Unique Clinical Trial Investigates a New Treatment Approach for Sanfilippo Syndrome

June 24, 2020

Trial Continues Despite COVID-19 Pandemic

Investigators at The Lundquist Institute have teamed up with Cure Sanfilippo Foundation for a unique clinical trial that explores whether re-purposing the existing anti-inflammatory drug Anakinra can provide relief to children suffering from Sanfilippo syndrome. Often referred to as “childhood Alzheimer’s,” Sanfilippo is a metabolic disorder that leads to rapid neurological deterioration, suffering, and ultimately death.

While many clinical trials have been interrupted due to the COVID-19 pandemic, the team at The Lundquist Institute pressed forward as safely and quickly as possible so that patients could begin receiving this experimental therapy. With a disease like Sanfilippo, where children are losing ground every day, there is simply no time to waste.

Sanfilippo syndrome, which is also known as mucopolysaccharidosis type III (MPS III), is a rare genetic disease that has devastating effects on the central nervous system; approximately 1 in 70,000 children are born with this inherited, yet initially invisible, condition. Those with the disease lack an enzyme that breaks down large sugar molecules. As those molecules accumulate in their cells—specifically the part of the cell called the lysosome—they cause irreparable damage to the body and brain, including loss of critical brain tissue. The effects of Sanfilippo syndrome typically become apparent at two to three years of age as developmental delays and autism. Tragically, there is no FDA-approved therapy today and the children are essentially left to fade away and die.

The clinical trial was designed by Drs. Lynda Polgreen and Agnes Chen from The Lundquist Institute in collaboration with Cure Sanfilippo Foundation’s Chief Science Officer Dr. Cara O’Neill and Dr. Julie Eisengart, Director of the Neurodevelopmental Program in Rare Disease at the University of Minnesota Medical School.

Dr. O’Neill recognized the potential of emerging research around the role of inflammation in this disease and how existing FDA-approved drugs, such as Anakinra, could ameliorate patients’ symptoms. She sought clinical and pharmaceutical partners to apply this concept in a clinical trial for children with Sanfilippo Syndrome which led her to The Lundquist Institute—and specifically, Dr. Polgreen.

“I am thrilled to join with Cure Sanfilippo Foundation on this very important trial, which is a huge step in working our way toward alleviating suffering from this devastating disease, and understanding the potential role of anti-inflammatory therapies in MPS,” said Polgreen. “Dr. O’Neill has provided a crucial patient-centered voice in discussions with the FDA and investigators regarding this trial’s focus on symptomatic patients, who are largely excluded from other trials.”

The trial, which began in May, involves 20 children with Sanfilippo syndrome, who are given Anakinra, which blocks the activity of interleukin-1 (IL-1), a protein in the body that causes joint damage, thereby reducing inflammation. Re-purposing Anakinra, an existing drug, to treat those with Sanfilippo syndrome could provide a cost-efficient and timely way to improve the quality of life for children who are suffering.

Innovative work done by Prof. Brian Bigger and his team at The University of Manchester inspired this trial by demonstrating that the inflammatory substance IL-1 is a major driver of inflammation in the brain and cognitive decline. Blocking the IL-1 receptor with human IL-1RA in an animal model of Sanfilippo syndrome resulted in correction of memory impairments, hyperactivity, and inflammation throughout the brain and body (Parker et al. EMBO Mol Med. 2020 Feb 14:e11185).

“Our hope is that this study will show that Anakinra, the same IL-1RA product we used to treat Sanfilippo mice, will similarly improve behavioral problems in children with Sanfilippo,” said Prof. Bigger.

“The fastest way to improve the lives of children affected by Sanfilippo and their families is through meaningful, hand-in-hand collaboration among scientists, industry, and parents,” said O’Neill, also a pediatrician and mother to a 10-year-old daughter with Sanfilippo syndrome. “By bringing the scientific and caregiver communities together in the evolution of this trial, we are developing innovative patient-focused, caregiver-informed endpoints that will improve the chance of understanding the true impact and potential benefit of this and any future experimental therapy, streamlining our path to an FDA-approved treatment for Sanfilippo syndrome.”

“This unique partnership allows us the freedom to study some non-traditional outcomes that are very important to this group of patients and their families, but have not been the focus of prior clinical trials in this population,” noted Polgreen.

While Sanfilippo syndrome is considered a rare disease, estimates are that it affects many thousands of children worldwide. This trial is yet another example of The Lundquist Institute’s ethos of taking a holistic view of health.

“At The Lundquist Institute, we pride ourselves on seeking cures and treatments for rare diseases like Sanfilippo syndrome,” said David Meyer, PhD, President and CEO of The Lundquist Institute. “I am proud of Dr. Polgreen’s leadership and the partnership she’s built as they bring new hope to those suffering from this devastating disease.  The Lundquist Institute takes safety extremely seriously, and our first-class facilities allow us to conduct trials like this with extremely sensitive patients.”

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The Lundquist Institute, formerly the Los Angeles Biomedical Research Institute (LA BioMed), is an engine of innovation with a global reach and a 67-year reputation of improving and saving lives. With its new medical research building, its state-of-the-art incubator, “BioLabs at The Lundquist,” existing laboratory and support infrastructure, and a 15-acre tech park in the planning stages, the Lundquist Institute is poised to serve as a hub for the Los Angeles area’s burgeoning biotech scene. The research institute has over 100 principal investigators (PhDs, MDs, and MD/PhDs) working on more than 600 research studies, including therapies for numerous orphan diseases, and is responsible for innovations including the first FDA-approved treatment for sickle cell disease in 20 years. Find out more at https://lundquist.org.AboutCure Sanfilippo Foundation

Cure Sanfilippo Foundation is a 501(c)(3) nonprofit whose mission is to advocate and fund research to bring about treatments and/or a cure for Sanfilippo Syndrome. Cure Sanfilippo has funded 25 research grants around the world which has helped three clinical trials get underway, to date, treating children with Sanfilippo Syndrome. The Foundation creates and explores innovative and breakthrough research to ensure multiple promising paths are being explored in the effort to save children and better their quality of life. In addition to funding research, the Foundation has a focus on: 1) working with the U.S. Food and Drug Administration and biotechs regarding appropriate clinical trial endpoints and ensuring the caregiver voice is being incorporated every step of the way; 2) earlier diagnosis, diagnostic testing, and newborn screening; and 3) providing guidance and support to families for navigating the landscape of clinical trials, insurance and physician support. Learn more about Sanfilippo syndrome and the Foundation at CureSanfilippoFoundation.org.AboutUniversity of Manchester

The University of Manchester is a member of the prestigious Russell Group, is the UK’s largest single-site university with 38,600 students and is consistently ranked among the world’s elite for graduate employability. The University is also one of the country’s major research institutions, rated fifth in the UK in terms of ‘research power’ (REF 2014). World class research is carried out across a diverse range of fields including cancer, advanced materials, addressing global inequalities, energy and industrial biotechnology. No fewer than 25 Nobel laureates have either worked or studied here. It is the only UK university to have social responsibility among its core strategic objectives, with staff and students alike dedicated to making a positive difference in communities around the world. Manchester is ranked 35th in the world in the Academic Ranking of World Universities 2016 and 5th in the UK. The University had an annual income of almost £1 billion in 2015/16. 

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