‘Retinal Dystrophies’ or ‘Inherited Retinal Diseases’ are a group of ‘Rare diseases’ that cause irreversible blindness. Retinitis pigmentosa (RP) is the commonest among them. Photoreceptors (PR), an important layer in the retina, is of two types: cones and rods. Cones are maximum at the macula and help in central vision and activities like reading and identifying colours. Rods are distributed all over the retina and help in night vision and side vision. RP is caused by a gradual degeneration of the rods, followed by cones. Affected people notice difficulty in dim-lit areas as an initial symptom. This is followed by a loss of side vision, with many people eventually losing the central vision. People with advanced RP have either a very small area of central vision or may be totally blind. RP most often starts in the first two decades of life and affects both men and women equally. Approximately, 1 in 4000 people in the world have RP. This number is significantly higher in India. There are at least 1.5 million people affected with RP in India. Moreover, since RP is an inherited disorder that runs in families, the disease is not preventable by any means.
Generating transplantable retinal photoreceptors from iPSCs holds tremendous promise to treat RP by replacing the damaged or dysfunctional native photoreceptors with healthy and functional ones. Eyestem has generated Eyecyte-PRP through a patent pending unified protocol. We have already done extensive in vitro characterization of the product and will soon be ready to start animal trials, in collaboration with the National Institute of Immunology, New Delhi, to test efficacy of our product.
The retina is the layer that lines the back of the eye from within. The central part of the retina is the ‘Macula’, the part that is responsible for sharp vision. A healthy retina is absolutely essential for normal vision to be processed. The retina is a complex structure, made up of ten different layers. The most important are two – the retinal pigment epithelium (RPE) and the photoreceptors (PR). There are two different photoreceptor cells- cones and rods. Cones are maximum at the macula, and help in central vision and activities like reading and identifying colours. Rods are distributed all over the retina and help in night vision and peripheral vision.
Retinitis Pigmentosa is a genetic condition caused by a gradual degeneration of the rods, followed by cones.
RP most often starts in the first two decades of life and can affect both men and women. Affected people notice difficulty in dim-lit areas as an initial symptom. This is followed by a loss of side vision, causing affected people to bump into objects. Loss of peripheral vison also makes it difficult for people to drive. People with advanced RP have either a very small area of central vision or may be totally blind.
The DNA within the cell forms the building block of the entire human body. It consists of ‘Nucleotides’ which are similar to the spellings in the alphabet series. Various combinations of these nucleotides form proteins, necessary for the functioning of the retina. Any change in these spellings is known as ’mutations’. These mutations then alter the functioning of the photoreceptors or RPE and cause genetic diseases of the retina.
RP is a genetic disease, caused by over 200 mutations, associated with the functioning of either the photoreceptors or the RPE.
With age and disease progression, many people with RP lose significant amount of peripheral vision leading to legal blindness. However, they may continue to retain central vision for many years. The severity is mostly based on the genetic mutation that the individual carries.
The progression of RP can be assessed by a clinical examination conducted by a retina specialist and noninvasive testing that includes fundus photos, optical coherence tomography and visual field examination.
Currently, there is no available treatment for most forms of RP. One form of RP, caused by mutations in the RPE65 gene only has been approved for use outside of India. It is called Luxturna and is injected under the retina by a surgical procedure. This is not yet available in India.
Stem cell treatment is not yet an approved therapy for treatment of RP. There have been multiple reports of people losing sight due to injections of so-called stem cells into the eye. It is certainly not recommended to take stem cell treatments without exercising caution.
RP is a genetic disease. Every individual has two copies of each gene, inherited from each parent. Almost all individuals carry mutations in one copy of many genes. The presence of the second normal copy in them prevents them from developing a disease. When two such people have a child, there is a 25% chance that each one may provide the mutated copy of the gene to the child. This child who now has one mutation from each parent at the same site of the gene (adding up to two mutations at the same spot) ends up with a disease, even when both his parents are clinically normal. While there are multiple ways that genetic diseases can occur, this is the commonest way that RP is inherited in families.
It is possible to identify the mutation an individual carries by a genetic testing. This involves obtaining a blood or a saliva sample from the affected patient and their family.
At Eyestem Research, we have grown the photoreceptor cells that are lost in RP through a repeatable protocol. Subsequently, we have injected these cells into special animal model of degenerating retina and proven that the injected animals maintain their vision compared to non-injected animals. Eyestem needs to repeat the same experiments in a larger set of animals to ensure the results are repeatable and predictable.
Once the above is done, we shall move to experiments to prove that our cells are safe as per the requirements and standards accepted by the Drugs Controller General of India.
Once we do that, we would be able to submit an application for starting a human trial in India. At this point, we anticipate such an application to be made in the last quarter of 2023.
Other than Dry AMD and RP, we are not looking to treat any other ophthalmic disease at this time.
The clinical trial is designed for specific end points and hence will have strict inclusion/exclusion criteria. While the clinical partners that we intend to work with will have their own network of patients, if we need more patients, a call for recruitment will be made at that time. It is important to remember that a clinical trial is not a guarantee for treatment but rather an attempt to understand the efficacy of a drug.
While we attempted to answer as many questions as we could, we are afraid we are not equipped to see patients across India. We will continue to release posts such as this for information but are not in a position to see individual patients. This is best done by a local retina specialist.
It will take anytime between 4-5 years before such a treatment is available. Each of these treatments has to go through rigorous, sequential clinical trials and regulatory approvals to prove that they indeed are efficacious and that their benefit to society justifies their approval. Unfortunately, due to the nature of scientific research, it is not possible to provide a date with absolute certainty but we at Eyestem are trying our best to get this done as fast as we can while adhering the regulatory laws of the land.
Most schools these days are fairly open to issues like these and we suggest a frank discussion between yourself, the school principal and your ophthalmologist. Sometimes small changes like ensuring the child isalways seated on the front bench and near a light makes a big difference. It is important to let the child be aware of his/her limitations since most kids are very resilient and find a way to adapt in ways that sometimes surpass adults.
We also ask that you work with low vision experts who can help devise a solution that is specific for your child. One such device that we can recommend is the Lumino developed by Forus Health. You can find more information on the device at the link https://www.cegr.org/lumino/. Please note that Eyestem hasno linkages- financial or otherwise- with Forus Health.
Regenerative medicine is at the cusp of a breakthrough globally and the same will happen in India as well. Our advice to patients is the following