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Batten Disease: Precision Therapeutics Neuro-Interventional Program

What is Batten Disease?

Batten disease, also known as neuronal ceroid lipofuscinosis (NCL), is a rare group of inherited neurodegenerative disorders that primarily affect children. These disorders are characterized by the accumulation of lipopigments (lipofuscin) in various tissues of the body, including the brain, which results in progressive neurological deterioration.

At Rady Children’s Hospital, we are now providing intraventricular enzyme replacement gene therapy infusion treatments for patients with Batten Disease. This groundbreaking treatment is designed to slow down the progression of the disease in individuals suffering from this neurodegenerative disorder. As the third center in California to offer this program, we aim to expand access to care throughout the state and help alleviate the travel burden faced by families and affected children who require these bi-weekly infusions.

What Causes Batten Disease?

Batten disease, a type of neuronal ceroid lipofuscinosis (NCL), is a genetic disorder impacting brain functionality due to impaired waste disposal in cells. This leads to waste accumulation, hindering cell function and causing symptoms like seizures, vision loss, and cognitive decline. There are different forms of Batten disease with varying severity and onset.

Mutations in genes related to waste breakdown cause lipopigment buildup, particularly affecting the brain and retina. Although Batten disease is rare, its progression can lead to cell death. Diagnosis often involves genetic testing to identify specific mutations.

While there’s no cure, treatments aim to manage symptoms and enhance quality of life. Supportive care measures like therapy address motor and communication difficulties. Gene therapy shows promise in correcting genetic defects and halting disease progression, with ongoing clinical trials offering hope for future treatments.

Organizations like the Batten Disease Foundation provide resources and support for affected individuals and families, aiding in raising awareness and funding research. Research efforts focus on understanding underlying genetic mutations and developing effective therapies.

In recent years, gene therapy has emerged as a promising treatment avenue for Batten disease. This approach involves introducing healthy copies of the mutated gene into the affected cells to correct the underlying genetic defect and potentially halt the disease’s progression. Clinical trials investigating gene therapy for Batten disease are currently underway, offering hope for future therapeutic options.

What Are the Symptoms of Batten Disease?

During the progression of Batten disease, symptoms can be different in each child. During the progression of Batten disease, the symptoms exhibited by affected children can vary considerably. Each child may experience a unique combination of symptoms that manifest as the disease advances. These symptoms serve as indicators for the onset and progression of the disease, and can significantly impact the physical, cognitive, and behavioral aspects of a child’s life.

The symptoms may include:

  • Seizures (epilepsy) – One of the most commonly observed symptoms of Batten disease is seizures, also known as epilepsy. These episodes of abnormal electrical activity in the brain can range from mild to severe and can manifest as various types of seizures, including generalized tonic-clonic seizures or absence seizures.
  • Speech delays – Another symptom frequently associated with Batten disease is speech delays. As the disease progresses, affected children may experience difficulties with expressive and receptive language skills. This can result in challenges in articulating words, forming sentences, or comprehending verbal communication.
  • Unsteady walking (ataxia) – Unsteady walking, medically referred to as ataxia, is another symptom that can develop during the progression of Batten disease. Ataxia is characterized by impaired muscle coordination, leading to difficulties in maintaining balance and executing precise movements. The gradual loss of motor skills, including the ability to walk, talk, and communicate, further contributes to the debilitating nature of this disease.
  • Loss of motor skills – The ability to walk, talk, and communicate
  • Cognitive decline – Cognitive abilities gradually decline in children with Batten disease. As the disease affects the central nervous system, it impairs various cognitive functions, including attention, memory, and problem-solving skills. Children may struggle with learning new information, retaining previously acquired knowledge, and processing complex tasks./
  • Visual impairment/blindness – Visual impairment or blindness is a significant consequence of Batten disease. The degeneration of cells in the retina, the light-sensitive tissue at the back of the eye, leads to progressive vision loss. Initially, affected children may experience difficulty with peripheral vision, reduced visual acuity, and increased sensitivity to light. Eventually, complete blindness can occur, further impacting their independence and overall quality of life.
  • Jerking movement of the muscles (myoclonus) – Myoclonus, characterized by jerking movements of the muscles, is another common symptom in Batten disease. These sudden, involuntary muscle contractions can affect various parts of the body and occur randomly. Myoclonus can further contribute to difficulties with mobility, coordination, and balance.
  • Dementia – Dementia, a progressive decline in cognitive function, is often observed in individuals with Batten disease. This cognitive decline affects memory, thinking abilities, and behavior, leading to significant challenges in daily living. The gradual loss of cognitive function can have a profound impact on a child’s overall well-being and their ability to engage in meaningful activities.
  • Personality and behavior changes – One of the distressing aspects of Batten disease is the emergence of personality and behavior changes in affected children. As the disease progresses, children may undergo shifts in their temperament, exhibiting irritability, aggression, impulsivity, and emotional instability. These behavioral changes can be challenging for both the affected child and their caregivers to manage.
  • Psychiatric symptoms, such as aggression – In some cases, Batten disease may also present psychiatric symptoms. Aggression, anxiety, depression, and other mental health issues can arise as the disease affects various regions of the brain. Proper management and support for these psychiatric symptoms are vital to ensuring the holistic well-being of affected children.
  • Extrapyramidal symptoms – This includes spasms, restlessness, rigidity, tremors, or jerky movements, may also manifest in individuals with Batten disease. These involuntary movements are a result of dysfunction in the extrapyramidal system, a network of nerves that modulates motor control and coordination. These symptoms can further exacerbate difficulties with mobility and motor skills in affected children.

Overall, Batten disease encompasses a broad range of symptoms that affect multiple aspects of a child’s life. By understanding the diverse manifestations of the disease, healthcare professionals, researchers, and caregivers can work collaboratively in providing comprehensive care, support, and interventions to enhance the quality of life for those affected by Batten disease.

What Are the Types of Batten Disease?

Batten disease manifests in various forms, each linked to specific genetic mutations. The main types of Batten disease are as follows:

  1. CLN1 (Infantile Batten Disease): This variant usually appears between 6 months and 2 years of age. Symptoms commonly involve rapid vision impairment, seizures, motor regression, and intellectual disability.
  2. CLN2 (Late Infantile Batten Disease): The onset of this form typically occurs between the ages of 2 and 4. Language difficulties, motor impairments, seizures, and progressive cognitive decline are common symptoms.
  3. CLN3 (Juvenile Batten Disease): Juvenile Batten Disease is typically recognized between the ages of 4 and 10. Symptoms often include vision loss, changes in personality and behavior, seizures, as well as a decline in cognitive and motor function.
  4. CLN5, CLN6, CLN7, CLN8, etc.: Other types of Batten disease exist, associated with diverse genetic mutations. Each variant has its own distinctive age of onset and characteristic symptoms.

Treatment Process for Batten Disease at Rady Children’s Hospital

At Rady Children’s Hospital, our comprehensive program for treating Batten disease encompasses a targeted approach aimed at slowing down the progression of this neurodegenerative disorder. Our treatment protocol involves a series of specialized steps designed to deliver precise therapeutics and support to affected children and their families.

Targeted Enzyme Replacement
One of the cornerstones of our treatment approach involves targeted enzyme replacement therapy administered via Ommaya intraventricular reservoir. This procedure is performed by our team biweekly, ensuring consistent and effective delivery of enzymes directly to the affected areas in the brain.

Ambulatory Setting Delivery
Our treatment program is conducted in an ambulatory setting, specifically through our Infusion Center. Unlike other institutions, we do not require admissions or hospitalization, providing a more convenient and accessible option for patients and their families.

Streamlined Process
We have developed a streamlined process to facilitate the delivery of enzyme replacement therapy, including the handling of high-cost pharmacy processing of frozen enzymes. Patients arrive at our facility at their scheduled time, where enzymatic thawing occurs, and the therapy is delivered promptly.

Insurance Coverage
We understand the financial concerns associated with high-cost medications, which is why our team ensures comprehensive insurance coverage for drug costs. We handle prior authorizations and work with various insurance providers, including CCS and private insurers, to ensure patients receive the necessary coverage.

Efficient Treatment Sessions
Our goal is to provide efficient and timely treatment sessions for all families. Patients receive their doses on the same day of their visit and typically leave our facility by 2 pm, minimizing disruption to their daily routines.

Rapid Whole Genomic Sequencing
For patients presenting with atypical symptoms or older onset of symptoms, we offer rapid whole genomic sequencing for timely and accurate diagnosis. Powered by Rady Children’s Institute for Genomic Medicine, this approach allows for precision therapeutics based on genetic mutations, facilitating early intervention to prevent disease progression.

Early diagnosis and intervention are crucial in managing Batten disease, a rapidly progressive neurodegenerative disorder in children. Our multidisciplinary team of medical professionals works with members of Pediatric Neurology and other programs to provide advanced therapies and personalized care to improve outcomes and enhance the quality of life for our pediatric patients.

Our Team

Olivia Kim-McManus, M.D., is a child neurologist and epileptologist at Rady Children’s Hospital-San Diego, Neurology Section Vice Chief, Associate Clinical Professor of Neurosciences at UC San Diego School of Medicine Department of Neurosciences, and clinical investigator at Rady Children’s Institute for Genomic Medicine. Dr. Kim-McManus specializes in treating infants, children and adolescents with pediatric neurological diseases including neurological conditions related to brain malformations, underlying genetic etiologies, intellectual disabilities, and neurodevelopmental disorders of childhood. Her primary expertise and research activities include clinical neurophysiology, and epilepsy surgery (i.e. invasive intracranial electroencephalography monitoring and intraoperative electrocorticography), and epilepsy genetics, in particular, investigational targeted cell and gene-based therapeutics for rare disease including personalized antisense oligonucleotide therapy for developmental epileptic encephalopathies.

David Gonda, M.D., is the director of Epilepsy Surgery at Rady Children’s Hospital-San Diego and an assistant clinical professor of neurosurgery at UC San Diego School of Medicine. Dr. Gonda’s clinical areas of expertise are epilepsy surgery, MRI laser thermal ablation surgery, pediatric spine abnormalities, and craniovertebral junction abnormalities. His research area of expertise is minimally invasive epilepsy surgery. Dr. Gonda has specialized training in utilizing a new robotic assist device called ROSA, which Rady Children’s has obtained. He is using the robot for epilepsy surgery and other neurological procedures.

Jong Rho, M.D., Dr. Rho is the division chief of neurology at Rady Children’s Hospital-San Diego and a professor of neurosciences and pediatrics at UC San Diego School of Medicine. His clinical expertise is in general pediatric neurology and pediatric epilepsy, with an emphasis on pharmacological therapies and metabolic approaches toward epilepsy treatment, such as the ketogenic diet. His main research interests for patients, including at Rady Children’s Hospital-San Diego, are the mechanisms underlying the anti-seizure and neuroprotective effects of the ketogenic diet and its clinical variants.

Contact Us

For inquiries or referrals to the Pediatric Batten Disease Program at Rady Children’s Hospital, please feel free to reach out to us:
Toll-free: 800-788-9029
Phone: 858-966-4096
E-mail: refsvc@rchsd.org