- Batten disease is the name for a collection of rare, inherited, and fatal diseases that often begin in childhood.
- One form, called CLN3 disease, is characterized by progressive loss of vision at the age of 4 to 7 years, followed by learning and behavior problems, cognitive decline, and seizures.
- The genetic changes underlying different types of Batten disease are well established, but their cause is less well understood.
- New study reveals how the genetic mutation responsible for CLN3 disease can damage photoreceptors in the retina.
In Latte disease, which involves progressive degeneration of the nervous system and usually begins in childhood, genetic mutations interfere with the ability of cells to recycle their wastes.
Batten disease is not a single condition but a collection of rare and fatal disorders that are officially known as neuronal ceroid lipofuscinosis. They share some characteristics but differ in severity and the age at which symptoms first appear.
The ‘juvenile onset’ form of the disease, called CLN3 disease, involves vision loss at the age of 4 to 7 years, followed by worsening learning and behavior problems, dementia, and impairments. convulsions around 10 years old.
Adolescents with CLN3 disease develop movement and language problems. Most people with the disease die between the ages of 15 and 30.
CLN3 is a protein in the membranes that surround the various compartments inside cells. Researchers aren’t sure what the protein typically does, but it appears to be involved in molecular recycling and waste disposal.
In someone with CLN3 disease, a defective version of the protein damages photosensitive cells in the retina, eventually leading to blindness.
However, the underlying cause has not been clear in postmortem studies because the damage is so extensive by the time the patients have died.
A new study by scientists at the University of Rochester, New York, suggests how the protein can trigger the process.
âIt is important to understand how vision loss is triggered in this disease, what is primary and what is secondary, and this will allow us to develop new therapeutic strategies,â says Ruchira Singh, Ph.D., associate professor in the Department of Ophthalmology and the Center for Visual Sciences of the university and lead author of the study.
The research was published in the journal
One problem for scientists trying to understand the causes of sight loss in children with CLN3 disease is the lack of an appropriate animal model of the disease.
Dr Singh and his team overcame this difficulty by creating pluripotent stem cells from the skin cells of patients and their unaffected relatives.
Pluripotent stem cells have the remarkable ability to develop into any type of cell in the body.
Then the scientists turned these stem cells into a type of cell that forms a layer of tissue in the eye called the
The RPE has a wide range of support functions that are vital for photoreceptor cells in the retina.
One function is to continually “eat away” or “swallow up” discarded waste.
In RPE cells derived from healthy individuals, the researchers found the CLN3 protein in hair-like projections called microvilli. These help to engulf and eliminate the outer segments of the photoreceptors.
Patients’ RPE cells, however, had fewer microvilli and were less good at ingesting these outer segments, which may explain the progressive loss of sight that occurs in CLN3 disease.
Above all, the researchers were able to correct the problems in these cells. They used a virus to carry a regular version of the CLN3 gene in the nuclei of cells, restoring their ability to ingest the outer segments of photoreceptors.
Research on this rare but devastating disease remains at a very basic stage.
However, Dr Singh hopes that a better understanding of RPE cell dysfunction in people with the disease will eventually lead to effective therapies.
She notes that these could include gene therapy, cell transplantation or drug interventions.