Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease

CLN2 disease is a predominantly late infantile form of neuronal ceroid lipofuscinosis and one
of the many genetic isoforms of Batten disease. Mutations in the CLN2 gene are characterized
by deficient lysosomal serine protease TPP1, an enzyme that metabolizes intracellular
lysosomal storage materials. Accumulations of intracellular deposits occur over time and in
many organs of individuals with CLN2 disease and lead to neurodegeneration and, eventually,
death. CLN2 disease is an extremely rare genetic disease affecting around 1 per 200,000 live
births. Symptoms emerge early in life typically between the ages of 2 and 4 years of age and
include seizures, as well as loss of motor, language, and vision functioning. Development
further declines in early childhood and by age 6 years, children with CLN2 are often unable
to walk or sit unsupported and become blind. The progression of the disease is rapid with
death typically occurring in mid-childhood between the ages of 10 and 15 years of age.

Recently, enzyme replacement therapy (ERT), cerliponase alfa, which is a recombinant form of
human TPPI, was the first FDA-approved treatment to slow the progression of motor decline in
children with CLN2. Cerliponase alfa is expected to restore TPP1 enzyme activity in the brain
and alter neurodegeneration and disease progression. Animal models suggest promising
treatment outcomes as cerliponase alfa significantly delayed the onset of clinical signs,
preserved motor and cognitive function, and prolonged life. Initial results from a clinical
trial further demonstrated that patients receiving cerliponase alfa had less motor declines,
as measured by the CLN2 Clinical Rating Scale, compared to a natural history cohort. Despite
these promising results, little is known about the trajectory of other developmental domains,
including language, social-emotional, and adaptive functioning of children receiving
cerliponase alfa. Likewise, the developmental trajectory of untreated patients with CLN2 is
not well understood. Therefore, it is important to understand developmental outcomes and the
progression of CLN2 in a natural history cohort in order to compare the effectiveness of
treatment outcomes.

Inclusion Criteria:

- Patients that have a TPP1 enzyme deficiency

- Patients have confirmed molecular diagnosis of pathogenic variants in the TPP1 gene

- Patients that are enrolled in post-marketing studies will be allowed to enroll into
the current study

Exclusion Criteria:

- Patients without a diagnosis of CLN2 and deficiency of TPP1

- Patients that are currently enrolled as part of a larger multi-center clinical trial