Cure Sanfilippo Foundation is funding a two-year project by Neta Shlezinger, PhD, at the Koret School of Veterinary Medicine in Israel, in collaboration with Dr. Annick Raas-Rothschild, Associate Professor and Director of Rare Diseases Institute at Sheba Institute for Rare Diseases at The Emond and Lily Safra Children’s Hospital. This project seeks:
- To determine the role of glycosaminoglycan (GAG) degradation in antifungal immunity; and
- To define the Sanfilippo syndrome (MPS III) airway microbiome and establish its role in pathogenesis of MPS-associated pneumonia.
Respiratory infections affect approximately 90% of patients with MPS. Pneumonia is one of the leading causes of mortality in Sanfilippo syndrome Types A and B. Remarkably, the etiology for the majority of MPS-associated pneumonia remains unknown.
Dr. Shlezinger has discovered that the innate immune-response to phagocytosed fungal cells includes up-regulation of the glycosaminoglycan (GAGs) degradation pathway in activated neutrophils. This process is triggered by fungal GAGs, fungal cell wall components essential for biofilm formation and immune response modulation during invasive infection.
Her findings indicate that host degradation of fungal GAGs is a general feature of the anti-fungal immunity. Moreover, studies suggest that GAGs build-up may facilitate microbial invasion and niche establishment, yet, little is known about the underlying mechanisms and the impact on the pathogenesis of MPS-associated pneumonia.
This project will leverage the power of bedside-to-bench research, teaming-up with Prof. Raas-Rothschild of the Sheba Institute for Rare Disease, a leading physician-scientist in the field of pediatric rare diseases. Animal models of MPS IIIA and B and a cohort of children with MPS IIIA will be studied to better understand the role of GAGs in recurrent respiratory infections.
“This research may help us understand why pneumonia is the leading cause of death in Sanfilippo syndrome and may lead to better therapeutic strategies to treat lung infections,” said Dr. Cara O’Neill, Chief Science Officer for Cure Sanfilippo Foundation. “This will also provide information on the microbiome and mycobiome of Sanfilippo patients that is an important understanding from which future research can build.”
“I am absolutely thrilled about this program, and I think that a key to successful translational and impactful research is collaborative work of scientists and physicians, beginning at the bedside, to turn scientific discoveries into healthcare solutions for patients. Bedside-to-Bench-to-Bedside,” said Dr. Shlezinger.