Unique Clinical Trial Investigates a New Treatment Approach for Fatal ‘Childhood Alzheimer’s’ and Continues Despite COVID-19 Pandemic

Many things were halted because of the pandemic, but a partnership to create an inclusive pathway to treat underserved children was not among them

LOS ANGELES — Investigators at The Lundquist Institute have teamed up with the Cure Sanfilippo Foundation for a unique clinical trial that explores whether repurposing an existing anti-inflammatory drug 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, the 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 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 the 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 will be given anakinra, which blocks the activity of interleukin-1 (IL-1), a protein in the body that causes joint damage, thereby reducing inflammation. Repurposing 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, rather than focusing on diseases that seem to get the most media attention and funding.

“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.”