Clemson University researchers are investigating four existing FDA-approved drugs as potential treatments for Sanfilippo syndrome, a rare neurodegenerative disorder that affects children and is often referred to as childhood Alzheimer's disease. The study, funded by the Cure Sanfilippo Foundation, represents a novel drug repurposing approach that could significantly accelerate treatment development for this fatal condition.
Disease Mechanism and Current Challenges
Sanfilippo syndrome is characterized by the accumulation of heparan sulfate in cellular lysosomes due to enzyme deficiencies. This buildup causes progressive brain damage, leading to loss of speech, mobility, eating ability, and sleep function. Children typically appear healthy at birth but gradually deteriorate, with most patients dying during their teenage years.
"We know the cause, but what we don't understand is why," said Trudy Mackay, director of the Clemson Center for Human Genetics. The syndrome affects cellular function at the lysosomal level, where the absence of critical enzymes prevents proper breakdown of heparan sulfate molecules.
Fruit Fly Model Advantages
The research team is utilizing Drosophila melanogaster (fruit flies) as a model organism to test drug efficacy. This approach leverages significant genetic similarities between humans and fruit flies, with Mackay noting that "70% of human disease genes have fruit fly counterparts."
The fruit fly model offers several advantages for Sanfilippo syndrome research, including rapid generation times, well-characterized genetics, and the ability to conduct high-throughput screening of multiple compounds simultaneously.
Drug Repurposing Strategy
Rather than developing new compounds from scratch, the Clemson team is focusing on four drugs already approved for other indications. "They are approved for something else currently, but they are safe for children to take," Mackay explained. This strategy could substantially reduce development timelines and costs.
Robert Anhold, Provost Distinguished Professor of Genetics at Clemson University, emphasized the economic benefits of this approach: "These days there is a realization that instead of starting from scratch, spending millions and millions of dollars and many years to get it to market, let's look at these thousands of drugs we already have."
Clinical Translation Timeline
If the fruit fly studies demonstrate promising results, the research team plans to advance to human clinical trials. The O'Neill family, whose 15-year-old daughter Eliza has Sanfilippo syndrome, hopes these trials could begin at the Greenwood Genetic Center within the next few years.
The urgency of this timeline reflects the progressive nature of the disease. "As we know Sanfilippo is fatal," said Cara O'Neill, Eliza's mother. "It's a neurodegenerative disease and time is of the essence."
Foundation Support and Family Impact
The Cure Sanfilippo Foundation, established by Glenn and Cara O'Neill following their daughter's diagnosis, has grown from a single family initiative to a network of 150 partner families worldwide over 11 years. This foundation provides crucial funding for research initiatives, including the current Clemson study.
The O'Neill family's experience illustrates the devastating impact of Sanfilippo syndrome on families. "It was difficult when we got the diagnosis, you are told your child is basically going to fade away and die in the next decade," Glenn O'Neill said. "It throws everything upside down, your entire life."
Research Implications
The Clemson study represents a pragmatic approach to rare disease drug development, combining established model organisms with existing pharmaceutical compounds. This methodology could serve as a template for other rare disease research programs, particularly those affecting pediatric populations where traditional drug development timelines are inadequate.
The research addresses a critical unmet medical need, as no approved treatments currently exist for Sanfilippo syndrome. Success in this drug repurposing effort could provide hope for affected families while demonstrating the value of innovative research approaches in rare disease therapeutics.
