Batten disease, a group of fatal genetic disorders
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There are small bodies in our cells called lysosomes. Their task is to clean the cell: they break down compounds to smaller parts that can be thrown out of the cell or recycled.
In a case of Batten disease, genes don't provides information normal genes do, lysosomes don't work correctly, and that causes cell waste to build up. It is obvious that build up of waste elements in a cell can't be good.
And indeed, it's very bad. Children with Batten disease have very short life expectancy and in some cases patients live to their thirties. Batten disease can develop in adults but then symptoms are usually mild and life expectancy is not shorter than usual.
There are 13 typs of Batten disease, depending on gene that causes the disease. Each gene is called CLN (ceroid lipofuscinosis, neuronal), so Batten disease type are CLN1, CLN2, and so on.
Batten disease, or Neuronal Ceroid Lipofuscinosis (NCL), has 13 known forms. Progressions of the different forms of the disease vary (the phenotype) based on the type of genetic mutation (the genotype) and other factors. Each form is classified by the gene that causes the disorder. Each gene is called CLN (ceroid lipofuscinosis, neuronal) and given a different number designation as its subtype.
Lets' go briefly through them.
CLN1 disease, infantile onset
Symptoms appear before age 1 and the disease progress rapidly. Standing, walking, and talking can't be learned or are lost after being learned. Then there are often seizures by age 2 and blindness. By age 3 children may be dependent on their caregivers and some may need a feeding tube. Most die in early to mid-childhood.
CLN1 disease, juvenile onset
Some children develop the disease around age 5 or 6 and have slower disease progression. They may live into teenage years or they have no symptoms until adolescence and may live into adulthood.
CLN2 disease, late-infantile onset
Developmental delay begins around the end of age 2. After that there are seizures, a gradually loss of walk and speak abilities. Involuntary jerks in muscle s begin around age 4-5. By age 6 most they are completely dependent on their caregivers, and many will require a feeding tube. Most die between the ages of 6–12 years.
CLN2 disease, later-onset
Some children develop the disease around age 6 or 7 and have slower disease progression. Loss of coordination may be the initial symptom. They may live into their teenage years.
CLN3 disease, juvenile onset (ages 4-7)
Rapidly progressive vision loss begins between ages 4 and 7. Then there are learning and behavior problems, dementia, and seizures around age 10. In the teenage years, symptoms are slow movement, stiffness, loss of balance, difficulties with speech and language. Later, children and teenagers become dependent on their caregivers. Most die between the ages of 15 and 30.
CLN4 disease, adult onset
This form typically begins around age 30 and causes problems with movement and early dementia. The age of death varies among affected individuals.
CLN5 disease, variant late-infantile onset
Children progress normally for the first few years before losing skills and behavior problems. Seizures and jerks begin between ages 6 and 13. Vision deteriorates and is eventually lost and there are learning disabilities, problems with concentration and memory, and some may need a feeding tube. Most live into late childhood or teenage years.
CLN6, variant late-infantile onset
Symptoms vary among children, but typically start after the first few years and include developmental delay, changes in behavior, and seizures. They eventually lose skills for walking, playing, and speech, there are jerks, problems with sleep, and vision loss. Most die during late childhood or in their early teenage years.
CLN6, adult onset
This form shows signs in early adulthood that include epilepsy, lack of balance or coordination, and then there is a slow but progressive cognitive decline.
CLN7, variant late-infantile onset
Developmental delays begin after a few years in which a child appears to be normal. Children develop epilepsy between the ages of 3 and 7, and then there are problems sleeping and jerks. Then they begin to lose the ability to walk, play, and speak, with a rapid advancement of symptoms between the ages of 9 and 11. Most live until their late childhood or teenage years.
CLN8 disease with Epilepsy with Progressive Mental Retardation (EPMR)
Symptoms begin between ages 5 and 10 and include seizures, cognitive decline, and behavioral changes. Seizures become significant after adolescence and loss of speech occurs in some patients. They can live into adulthood. A very rare form of CLN8 is called Northern Epilepsy syndrome because it occurs in some families in Finland.
CLN8 disease, late-variant onset
Affected children begin showing symptoms between ages 2 and 7, which include loss of vision, cognitive problems, unsteadiness, myoclonic jerks, and behavioral changes. Patients develop treatment-resistant epilepsy and lose cognitive skills by age 10. Many lose the ability to walk or stand on their own. Some have lived into their second decade of life.
This is a very rare disease. It is seen soon after birth, although it can occur later in childhood or adulthood. Some children have microcephaly. Seizures may occur before birth and after birth babies may have seizures that can't be treated, problems with breathing that can lead to respiratory failure, and there is obstructive sleep apnea. Babies may die shortly after birth or within the first weeks of life.
A late-infantile form features a later onset of symptoms and slower disease progression. Children develop seizures and problems with vision, balance, and intellectual skills. They may have problems coordinating muscle movement and trouble with walking. They often die in early childhood.
So, in short: Symptoms may start before the first birthday and they include seizures, vision loss, abnormal movements, and loss of skills they previously learned.
Later, more symptoms arrive: personality change, learning difficulties, anxiety, lack of concentration, difficulty sleeping, and involuntary movements. After that it goes worse: worse seizures, dementia, loss of motor skills and speech.
In the end, children are wheelchair bound, blind, unable to communicate, and lose all cognitive functions.
We don't know how many people have Batten disease but it is believed that 1 in 12,500 people carries two genese that cause it.
Most diagnoses of Batten disease are made by genetic testing, but there are also measurement of enzyme activity, electroencephalograms and computed tomography that can confirm or deny it really is Batten disease.
There is no cure for Batten disease but a treatment for CLN has been approved by the U.S. Food and Drug Administration (FDA).
The University of Rochester Medical Center (URMC) will serve as the lead study site in the U.S. for an experimental treatment for CLN5 Batten disease.
Neurogene’s NGN-101 was cleared by the Food and Drug Administration to begin clinical trials and has received Orphan Drug Designation by the U.S. and European regulatory agencies.
The clinical trial will evaluate a single intraventricular dose delivered directly into cerebrospinal fluid in the brain. The treatment NGN-101 uses a virus to deliver a healthy version of CLN5 gene directly to the central nervous system. Animal studies have shown that the treatment has the potential to halt the key features of disease progression, including vision, motor, cognitive, and behavioral declines. ■