Gene therapy for the eye Courtesy of the Laboratory of Dr Sara Mole and Prof Robin Ali, University College London s.mole@ucl.ac.uk

Yeasts: simple

•  Loss of vision is one of the first symptoms in (juvenile) Batten disease and precedes severe neurological symptoms. Early on it reduces significantly the quality of life of patients and affected families.

•  A therapy for the eye may delay the onset of the visual decline or slow down the progression of the visual decline and would improve quality of life enormously. Moreover, it may give useful insight for the development of therapies targeting other organs, like the brain.

What is the purpose of a therapy for the eye?

Ophthalmology Volume 107, Number 9, September 2000

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Ophthalmology Volume 107, Number 9, September 2000

1750

Healthy control 33 years Patient 22 years

Bensaoula et al ! Ocular Pathology in Batten Disease

1749

Bensaoula et al ! Ocular Pathology in Batten Disease

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The human eye

•  The retina is a light-sensitive tissue lining the inner surface of the eye. It consists of three cell layers:

•  The major i ty of ce l ls in the ret ina are photoreceptors, cells that are located in the outer most layer of the retina. These cells are specialized to detect light and play therefore an essential role for vision.

•  In juvenile Batten disease vision declines at the age of 6 to 8 years and results in total blindness within a few years.

•  Vision is lost due to the death of photoreceptors.

 

 

light sensitive cells (photoreceptors)

3 layers of cells

 

The retina is severely thinned in juvenile Batten disease patients compared to a healthy person:

Retinal defect in juvenile Batten disease

Retina Retina

Retina Retina

•  Cells (labeled in blue) are lost in all layers of the retina.

•  Widespread act ivat ion of immune cells (green) indicates an increased inflammation in patient’s retina.

Schematic retina

•  Only a few photoreceptor cells (red) are left in patients.

Why gene therapy? •  Batten disease is an inherited disorder that is caused by a genetic defect. •  Gene therapy is an approach to achieve treatments for diseases that arise from mutations in

genes. A gene therapy aims to reintroduce healthy copies of a missing gene through the administration of a virus that carries healthy copies of the affected gene.

•  Viruses that carry healthy copies of a gene can be produced in the laboratory in large quantities.

•  Over the last decade gene therapy has been used for a variety of genetic disorders to slow down or halt the disease progression.

•  Researchers in Prof Robin Ali’s lab at the Institute of Ophthalmology at UCL could show that gene therapy leads to improved vision in animals presenting with different genetic disorders affecting the eye. Clinical trials are currently on-going for Leber congenital amaurosis, a gene defect causing the degeneration of the retina.

•  Gene therapy has also been used for animal models representing Batten disease and showed

promising data. In addition, there is a clinical trial on-going for late-infantile Batten disease targeting the brain. However, the eye defect in Batten disease has not been focused on yet and a therapy targeting the brain is not likely to have an effect on the retinal degeneration in Batten disease.

Administration of virus One strategy to deliver virus to photoreceptor cells in the retina is subretinal injection. For this procedure, the virus is injected underneath the retina, which leads to a temporary detachment of the retina. Over time the detachment resolves. Subretinal injections are currently used in clinical trials for other ocular diseases.

Reference patient image:

Bensaoula T, Shibuya H, Katz ML, et al. Histopathologic and immunocytochemical analysis of the retina and ocular tissues in Batten disease. Ophthalmology. 2000;107(9):1746–1753

Healthy control 33 years Patient 22 years