease, also known as CLN1 disease, is a rare, inherited disorder of the nervous system. With this condition, symptoms are seen before age one and progress rapidly. It causes developmental skills such as standing, walking, and talking to be either not achieved or gradually lost. Impacted children may develop seizures by age two and eventually become blind. By three years of age, children may become dependent on their caregivers, and some may require a feeding tube. These children die in early to mid-childhood.

The study conducted by the University of Edinburgh and Washington University School of Medicine found that regular infusions of a key enzyme that is deficient in children with infantile Batten disease led to improvements in mice and sheep with an equivalent genetic disorder.

Enzyme infusion for infantile Batten disease

Scientists studied the effect of administering doses of the enzyme, known as PPT1, in mice and sheep with the same faulty gene that causes infantile Batten disease in children.

Monthly doses of the PPT1 enzyme to the brains of mice led to improved motor function, reduced signs of disease in brain cells, and reduced loss of brain matter over six months of treatment.

To test the enzyme, the researchers verified the dosage of the enzyme and how to administer the dose correctly and then determined effective enzyme infusion treatments for the affected sheep. It was important to test if the treatments could be scaled up to have a similar positive treatment effect in a larger brain.

The University of Edinburgh study is based on a similar approach for a different form of Batten disease called CLN2 which has led to a therapy called cerliponase alfa. This has been approved by the NHS following successful trials across the world. The researchers used mice to initially test the effects of the therapy and then refined it using sheep whose brain size and complexity are comparable to that of children.

Employing genome editing to create a new treatment

The researchers developed a sheet model for infantile Batten disease using genome editing technology called CRISPR so that therapeutic studies can be completed. This enabled researchers to understand the mechanisms behind the progression of the condition and to assess methods of managing the condition. The animals showcased distinctive features of the disease in children.

“This study could only have been done by a collaborative research team. Such work is a key step towards everyone’s ultimate goal of safely carrying out clinical tests of potential treatments in children affected by this devastating condition. Through studies in sheep, we gain invaluable insights into the progression of this condition which can guide our work towards developing an effective therapy,” commented Professor Tom Wishart, Professor of Molecular Anatomy at the University of Edinburgh’s Roslin Institute.

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