RESEARCH PROJECT

Detecting and Measuring Eye Movement Abnormalities in Children with Brain Injury

Aims 

• The overall goal of this 2-year project is to develop practical techniques for quantitative measurement of eye movement abnormalities as an indicator of neurological disease in infants and non-instructable children.
• The main focus will be on young children with neurological hereditary metabolic diseases (nHMDs) because it is extremely urgent to assess the new potential therapies that are currently being developed. We will also use these techniques for early diagnosis and monitoring of children with other early-onset neurological diseases.
• By acquiring these data, we hope to gain better insight into both normal and abnormal development of the young brain.

Background

We are entering a new era for the treatment of hereditary metabolic diseases (HMDs). The vanguard has been the successful introduction of enzyme replacement therapy (cerezyme ®). Now, treatments for Fabry’s disease and MPS1 are underway. Trials are being developed (or ongoing) for Gaucher disease type 3, Niemann Pick type C, GM2, infantile and late-onset Pompe, MPS 2,4,6 & 7, and Niemann Pick B. Many other compounds have been registered on US and EU orphan drug registers for HMDs. These are exciting new developments for current and future affected children and their families.

Many HMDs are associated with neurological disease, which may be rapidly progressive and fatal in infancy, or chronic but relentless into adolescence or adulthood. Neurological signs and symptoms vary depending on the specific nHMD. The social and familial burdens are incalculable, and place extraordinary emphasis on early treatment.

For nHMDs the new potential drug therapies must halt (ideally reverse) the neurological disease as well as correct for the systemic biochemical abnormality. Unfortunately, these do not go hand-in-hand, as illustrated by ERT in the treatment of Gaucher disease (GD). The reason for this disparity is not entirely clear but probably results from the impermeability of the blood brain barrier to the large enzyme-replacement molecule. Thus, ERT may afford a longer life, but a life with possibly slowly progressive neurological involvement. Therefore, new trials have been started to test a small substrate-restriction (or -reduction) molecule (OGT-918) on Gaucher type 3 disease, which is known to cross the blood brain barrier, and may hopefully halt neurological progression.

A fundamental problem in testing any treatment for neurological disorder is to find a suitable marker for any changes in neurological function. The problem becomes especially difficult in younger children and infants. In the OG-918 trials, eye movements are being measured for the first time as primary outcome measures. The reason for this is that abnormal eye movements are usually the first sign of neurological disease in Gaucher type 3 disease, and can be measured quantitatively. Eye movement abnormalities are also common in many other nHMDs (although detailed quantitative studies have not been made). Thus, eye movements may be a useful way to monitor the time-course of the neurological component of a disease.

The purpose of this project is to find ways of quantitatively measuring eye movements in infants and young children, who cannot be instructed or are unable to cooperate fully for the standard tests used for adults.

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