In February 2019 Sanfilippo Children’s Foundation Executive Director Megan Donnell and Research Manager Dr Kristina Elvidge attended the 15th Annual WORLD Symposium, held in Orlando in the USA. The conference is designed for researchers, pharmaceutical companies, patient organisations, clinicians, and all others who are interested in learning more about the latest discoveries related to lysosomal diseases.
Sanfilippo Syndrome is one of about 50 lysosomal storage diseases – inherited metabolic diseases that are characterised by an abnormal build-up of various toxic materials in the body's cells as a result of enzyme deficiencies. It was encouraging to see so many presentations for Sanfilippo (MPSIII) as well as new innovations for other similar conditions which could be translated into benefit for Sanfilippo in the future.
Highlights from the formal presentations relevant to Sanfilippo are detailed below. In addition to the presentations, productive meetings were held with companies, researchers and Sanfilippo foundations from around the world.
Preclinical/Basic research
- Dr. Claire O’Leary and Prof. Brian Bigger presented a poster on determining the optimal administration method for Sanfilippo Type C gene therapy. It involves catheters in the brain to ensure distribution of the gene-carrying virus to all regions of the brain. This knowledge will be used for the design of the Sanfilippo Type C gene therapy clinical trial that is in the planning stages and could also be applied to the other Sanfilippo subtypes.
- Dr. Kimberly Hawkins from Dr. Coy Heldermon’s lab at the University of Florida presented research on the ketogenic diet in mice with Sanfilippo Type B. She showed in her poster that mice on a ketogenic diet (high fat, moderate protein and minimal carbohydrate) had an improved metabolic profile in their brains but there was no reduction in the accumulation of heparan sulfate (GAGs). This was a short-term study and more research is required to see if this diet could be helpful for children with Sanfilippo.
- Dr. Cara O’Neill presented results of a study that used a facial recognition smart phone app (Face2Gene) to develop a diagnostic tool for Sanfilippo Type B. It is hoped that this technology may help doctors diagnose Sanfilippo Syndrome earlier.
- Dr. Maria Fuller presented on new methods to diagnose Sanfilippo and other MPSs in blood and urine samples.
- Several presentations focused on newborn screening for lysosomal disorders. In the era of emerging treatments that need to be administered as early as possible, this is an important issue.
Clinical trial results
BioMarin’s ERT for Sanfilippo Type B
Data from BioMarin’s trial was presented orally and in a poster by Dr. Maureen Cleary from Great Ormond Street Hospital in London. Nine children have now been treated in the trial for more than 24 weeks. The participants had weekly infusions of tralesinidase alfa directly into the brain (ICV) via a port implanted under the scalp. Heparan sulfate in the cerebrospinal fluid was shown to decrease into the normal range and participants livers reduced to normal size. Of seven participants who have had their cognitive function assessed for more than 24 weeks, five showed encouraging signs of stabilisation but further data will be needed to prove the effectiveness of this potential treatment.
Over 500 doses of the enzyme replacement therapy have been administered. There were side effects – mostly due to the invasive delivery method, some are considered serious such as meningitis infection in one participant. The ERT is considered generally safe and well tolerated but it was anecdotally reported by Dr. Cleary that two participants have recently withdrawn from the study due to side effects.
The trial is ongoing and 17 more participants who participated in the BioMarin natural history study are now enrolled for treatment with no data currently available yet.
Abeona’s gene therapy for Sanfilippo Type A
Dr. Kevin Flannigan from Nationwide Children’s Hospital presented results of Abeona’s gene therapy trial for Sanfilippo Type A. Fourteen children are now enrolled in the Sanfilippo Type A study in the US, Spain and Australia and have been treated at one of three different doses.
The gene therapy continues to be safe and tolerable and reductions in heparan sulfate, the toxic substance that builds up in children with Sanfilippo, have been seen in both the urine and the cerebral spinal fluid (CSF). The liver, which is enlarged in children with Sanfilippo, was also reduced at all three doses.
Information available so far on cognitive function after treatment is limited but the trend emerging is that younger, higher functioning children are showing some stabilisation or improvement of their cognitive ability according to the testing used. Caregiver observations have reported additional benefits such as improved sleep and attention. Abeona will focus their recruitment on younger patients for the remainder of this trial with the minimum age now lowered to six months.
SOBI’s ERT for Sanfilippo Type A
SOBI, a biopharmaceutical company based in Stockholm, presented a poster on the design of their phase 1/2 trial of their enzyme replacement therapy called “SOBI003” for Sanfilippo Type A. All three participants in the low dose group have started receiving weekly IV infusions. SOB1003 is a version of the enzyme that is missing in Sanfilippo Type A which has been chemically modified so that it lasts for longer inside the body and crosses the blood brain barrier.
The study aims to assess the safety, tolerability and efficacy of SOBI003 in nine children in the USA and Turkey aged 1-6 years with Sanfilippo Type A. The enzyme will be given by weekly intravenous (IV) infusion.
