Batten Disease

What Causes Batten Disease?

NCLs are caused by mutations in genes responsible for making proteins that are crucial for brain cell function. Specifically, the proteins assist in the function of cell structures called lysosomes, which break down cell waste products. The NCL-causing gene mutations interfere with the production of these proteins, so lysosomes can’t effectively remove the waste products. As the harmful wastes build up, the cells don’t function properly and are eventually damaged.

Mutations in different genes cause different forms of the disease. The variations generally result in different times for the onset of symptoms, and they may also influence the severity and progression rate of the symptoms.

Is Batten Disease Hereditary?

Most forms of Batten disease are autosomal recessive, meaning a child must inherit a copy of the mutated disease-causing gene from both their mother and their father. The child inherits one copy of each gene from each parent, and if they inherit a mutated copy and a normal copy, the disease won’t develop. The disease only occurs when two mutated copies are inherited.

The disease’s recessive trait means that a person can possess one copy of the mutated gene without developing symptoms of the disease. In this case, the person is a carrier of the disease. If they have a child with another carrier, that child will have a 25% chance of developing Batten disease and a 50% chance of being a carrier themselves.

In some cases, adult-onset NCL can be autosomal dominant. In this case, the disease will develop even if the individual has only inherited one copy of the mutated gene.

How is Batten Disease Detected?

The earliest signs of Batten disease are usually seizures and/or vision loss. Less obvious early signs include slow motor and cognitive development, clumsiness, and changes in behavior or personality.

There is no cure for Batten disease or any treatment that will reverse the symptoms, so early detection will not improve the prognosis. However, an early diagnosis can help families come to terms with the disease and improve the child’s quality of life as the disease progresses.

How is Batten Disease Diagnosed?

Batten disease is sometimes misdiagnosed in its early stages; epilepsy, seizure disorders, autism, and pervasive developmental disorder (PDD) often being suspected. However, several different tests can help to confirm the presence of NCL.

• Genetic testing. These tests look for the specific gene mutations that cause NCLs, and they are the tool most commonly used to diagnose Batten disease. Testing for NCLs is now widely done when diagnosticians conduct genetic testing for epilepsy. These tests can also identify a carrier of the disease-causing gene even when symptoms aren’t present.
• Blood or urine tests. These tests can identify chemicals or abnormal white blood cells that are characteristic of some types of NCL.
• Enzyme tests. These tests look for the activity of chemicals within cells that are common in certain types of NCL.
• Tissue samples. Microscopic examination of skin cells or other tissues can show the buildup of lipofuscin, a chemical accumulation that indicates NCLs.
• Electroencephalogram (EEG) and imaging exams. These tests can identify patterns of brain activity or brain structure that can suggest Batten disease is present.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How is Batten Disease Treated?

No treatment will cure Batten disease or improve its symptoms.

In 2017, the Food and Drug Administration approved a medication that has shown the ability to slow or stop the progression of symptoms in one specific type of NCL called CLN2, a late-onset disease type. The drug, called cerliponase alfa, replaces a crucial enzyme whose production is inhibited by the disease-causing gene. The medication is only effective in treating CLN2 and can’t treat other forms of the disease.

Medications such as antiseizure drugs are sometimes used to control Batten disease symptoms, and physical and occupational therapies may help improve the child’s quality of life as long as possible.

How Does Batten Disease Progress?

Children often appear to be healthy before the first symptoms of Batten disease appear. Once symptoms begin, they become progressively worse until motor and cognitive function are severely impaired. Eventually, sufferers will entirely lose the ability to see, walk, and communicate.

Progressive symptoms include:

• Seizures
• Vision impairment and loss
• Abnormal, jerky movements
• Personality or behavior changes
• Confusion or trouble concentrating
• Learning disabilities
• Trouble walking
• Loss of motor and/or cognitive skills that the child had previously acquired
• Sleep disruption
• Anxiety or depression
• Dementia
• Loss of the ability to walk or speak
• Total loss of cognitive function

How is Batten Disease Prevented?

When a child inherits the disease-causing gene mutations from both parents, there is no way to prevent the disease from developing. In the dominant variant of adult-onset NCL, even a single copy of the mutated gene will inevitably cause the disease.

If you have a family history of the disease, there is a chance that you are carrying a copy of the gene mutation and could pass the mutation on to your children. Genetic testing can confirm whether or not you are a carrier, and a genetic counselor can help you assess the risk of passing on the disease.

Batten Disease Caregiver Tips

A diagnosis of Batten disease is devastating for any parent. However, you can do some things to help your child and your family live with the illness and treasure the time you have together.

• Be a fierce advocate for your child. With the proper support and resources, you can help your child to have the best possible life for as long as possible. But you’ll likely have to push insurers, healthcare providers, and educators to give you everything you need. Mustering the strength to be a persistent voice for your child isn’t easy, but you will be glad that you never stopped fighting.
• Don’t repress your grief. Acknowledging and accepting your loss doesn’t mean that you’ve given up. When you allow yourself to move through the process of grieving, you’ll be better able to appreciate the beautiful moments you still have with your child.
• Don’t try to cope by yourself. NCLs are rare diseases, and you might feel isolated when your child is diagnosed. But the support of people who understand what you’re going through is invaluable as you live with the disease. Online resources can help you find support groups, information, and news about Batten disease.

Batten Disease Brain Science

Researchers are working on learning more about Batten disease to develop effective treatments or perhaps even cure the disease. Because different forms of NCL are caused by different gene mutations with different chemical effects, many of the treatments and therapies pursued by scientists are meant to treat only one form of the disease.

Current areas of research include:

• Gene therapies. These therapies involve introducing a replacement gene into brain cells, theorizing that the properly functioning gene will counter the mutated gene’s effects in NCL patients. The replacement genes are delivered by attaching them to a harmless virus that introduces the gene into cells as directed by scientists. One project has combined gene therapy and bone marrow transplants as a possible treatment for infantile NCL.
• Molecular drugs. These drugs work by introducing chemical molecules that may help the cells eliminate or recycle the waste products that cause Batten disease symptoms. Studies are pursuing the possible use of NtBuHA and lanthionine ketamine to treat the CLN1 form of the disease.
• Glutamate regulation. Another project is studying the way that the amino acid glutamate is recycled in brain cells. An excess of glutamate has been found in patients’ brain cells with the CLN3 form of the disease, and the chemical may be responsible for the symptom-causing cell damage. The project is attempting to develop chemical therapies that may help cells regulate and recycle glutamate.

Batten Disease Research

Title: Investigations of Juvenile Neuronal Ceroid Lipofuscinosis

Stage: Recruiting

Principal investigator: An N. Dang Do, MD 

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Bethesda, MD

Juvenile Neuronal Ceroid Lipofuscinosis (Batten Disease, CLN3) is a recessive, fatal, lysosomal storage disease that results in progressive neurodegeneration. In aggregate, the 13 disorders of neuronal ceroid lipofuscinosis are considered the most common neurodegenerative disorders in children, with incidence estimates ranging from 1/12,500 to 1/100,000 in European and USA populations. Neurological symptoms of CLN3 typically manifest between 4 and 7 years of age. The initial clinical presentation is progressive vision loss and cognitive impairment, followed by insidious progression of motor dysfunction and onset of seizures. Affected individuals generally succumb to the disease in young adulthood. There is no effective treatment for CLN3. A major impediment to the testing of potential therapeutic interventions is the lack of well-defined outcome measures. The purpose of this protocol is to obtain both baseline and rate of progression data on clinical and biochemical markers that may later be used as an outcome measure in a clinical trial, and to establish a biorepository of samples from CLN3 participants. For comparisons, focused clinical data and relevant evaluations and biospecimens will also be collected from individuals with Neuronal Ceroids Lipofuscinosis (NCL) of other types and also from family members of all affected individuals.

Title: Clinical and Neuropsychological Investigations in Batten Disease

Stage: Recruiting

Principal investigator: Jonathan W Mink, MD PhD

University of Rochester

Rochester, NY 

Batten Disease is an inherited disorder that causes progressive cognitive and behavioral decline in children. There have been no systematic clinical studies of Batten Disease using standardized rating instruments with known inter-rater reliability and validity.

The Batten Study Group developed the Unified Batten Disease Rating Scale (UBDRS), a clinical rating instrument used to assess individuals’ motor, behavioral, and functional capabilities with Batten disease. Using the UBDRS, study investigators will evaluate participants approximately every year to track disease progression. The UBDRS is the primary natural history tool, but the study also includes neuropsychological assessment, adaptive function, quality of life measures, and other measures to assess the impact of Batten Disease. Participants will be examined at the University of Rochester Batten Center, Batten Disease Support and Research Association annual meeting, or remotely via tele-video. Information related to racial and ethnic background, medical history, symptoms, medications, and diagnostic testing will be collected.

Title: UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells (DUOC-01)

Stage: Recruiting

Principal investigator:  Joanne Kurtzberg, MD

Duke University Medical Center

Durham, NC

The inherited metabolic disorders (IMD) are a heterogeneous group of genetic diseases, most of which involve a single gene mutation resulting in an enzyme defect. In the majority of cases, the enzyme defect leads to the accumulation of substrates that are toxic and/or interfere with normal cellular function. Often, patients may appear normal at birth but during infancy begin to exhibit disease manifestations, frequently including progressive neurological deterioration due to absent or abnormal brain myelination. The ultimate result is death in later infancy or childhood.

Currently, the only effective therapy to halt the neurologic progression of the disease is allogeneic hematopoietic stem cell transplantation (HSCT), which serves as a permanent cellular ERT source. However, one barrier to the success of this therapy is delayed engraftment of donor cells in the CNS when administered through the intravenous route, which is associated with ongoing disease progression over 2-4 months before stabilization. The engraftment of donor cells in a patient with an IMD provides a constant source of enzyme replacement, thereby slowing or halting the progression of the disease.

This study will evaluate the safety of a potential new treatment for patients with certain IMDs known to benefit from HSCT using allogeneic UCB donor cells. The new intervention, intrathecal administration of UCB-derived oligodendrocyte-like cells (DUOC-01), will serve as an adjunctive therapy to a standard UCB transplant. This therapy aims to accelerate delivery of donor cells to the CNS, thereby bridging the gap between systemic transplant and engraftment of cells in the CNS and preventing disease progression. The DUOC-01 cells and cells used for HSCT will be derived from the same UCB donor unit.