The clinical trial results from a phase I/II clinical trial of the anti-inflammatory drug anakinra in multiple subtypes of Sanfilippo syndrome have been published. Results indicate that anakinra used in the study was safe and helped improve behavioural and functional outcomes in patients.
Anakinra is a drug that has been approved by the FDA for the treatment of inflammatory diseases such as rheumatoid arthritis. While the drug cannot address the underlying cause of Sanfilippo (an enzyme deficiency), the study team wanted to investigate whether it may help to reduce the inflammation in the brain in Sanfilippo which is thought to contribute to symptoms. This is based on the evidence from animal and human studies to date that neuroinflammation plays a significant role in the disease. You can read our summary of this here.
The trial aimed to assess the safety, tolerability and effectiveness of anakinra in patients with Sanfilippo, and to explore its potential to ease behavioural and other symptoms to improve quality of life for patients and their families.
The study was run at the Lundquist Institute, UCLA, USA, and was open to anyone diagnosed with Sanfilippo syndrome aged four years or older, regardless of their subtype, whether they had a severe or attenuated form of the disease or had previously received an experimental gene or enzyme replacement therapy. The study enrolled 23 participants between 6–26 years of age who had Sanfilippo type A, B, or C.
All patients were treated with anakinra for 36 weeks via a daily injection under the skin. The injections were performed by caregivers, removing the need for daily hospital trips. Five participants withdrew from the study due to the difficulty of the daily injections, and 13 participants completed the treatment course all the way through to the end of the study.
The most common adverse event experienced was a mild reaction at the injection site, but there were no serious adverse events from the use of anakinra in the trial.
The effect of the treatment on behavioural and functional symptoms and quality of life was assessed through a pre-agreed scoring system based on the most challenging symptoms identified by each family. The parents completed validated symptom assessment questionnaires throughout the study to indicate if there was an improvement, worsening, or no change in their child’s movement disorder, fatigue, pain, behaviour, and sleep disturbance. Parental stress was also evaluated.
By the end of the study, 69% of parents reported a reduction in parental stress, 56% reported improvements in behavioural symptoms, and 44% reported improvements related to signs of pain. The team found that reports of symptom improvement generally correlated with biological measurements that showed reduced markers of inflammation in the blood.
It is important to note that the study did not have a placebo group in which some children received a dummy injection, and all parents and clinicians knew the participants were receiving anakinra. This is noted by the study team as having the potential to affect some of the parental reporting measures used. However, the correlation of symptoms with the biological inflammation markers, and the fact that symptoms returned to pre-treatment levels after the injections stopped, led the study team to conclude that the improvements were indeed due to anakinra treatment rather than a placebo effect and the study supports further investigation into the use of anakinra for the treatment of Sanfilippo.
The trial results have been published in the prestigious scientific journal Nature Medicine. Dr Lynda Polgreen from The Lundquist Institute led the trial, which was funded by and run in close collaboration with Cure Sanfilippo Foundation and their Chief Scientific Officer and Co-Founder, Dr Cara O’Neill.
