Chest port for Brineura in CLN2 more stable than scalp-based device
No problems with access, infection seen with modified system
A new system that delivers Brineura (cerliponase alfa) into the brains of people with CLN2 disease, also known as late infantile Batten disease, via a port implanted in the chest provides a more stable and well-tolerated alternative to scalp-based infusions, a case series reports.
None of the seven patients who underwent the placement of this new system experienced problems with access, infection, or the need for revision since implantation.
“Our conversion of the traditional scalp port to a chest port was able to be performed with ease and has resulted in better quality of life for these patients, with no reported adverse reactions or complications since implantation,” the researchers wrote.
The case series, “Novel surgical approach for intraventricular cerliponase alfa enzyme replacement therapy via central venous access device (CVAD) port in neuronal ceroid lipofuscinosis type 2 (CLN2) disease,” was published in the journal Child’s Nervous System.
Scalp-based device associated with various complications
CLN2 disease is a genetic disease marked by a deficiency of the TPP1 enzyme, which normally clears out certain types of molecular waste inside cells. A lack of functional TPP1 leads to a toxic buildup of waste that damages cells and drives disease symptoms, including seizures, vision loss, and motor problems.
Brineura, by Biomarin Pharmaceutical, is designed to provide cells with a functional version of the TPP1 enzyme, allowing the clearance of cellular waste to slow disease progression. It’s administered via intracerebroventricular infusion, or directly into the cerebrospinal fluid (CSF) around a patient’s brain via a surgically implanted device in the skull.
Because Brineura is given every two weeks for life, and each infusion lasts four to five hours, treatment can be a burden for patients and families. Moreover, the device needs to be replaced after about four years, and its placement has been associated with various complications, including infections, surgical site swelling that prevents infusion, leakage, and catheter blockages.
Recently, an alternative infusion system was described that connects the catheter in the brain to a tube that travels inside the body to a port implanted under the skin on the front of the chest. With this system, the therapy is infused via the chest port, and then flows to the brain.
In this report, researchers describe seven patients who underwent this modified surgical approach to reduce the problems associated with prolonged scalp-based infusions.
New port system described in 7 patients, ages 3 to 24
The first case was an 11-year-old boy who was diagnosed with CLN2 at the age of 2 and underwent the standard skull implant to receive Brineura. However, over time, he began to experience difficulty with treatment, often requiring multiple needles to access the scalp reservoir. After about 80 infusions, he had a CSF leak. He then received the modified port system, which has been used more than 160 times without infection, device failure, or infusion issues.
The second patient, an 8-year-old girl, was diagnosed with CLN2 disease a few months before the placement of a chest access device at the age of 4. Before diagnosis, she developed normally until she began experiencing seizures, followed by several months of motor regression. She underwent chest port placement, which has since been accessed more than 100 times without complications.
In the third case, a 24-year-old man was diagnosed with atypical CLN2 disease at 18 years old. He presented more gradually with cognitive delays beginning at age 2, problems with coordination at age 5, dyslexia (a written language disorder) at 7, and a loss of body coordination (ataxia) at 14. He received the standard scalp placement but had subsequent access difficulties on multiple occasions, developed an infection, and showed disease progression while on Brineura. Since receiving the new system, his chest port has been accessed 140 times without problems.
The fourth case was a 19-year-old woman and sibling of the third patient, who also had a diagnosis of atypical CLN2 and had received the standard scalp device placement. In infancy, she had failed to thrive, and her development was delayed. Her speech and motor development were also delayed, with her first words and walking occurring at around 15 months. Before treatment, she did not have any seizures, vision loss, or motor/cognitive regression. While she had no access problems or complications related to the scalp implant, she switched to a chest port for easier access, which has been used 110 times without complications.
Patient five, a 3-year-old boy and sibling of the third and fourth patients, was diagnosed with atypical CLN2 disease after his brother tested positive for the disease. He presented with speech delays at just before 2 years of age. Since placement of the chest port, he’s had no problems with the procedure or access, with 40 port infusions without complications so far.
In the sixth case, a 7-year-old boy with atypical CLN2 disease had developmental delays at 18 months of age, and delayed speech and absence seizures at age 3. Since the placement of the chest port system, there have been no access problems, his symptoms have remained controlled, and he has tolerated the treatment well. His chest port has been used 41 times without issues.
Lastly, the seventh patient, a 5-year-old boy with CLN2 disease, presented with seizures, speech delays, and tics at age 3. Since the chest port system was placed, it’s been accessed 30 times without complications.
“This approach has the potential to reduce rates of device failure and infection while making the process of prolonged [Brineura] infusions easier and safer for patients, families, and providers,” the researchers concluded.
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