Leber Congenital Amaurosis

Leber Congenital Amaurosis (LCA) is a rare genetic eye disease that appears at birth or in the first few months of life. The extent of vision loss varies from patient to patient, but can be quite severe (with little to no light perception). LCA is actually a term given to a group of diseases that are caused by mutations in at least 14 genes. The gene mutations lead to failure in function of the photoreceptor cells (rod and cones cells that receive light), ultimately causing cell degeneration. Given the severity of the condition, it is one of the most extensively researched inherited retinal disorders (IRDs), and a number of clinical trials have begun recently.

What are the symptoms of LCA?

There are many different types of LCA, and the disease can present differently in different children. However, there are some basic symptoms that are often associated with LCA. These include nystagmus (involuntary jerky rhythmic eye movement), photophobia (sensitivity to light) and slow pupillary response to light. Eye-pressing and rubbing the eyes with a knuckle or finger can be common with babies and children who have very little vision. This can cause damage to the cornea (keratoconus) and lens and may result in a loss of fatty tissue around the eyes causing the eyes to look deep-set. The extent of degeneration depends on the type of LCA the child has and for some types of LCA the vision (or lack of vision) remains stable.

What is the cause of LCA and how is it inherited?

LCA is a very rare condition which is estimated to affect around 1 in 80,000 in the population. Forms of LCA are caused by a mutation in one of a number of genes that are important for retinal function and it is usually inherited in an autosomal recessive manner. However, there are rare incidences where the inheritance pattern may be autosomal dominant.

What treatments are available?

At present, there are no treatments for LCA. However a number of clinical trials on-going with some at an advanced stage where a small number of patients on trials have been successfully treated. 

Gene therapy for a form of LCA known as LCA2 has gathered momentum in recent years. In the LCA2 clinical trials, gene replacement therapy involves engineering a “normal” copy of the RPE65 gene in the laboratory and injecting harmless viral particles containing the gene into the back of the eye to allow integration of the gene into the DNA. Encouragingly, there have been no safety issues reported with these clinical trials to date and improvements in vision have been observed. These trials are on-going, and more trials for other subtypes of LCA are planned to begin recruitment in the near future.

Promising human clinical trials investigating an oral drug are also underway in forms of LCA caused by alterations in the RPE65 gene or the LRAT gene. These therapies aim to improve vision by bypassing the biochemical effects of lack of RPE65 or LRAT and thus “reawakening” dormant or sleeping retinal cells in order to allow the patient to see. It is extraordinary that this very uncommon, and severe, inherited retinal degeneration is the subject of different clinical trials, which have shown early evidence of success. This gives justifiable hope that less severe inherited retinal degenerations might also be treatable in the foreseeable future.

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