Landmark Nature Medicine Study Reports Promising New Treatment Reduces Suffering in Sanfilippo syndrome
June 21 2024 - 8:00AM
As a neurodegenerative disease characterized by childhood onset
dementia, Sanfilippo syndrome causes immense suffering in many
ways, including pain, loss of speech, extreme agitation, and
distress, gastrointestinal symptoms, and profound sleep
disturbance. With no approved treatment, clinical specialists have
had few options to help alleviate this suffering until now. A
groundbreaking clinical trial collaboration between study lead and
principal investigator Lynda Polgreen, MD, MS, Investigator at The
Lundquist Institute for Biomedical Innovation at Harbor-UCLA (TLI)
and Associate Professor of Pediatrics at the David Geffen School of
Medicine at UCLA and Cure Sanfilippo Foundation’s Chief Science
Officer and study co-investigator, Cara O’Neill, MD, FAAP, used an
innovative approach to treat this disease by targeting
neuroinflammation, as it is thought to be a key contributor to
disease symptoms.
Dr. Polgreen’s team used anakinra, a recombinant interleukin-1
receptor antagonist, in children and young adults with moderate to
advanced stages of the condition, meaning they were all
experiencing debilitating, life-limiting symptoms at the time of
study enrollment. While ongoing clinical trials are searching for a
cure for Sanfilippo syndrome, such trials are restricted to
specific disease subtypes and include only the youngest of children
exhibiting very few symptoms because the disease is considered
irreversible. This has left more than 99% of the Sanfilippo
population without any opportunity to receive focused treatment.
However, the research team’s revolutionary clinical study was
designed to improve the representation of this long-excluded
segment of the Sanfilippo community by treating individuals who
have already been significantly impacted by their disease.
Sanfilippo syndrome, also known as mucopolysaccharidosis type
III (MPS III), is considered an orphan disease, which classifies it
for special considerations in drug development and policy. It is a
rare genetic disorder in which the body is unable to break down the
complex molecule heparan sulfate. Accumulation of heparan sulfate
in cells then triggers several biological consequences, including
inflammation, ultimately leading to progressive dementia and
body-wide disease. Anakinra works by inhibiting interleukin-1
(IL-1), a key mediator of the inflammatory response. By blocking
the activity of IL-1, anakinra reduces harmful inflammation in the
body and brain. For the first time, this study provides evidence
that anakinra can positively impact meaningful disease symptoms in
patients with Sanfilippo syndrome.
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 several subtypes of
Sanfilippo syndrome. Results showed anakinra was safe and
associated with significant improvements in multiple symptom
domains. By week 36 of treatment, 94% of participants showed
improvement in at least one domain. Most 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 changes we observed in
our patients represent significant improvements in the day-to-day
lives of individuals with Sanfilippo syndrome and their families.
This trial highlights the potential of anakinra as an adjunctive
treatment option and underscores the broader importance of
targeting downstream effects, such as inflammation, in lysosomal
diseases."
“Together with Dr. Polgreen, we recognized an opportunity to
translate existing preclinical proof of concept research into a
drug repurposing trial which had the potential to benefit children
imminently. Cure Sanfilippo Foundation is proud to have partnered
with and supported this highly skilled and compassionate research
team led by Dr. Polgreen (TLI), including the expertise of Dr.
Eisengart (University of Minnesota) and Dr. Chen (TLI), to address
the urgent needs of the patient community. We are also grateful to
have collaborated with Sobi, who generously provided study drug.
This close collaboration and integration of patient/caregiver
perspectives have facilitated using novel outcome instruments and
patient-centered study design that will inform future drug
development in this ultra-rare disease,” reflected Dr. O’Neill.
“Funding provided by Cure Sanfilippo Foundation to support all
clinical trial activities and patient travel was made possible by
generous donors and families who support the Foundation’s mission;
creating new opportunities to transform lives. We look forward to
partnering with The Lundquist Institute to advance additional
clinical programs,” said Cure Sanfilippo Foundation President and
Co-Founder Glenn O’Neill.
“This study has made immediate strides toward addressing the
need to help all people touched by this condition, regardless of
their level of disability,” noted Julie Eisengart, Ph.D., Associate
Professor of Pediatrics and Director of the Neurodevelopmental
Program in Rare Disease at the University of Minnesota Medical
School. “This trial shows promise for improving the lived
experience of not only the people diagnosed with Sanfilippo
syndrome, but also their families who face countless
disease-related stressors and heartache.”
This study supports the potential of anakinra as a therapeutic
option for Sanfilippo syndrome. It opens the door to its
application in other MPS 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.
Max Benavidez
The Lundquist Institute for Biomedical Innovation
310-200-2682
max.benavidez@lundquist.org