Cure Sanfilippo Foundation is sponsoring an “Open-label Study of Anakinra in MPS III” clinical trial in collaboration with The Lundquist Institute (formerly LABiomed), and Sobi (Swedish Oprhan Biovitrium AB).
This study is an open-label, single-arm, no placebo or control group trial of the IL-1 antagonist drug Kineret. The goal of the study is to determine if a number of disease symptoms can be improved by treatment with Kineret, thereby improving patients’ quality of life.Read the trial’s full listing on ClinicalTrials.gov.
This drug is already FDA approved for several indications, one of which is a pediatric disorder. Testing an existing drug for a new disease, as in this trial, is called “drug repositioning” or “drug repurposing.”
Pre-clinical research has shown that reducing inflammation can impact symptoms of the disease. However, unlike steriods which are often used to combat inflammation, Kineret does not carry the same side effects of long-term steriod use.
Study DescriptionInflammation has been connected with disease pathogenesis in the MPS disorders. Therapies aimed at decreasing inflammation are currently being studied in many MPS disorders and showing benefits.
IL-1 is a cytokine molecule involved in the inflammatory cascade. Research into the animal model of MPS III has identified IL-1 as a major target for addressing inflammation in the body and brain of affected animals. Blocking the ability to respond to IL-1 has shown benefits in the progression of brain disease and behavior in MPS III animals. (Read more about this research at https://www.embopress.org/doi/full/10.15252/emmm.201911185.) Thus, the use the IL-1 receptor blocker, anakinra (Kineret), holds significant potential to improve behavioral and other problems in children with MPS III.
This study will be assessing for beneficial changes in a number of disease related symptoms. Some of these include, but are not limited to, improved behavior, sleep, stooling, communication, mood, and mobility; as well as decreased seizure frequency, disordered movement, and fatigue as they may apply to each individual.
Administration of Kineret does not impact the primary disease enzyme deficiency of Sanfilippo syndrome. However, due to the cascade of detrimental effects from the primary disease, evidence would suggest that addressing this target in the inflammatory cascade could help slow or improve some of the secondary disease effects.
This study is open for any Type of Sanfilippo (A, B, C, D).
Study Contact InformationIn December 2019, the trial was listed as “Enrolling” on ClinicalTrials.gov.
Study contact: Adolfo Morales, The Lundquist Institute, 310-357-9023, email@example.com.
Cure Sanfilippo Foundation is funding search to explore re-positioning FDA-approved compounds using cell-based, high-content screening in Sanfilippo Syndrome (MPS III) cell models.
Awardee: Diego Medina, PhD- Telethon Institute of Genetics and Medicine (TIGEM)- Italy
Start Date: June 2018
UPDATE: October 2019
In October 2019, TIGEM presented preliminary results of this study at the Conference of Telethon Fundamental Associations in Italy. Read more.
Target Amyloid Aggregation as a New Therapeutic Approach to Treat the Central Nervous System in Sanfilippo SyndromeCure Sanfilippo Foundation has awarded funds to the Telethon Institute of Genetics and Medicine (TIGEM) in Italy to study the effect of a new drug compound on the buildup of toxic proteins in the brains of those affected by Sanfilippo Syndrome.
Project lead Alessandro Fraldi specializes in the study of neurodegeneration in lysosomal storage diseases (LSDs) and novel treatment approaches. Under his lead, the Fraldi team aims to build upon their preliminary data supporting the effects of a novel drug compound in reducing the effects of harmful accumulated proteins in the brain of Sanfilippo animals. The drug functions by a different mechanism of action than previously tried in other neurodegenerative diseases characterized by protein aggregation.
“We are pleased to support this new approach to addressing a key feature of neurodegeneration. The many biochemical similarities among neurodegenerative conditions like Alzheimer’s Disease, Parkinson’s Disease and Sanfilippo Syndrome are striking. Research aimed at these common features offers the opportunity to find ways to improve the lives of loved ones with these devastating conditions”, said Dr. Cara O’Neill, Scientific Director of Cure Sanfilippo Foundation.
Initial proof of concept work has been conducted using the MPSIIIA mouse model. Inclusions of aggregated proteins was shown to be a general feature of MPSIIIA brain disease in which such aggregation progressively builds up as neurodegeneration is seen. Preliminary data indicates that the drug is able to clear protein aggregation, thus reducing inflammation and oxidative stress.
In this project, a large efficacy study will be performed testing the drug’s effects on toxic protein clearance, inflammation, nerve signaling, and behavior in MPSIIIA mice. Dr. Fraldi has also assembled a team of collaborators to further evaluate these findings in the other subtypes of Sanfilippo syndrome (MPSIIIB-D).
Start Date: April 2018
Cure Sanfilippo Foundation and Sanfilippo Children’s Foundation (Australia) are delighted to announce we have collaborated again. This joint grant funding is to the Australian Regenerative Institute at Monash University in Melbourne to create a zebrafish model of Sanfilippo. The project, led by zebrafish disease modelling expert Dr. Jan Kaslin and team, aims to produce a new tool to be used in the fight against Sanfilippo!
Dr. Cara O’Neill, Scientific Director of Cure Sanfilippo Foundation said: “We’re pleased to support Dr. Kaslin’s work which will create a new experimental model for the study of Sanfilippo. Unique aspects of the zebrafish model offer the potential to accelerate the rate of drug discovery for children who are in dire need.”
“We’re excited to be funding this project that could open up new avenues for Sanfilippo research around the world, providing a new tool for understanding this devastating condition and developing much-needed new therapies,” said Megan Donnell, Executive Director of the Sanfilippo Children’s Foundation.
Zebrafish are a useful research tool because they allow quick and precise understanding of the mechanisms of disease and can be used in the search for drugs. Zebrafish have already been used to help unlock a number of biological processes behind diseases such as muscular dystrophy. Zebrafish are transparent so the cellular processes inside their bodies can be watched in real-time under a microscope.
Start Date: February 2018
Engineering Mesenchymal Stem Cells (MSCS) to Produce Sulfamidase for Intrathecal Treatment of Sanfilippo Syndrome
Awardee: Jan Nolta, PhD, Director of UC Davis Stem Cell Program, University of California Davis, Institute for Regenerative Cures
Start Date: August 2017