Scores from the Motor domain of the scale range from 3 (grossly normal) to 0 (profoundly impaired).The U.S. Food and Drug Administration (FDA) requires the cerliponase alfa manufacturer to further evaluate the safety of cerliponase alfa in CLN2 patients below the age of two years, including device related adverse events and complications with routine use. In addition, a long-term safety study will assess cerliponase alfa treated CLN2 patients for a minimum of ten years.The application for cerliponase alfa was granted priority review designation, breakthrough therapy designation, orphan drug designation, and a rare pediatric disease priority review voucher. The FDA granted approval of Brineura to BioMarin Pharmaceutical Inc. Structure and biomolecular mechanism
Cerliponase alfa is an approximately 59 kDa molecule that codes for 544 amino acids in its proenzyme form while the activated mature enzyme only codes for 368 amino acids. Five amino acid residues have N-linked glycosylation sites. These five residues have additional mannose-6-phosphate (M6P) targeting sequences which function to target enzymes to the lysosome. When the cerliponase alfa proenzyme reaches target neurons during administration, it binds mannose-6-phosphate receptors on the cell surface to trigger vesicle formation around the receptor-proenzyme complex. The more neutral pH of the cytosol promotes binding of the proenzymes M6P targeting sequences to their receptors.
One effect of aging and disc degeneration is that the nucleus pulposus begins to dehydrate and the concentration of proteoglycans in the matrix decreases, thus limiting the ability of the disc to absorb shock. This general shrinking of disc size is partially responsible for the common decrease in height as humans age. The anulus fibrosus also becomes weaker with age and has an increased risk of tearing. In addition, the cartilage endplates begin thinning, fissures begin to form, and there is sclerosis of the subchondral bone. Since the fissures are formed in the anulus fibrosus due to osteo-arthritic bones or degeneration in general, the inner nucleus pulposus can seep out and put pressure on any number of vertebral nerves. A herniated disc can cause mild to severe pain such as sciatica and treatment for herniated discs range from physical therapy to surgery. (see also: Intervertebral disc arthroplasty) Other degeneration of the vertebral column includes diffuse idiopathic skeletal hyperostosis (DISH) which is the calcification or ossification of the ligaments surrounding the vertebrae. This degeneration causes stiffness and sometimes even curvature in the lumbar and thoraco-lumbar spinal region. Burgeoning evidence suggests that long-term running may mitigate age-related degeneration within lumbar intervertebral discs

Scoliosis
While this may not cause pain in some people, in others it may cause chronic pain. Other spinal disorders can affect the morphology of intervertebral discs. For example, patients with scoliosis commonly have calcium deposits (ectopic calcification) in the cartilage endplate and sometimes in the disc itself.