Poster Session 3, 1:15 PM - 2:00 PM: Room 165 [D7]

Development a Stable Cell Line for the Production of a Less Immunogenic GALNS Enzyme for the Treatment of Morquio A Disease

Presenter: Tuana Yuzer

Faculty Sponsor: Adriana M. Montano

School: UMass Amherst

Research Area: Biochemistry and Molecular Biology

ABSTRACT

Mucopolysaccharidosis (MPS) IVA also known as Morquio A disease, results from the deficiency of N-

acetylgalactosamine-6-sulfatase (GALNS) needed to break down the glycosaminoglycans (GAGs) chondroitin-6-sulfate

and keratan sulfate. The accumulation of these GAGs leads to symptoms such as enlarged liver and/or spleen, ocular,

hearing and heart disease, among others. There is no cure for Morquio A, the only FDA approved treatment for Morquio A

is Enzyme Replacement Therapy (ERT). Some of the problems associated with ERT are low penetration of hypovascular

tissue, low half life (2.4 mins for native GALNS), immune reaction to the enzyme, and high cost. Immune reaction to ERT

is driven by Cross Reactive Immunogenic Material status of the patient and environmental changes. Our goal is to minimize

the immunogenicity of the enzyme by detecting the most immunogenic regions of GALNS enzyme through MHC binding

and T cell epitope prediction and altering the sequences to make it less immunogenic. Sequences of those sites that were

altered and showed no significant changes to the structure and function compared to the original GALNS were selected.

Seven GALNS sequences were further analyzed after 324 permutations of the most immunogenic sites. Here, we created

stable cell lines for the production of the less immunogenic enzymes for further in vitro and in vivo applications. Our long-

term goal is to develop a safer and more effective ERT for Morquio A by reducing the immunogenicity of GALNS,

improving treatment outcomes, and quality of life for patients.

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