Inherited retinal dystrophies are rare ophthalmic pathologies that can be divided into two groups:

1. pigmentary retinopathies, which include retinitis pigmentosa (RP) and Leber congenital amaurosis
2. macular dystrophies

Retinitis pigmentosa is the most common form of inherited retinal dystrophy representing 50% of all retinal dystrophies.

While multiple genes are implicated in each of these groups, within each patient or family, only one causative gene is involved.

PDE6b RP is an inherited retinal dystrophy that leads to blindness by midlife and is characterized by the progressive loss of photoreceptors, with or without the loss of retinal pigment epithelium cells.

It is caused by mutation of the PDE6b gene resulting in dysfunctional Rod PDE6, an enzyme found in rod outer segments that plays a key role in the phototransduction cascade in rods (the process by which light is converted into electrical signals). Dysfunction of the PDE6 protein, and in particular its PDE6ß subunit, ultimately leads to death of rod photoreceptor cells, then cone photoreceptor cells, leading to blindness.

Mutation of PDE6b is one of the most prevalent human mutations within autosomal recessive RP and accounts for 2-4% of RP cases.

There are currently no approved treatments for PDE6b RP.

Stargardt’s Disease is an inherited retinal dystrophy affecting the macula, a part of the retina. It leads to gradual visual loss and blindness. It is the leading cause of childhood blindness.

The gene responsible for autosomal recessive Stargardt’s Disease, ABCA4, encodes an ABC transporter expressed in the cones and rods of the retina. The loss of ABCA4 function results in the accumulation of cytotoxic retinoids, leading to the death of photoreceptors and retinal pigment epithelium, and leads to progressive vision loss.

There is currently no treatment available for Stargardt’s disease.

CTx-ABCA4 is an optimized coAAV based gene therapy designed to deliver a full-length non-mutated copy of a functional human ABCA4 gene into the subretinal space.

Parkinson’s disease is a severe and progressive neurodegenerative disorder that affects more than seven million people worldwide.

Population-based genetic studies have recently identified several causative and risk genes for Parkinson’s disease. Many of these genes are involved in the normal functioning of lysosomes, a cell organelle containing enzymes responsible for degrading biomolecules.

The GBA1 gene encodes the lysosomal enzyme beta-glucocerebrosidase (GCase), which is needed for the disposal and recycling of glycolipids — a type of cellular lipid component that is known to accumulate with aging. Mutations in the GBA1 gene lead to a deficiency of GCase and are associated with earlier onset of Parkinson’s disease, with more severe symptoms, and increased likelihood of progression to dementia.

There are currently no approved therapies that modify the course of Parkinson’s disease or the underlying pathological process.

Gaucher disease is a lysosomal storage disorder caused by mutations in both copies of the GBA1 gene, which can have a wide range of effects on organs throughout the body. Gaucher disease has three subtypes (Type 1, 2 and 3), which vary by the presence or absence of neurological symptoms, severity of symptoms, age of onset and age at death.

Type 2 and Type 3 Gaucher diseases are the most severe forms and are present in either childhood or adulthood. They involve neurological symptoms and, in infants or toddlers (Type 2), cause rapid and irreversible brain damage beginning in the first six months of life.

Enzyme replacement therapies (ERTs) are approved for the treatment of Type 1 Gaucher disease but are only effective in treating the peripheral symptoms of disease, since they cannot cross the blood brain barrier. There are currently no approved therapies for the neurologic manifestations of Gaucher disease.

September, 15 — 2021

Gene Therapy Research Scientist

In your role as a member of our Research Team, you will contribute to the advancement of our platform and discovery programs. Using your expertise in vector biology, molecular and cell biology, and bioanalytics you will work with a team of junior scientists and lead from the bench to expand our AAV platform and pipeline projects.