Brineura (cerliponase alfa) stabilized the progression of neuronal ceroid lipofuscinosis type 2 (CLN2) – a type of Latte disease – in a small group of people in Colombia, including those whose atypical onset occurs later in childhood.
These results come from a small series of cases, “Real efficacy of cerliponase alfa in classical and atypical patients. A series of cases, â€Which was published in the journal Molecular Genetics and Metabolism Reports.
Due to mutations in the TPP1 gene, which causes TPP1 enzyme deficiency, loss of muscle coordination (ataxia) and seizures are the first symptoms of CLN2, also called late infantile Batten disease, which usually appear between the ages of 2 and 4 years.
In some cases, called atypical CLN2, symptoms appear later in childhood and include seizures, language difficulties, and behavioral problems.
Brineura is an enzyme replacement therapy (ERT) designed to replace the missing TPP1 enzyme, aimed at slowing down ataxia and other symptoms.
This study, conducted by researchers based at the Fundación Hospital Pediátrico la Misericordia (HOMI) in Colombia, described the presentation of CLN2 in eight patients, as well as the impact of Brineura on the course and progression of the disease for two years.
The team collected data on disease onset and treatment from medical records, and follow-up assessments included the CLN2 Clinical Rating Scale (Motor, Language), Weill Cornell Scale ( swallowing, walking, motor function and language) and the Hamburg scale (motor, language and visual). With all scales, higher scores indicate better results.
Among those selected, typical CLN2 occurred in three participants, with a median age of onset of 52 months (4.3 years), a median time from symptom onset to diagnosis of six months, between diagnosis and the start of treatment for four months and treatment for 16 months. time.
In contrast, five were patients with atypical CLN2, with a median age of onset of 139 months (11.6 years), a median time from symptom onset to diagnosis of two years, time from diagnosis and the start of treatment for 13 months and treatment for eight months. time. A new TPP mutation was found in two atypical patients.
Two atypical patients were siblings, one diagnosed as asymptomatic due to the elder’s history.
On the first visit to the clinic, seizures were seen in seven of the eight patients, six with language difficulties, four with developmental problems and three with ataxia and movement disorders. Six participants had an affected parent.
Prior to ERT, three of eight patients developed ataxia, three developed movement disorders, and two regressed in their language development.
Of the three participants with typical CLN2, two developed ataxia, two developed movement disorders, and two patients experienced developmental regression, and all had eye problems.
Of the five with atypical features, one developed ataxia, one movement disorder, and one vision impairment, while one patient remained asymptomatic. All patients had undetectable or below normal range TPP1 enzyme activity.
Anticonvulsant drugs prior to ERT included valproic acid (6 of 8 patients), levetiracetam (2 of 8), clobazam (3 of 8), oxcarbazepine (1 of 8), and lamotrigine (1 of 8).
All patients received 300 mg of Brineura infused directly into the fluid surrounding the brain every 15 days. After ERT, there was a reduction in the use of valproic acid in atypical patients (3 out of 5 patients vs. 1 in 5) but an increase in the use of levetiracetam (1 in 5 vs. 2 in 5) and clobazam (none vs. 1 in 5). For those with typical characteristics, the drugs remained constant.
Function scores for all assessments analyzed before and after treatment did not show statistically significant differences in typical and atypical participants.
However, there was no evidence of disease progression during follow-up, as defined by a colon drop in the CLN2, Hamburg, and Weill Cornell scales for typical and atypical patients. No serious adverse side effects were reported for all participants.
“These data support stabilization of disease progression in both atypical and classical phenotypes [characteristics], with an adequate safety profile that was similar to that reported in other studies, â€the researchers wrote.
“Our study highlights the importance of early diagnosis and rapid initiation of treatment, which is a feasible treatment, well tolerated by patients and accepted by caregivers in this country, generating a positive impact on quality. life of patients with CLN2 and the course of the disease, â€they added.
