Sanfilippo syndrome is a rare genetic disorder in which the body is unable to break down the complex molecule heparan sulfate. The condition is characterized by childhood dementia with severe symptoms including pain, loss of speech, extreme agitation and distress, gastrointestinal symptoms and profound sleep disturbances. In the absence of an approved treatment, specialists have few options to alleviate this suffering.
The study, a groundbreaking clinical trial, uses an innovative approach to target neuroinflammation, considered a key contributor to disease symptoms. Specifically, the team is testing anakinra, a recombinant interleukin-1 receptor antagonist, in child and young adult participants with moderate to advanced stages of the syndrome. All participants presented with debilitating and life-limiting symptoms at baseline.
Until now research has been limited to specific subtypes of the disease including only younger children with very few symptoms. This left more than 99% of affected patients “left behind”. The new study, however, was designed to improve the representativeness of this group of patients.
Target neuroinflammation
Sanfilippo syndrome is characterized by the accumulation of heparan sulfate in cells triggers several biological consequences, including inflammation, which ultimately leads to progressive dementia and systemic damage.
The drug Anakinra works by inhibiting interleukin-1 (IL-1), a key mediator of the inflammatory response. By blocking IL-1 activity, anakinra reduces harmful inflammation in the body and brain.
The study provides evidence of the positive impact of anakinra on the symptoms of Sanfilippo syndrome. Specifically, this phase 1/2 trial, which evaluated the safety, tolerability and effects of anakinra on neurobehavioral, functional outcomes and quality of life of participants, reveals that:
- anakinra was safe and associated with significant improvements in several types of symptoms;
- at the 36th week of treatment, 94% of participants showed improvement in at least one type of symptoms;
- the adverse events recorded are mild, with injection site reactions being the most common effects; no serious adverse reactions related to the use of anakinra have been reported.
Lead author Dr. Lynda Polgreen is very optimistic: “The changes observed in our patients represent significant improvements in their daily lives. This trial highlights the potential of anakinra as an adjunctive treatment option and highlights the broader importance of targeting downstream effects, such as inflammation, in lysosomal diseases.”
