TLI Investigator Dr. Lynda Polgreen’s Study Published in Nature Medicine Showing Promising New Treatment for Sanfilippo Syndrome

The study found that anakinra is safe and effective in improving neurobehavioral and functional outcomes for patients with Sanfilippo syndrome

Dr. Polgreen

The groundbreaking study was led by Lynda Polgreen, MD, MS,  Investigator at The Lundquist Institute for Biomedical Innovation (TLI) and Associate Professor of Pediatrics at the David Geffen School of Medicine at UCLA, focused on using anakinra, a recombinant interleukin-1 receptor antagonist, on addressing the neuroinflammation component of Sanfilippo Syndrome. Neuroinflammation is believed to be a significant contributor to the progression of neurological damage in the syndrome. Anakinra works by inhibiting interleukin-1 (IL-1), a key cytokine that mediates the inflammatory response. By blocking the activity of IL-1, anakinra can reduce inflammation and possibly slow or prevent the progression of neurological damage.

Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is considered an orphan disease, affecting fewer than 200,000 people at any given time, which classifies it for special considerations in drug development and policy. It is a rare genetic disorder characterized by the body's inability to break down certain complex molecules. This results in the accumulation of these molecules in cells, leading to severe neurological symptoms, including developmental delay, behavioral problems, and progressive dementia. It is a lysosomal storage disease caused by gene mutations that code for specific enzymes that break down glycosaminoglycans (GAGs).

In the phase 1/2 trial, researchers evaluated anakinra's safety, tolerability, and effects on neurobehavioral, functional, and quality-of-life outcomes in patients with Sanfilippo syndrome. The study involved 23 participants, 75% of whom required a dose increase due to the disease's progression or insufficient initial response at either week eight or sixteen. Despite these adjustments, the trial results were promising, with significant improvements noted in multiple domains of the multi-domain responder index (MDRI), a tool used to assess a range of symptoms and functions.

By week 36, 94% of the remaining participants showed improvement in at least one domain, indicating substantial gains in their ability to perform daily functions and an enhanced quality of life. The majority of adverse events were mild, with injection site reactions being the most common. Crucially, no serious adverse events related to the use of anakinra were reported, underscoring its safety profile.

Dr. Lynda Polgreen, the study's principal investigator, expressed optimism about the results, "The improvements we observed in our patients are not merely clinical statistics; they represent significant strides in the day-to-day lives of individuals battling with Sanfilippo syndrome. This trial highlights the potential of anakinra as a treatment option and underscores the broader importance of advancing research and development for rare diseases. Every new therapy we develop provides invaluable insights and hope, not just for patients and their families, but for the entire medical community as we strive to understand and tackle these complex conditions."

This study supports the potential of anakinra as a therapeutic option for Sanfilippo syndrome. It opens the door to its application in other mucopolysaccharidoses and similar neurodegenerative disorders characterized by neuroinflammation. With these encouraging results, further research is vital to explore the full potential of anakinra in changing the trajectory of Sanfilippo syndrome and providing hope to affected families worldwide.

The article DOI: 10.1038/s41591-024-03079-3

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