Current projects

Development of core outcome measures

Morquio B and GM1 gangliosidosis study

Learn more about the development of a core outcome set for GLB1-related Morquio B and juvenile or late onset GM1 gangliosidosis (MBD-GM1) study.

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A core outcome set for creatine transporter deficiency (CTD) and guanidinoacetate methyltransferase (GAMT) deficiency

This project aims to address the lack of core outcome measures (COS) and patient meaningful outcome measures (PMO) for Creatine Deficiency Syndromes (CDS), which include AGAT, GAMT, and creatine transporter (SLC6A8) deficiency. These conditions result in intellectual developmental disability (IDD), autism, epilepsy, and cerebral palsy. While some forms of CDS can be partially treated with medical nutrition therapy, there is currently no causal treatment for SLC6A8 deficiency. New therapies are currently being developed for these conditionsm, including pharmacological and gene-based therapies. However, there is no consensus which outcomes should be used in future clinical trials aiming to evaluate the safety and efficacy of these treatments and how to make results of single trials comparable through meta-analysis.

This project intends to develop COS and PMO for CDS through a collaborative approach involving medical experts and patient partners employing established methods, such as systematic literature review, to identify candidate outcomes prioritization through Delphi rounds involving health-care providers experienced in CDS, as well as focus groups with patient caregivers to integrate PMOs. The final deliverable will be a validated set of outcomes, along with standardized measurement tools, enabling future clinical trials to have comparable results and facilitating post-marketing surveillance of new therapies for CDS.

The project is funded by the Association for Creatine Deficiencies (ACD) through the Eugene Washington Engagement Award sponsored by the Patient-Centered Outcomes Research Institute (PCORI)

The principal investigator of the project is Heidi Wallis, ACD (Association for Creatine Deficiencies). Dr. Sylvia Stockler, a pediatrician and biochemical geneticist with experience in treating CDS, is co-principal applicant in the PCORI grant and serves as the scientific advisor. The project protocol was developed through collaborative efforts with Dr. Beth Potter and her team, from the University of Ottawa, and Maureen Smith, a passionate and dedicated patient advocate involved in various national and international patient-partnered research initiatives. This collaboration was part of a larger pan-Canadian project focusing on developing core outcome sets for rare metabolic diseases.

Heidi Wallis and Dr. Stockler play key roles in driving the research forward and ensuring its successful implementation.

Evaluation of potential therapeutic strategies 

CLDN11-related hypomyelinating leukodystrophy (HLD22)

Our goal is to better understand the molecular, cellular, and neuropathological changes caused by mutant claudin-11 and to evaluate potential therapeutic strategies for this disorder. Learn more about the CLDN11-related hypomyelinating leukodystrophy (HLD22) study. 

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Drug repurposing

Repurposeable drug screening for SLC6A8 (cerebral creatine transporter) deficiency

Cerebral creatine transporter deficiency is a genetic cause of intellectual disability. Affecting the uptake of creatine to the brain, patients have almost undetectable levels of this important substance in their nervous system. Current treatment with creatine supplements has limited therapeutic effects. Therefore, the development of new treatments is urgently needed. 

The goal of our research is to find repurposeable drugs for potential rescue of defective creatine transporter function associated with genetic variants in SLC6A8. The ultimate goal is to develop a personalized therapy for people with creatine transporter deficiency.

We are using a pipeline of methods to find drug candidates: during the screening process we use 3D computer modelling and in-silico drug screening/computer-aided drug design), and we test these drugs in experimental HEK cells transfected with SLC6A8 gene variant using single cell patch clamp technique. Drugs that prove effective in recovering electrical currents created by creatine transport through the creatine transporter, are further validated investigating their ability to rescue creatine uptake into cells from affected patients. We use patient fibroblasts as cells, and we use mass spectrometry to measure the uptake. Our pipeline of methods for screening SLC6A8 function in response to existing and new therapeutic molecules will help to customize therapies according to individuals’ genotype and improve outcomes (precision medicine). 

The principal investigator for this project is Dr. Sylvia Stockler, and the co-investigator is Dr. Peter Axerio-Cilies. Collaborators are Aamina Shah (lab tech) and Roger Dyer (Mass spectrometry). 

The project has various funding sources, mainly coming from ACD, the Rare Diseases Foundation and BCCHR.

Repurposeable drug screening for SLC6A1 (GABA transporter) deficiency

Genetic variants in SLC6A1 cause a spectrum of neurodevelopmental disorders characterized by epilepsy, global developmental delay and intellectual disability, autism, and psychiatric disorders such as schizophrenia. Myoclonic‐atonic epilepsy is the most frequently observed seizure type. Standard treatment for controlling the epilepsy is valproic acid by itself or in combination with other anti-epileptic drugs or the ketogenic diet. This treatment helps with seizure activity but does not help the underlying issue, and therefore, this treatment does not help with intellectual disability, language impairment, and behavioural issues. Therefore, there is an urgent need to identify new treatments that would treat the underlying neurological issues caused by variants on SLC6A1. 

Our goal is to develop a drug repurposing pipeline to treat the underlying neurological issues caused by variants on SLC6A1.

The principal investigator for this project is Dr. Sylvia Stockler and the co-investigators are Dr. Peter Axerio-Cilies and Dr. Michelle Demos.

The project is funded by a private donation to BCCHF.

Industry sponsored clinical trials 

Intrathecal enzyme replacement therapy for lysosomal storage diseases

HGT-HIT-046: An Open-Label Extension of Study HGT-HIT-046 Evaluating Long-Term Safety and Clinical Outcomes of Intrathecal Idursulfase-IT Administered in Conjunction with Intravenous Elaprase® in Pediatric Patients with Hunter Syndrome and Cognitive Impairment. Principal investigator: Dr. Sylvia Stockler; Co-principal investigators: Dr. Ramona Salvarinova, Dr. Manraj Heran.

Embolden: A Global, Multicenter, Open-label, Matched Historical Control Study of Intrathecal SHP611 in Subjects with Late Infantile Metachromatic Leukodystrophy. Principal investigator: Dr. Sylvia Stockler; Co-principal investigators: Dr. Ramona Salvarinova, Dr. Gabriela Horvath, Dr. Catherine Brunel.

Other therapies for lysosomal storage diseases

ELIKIDS: Open label, two cohort (with and without imiglucerase), multicenter study to evaluate pharmacokinetics, safety, and efficacy of eliglustat in paediatric patients with Gaucher disease type 1 and type 3. Principal investigator: Dr. Ramona Salvarinova; Co-principal investigator: Dr. Sylvia Stockler.

Industry sponsored Clinical Trials Disease Registries

Currently open for enrolment

Sanofi rare disease registries (MPS1 and Fabry disease)

The purpose of these registries is to track the natural history and outcomes of patients with rare lysosomal storage diseases treated with enzyme replacement and other innovative therapies. These registries are multi-center, international, longitudinal, observational programs with the ultimate goal to help better guide and assess therapeutic intervention, to assist the rare disease medical community with the development of recommendations for monitoring patients, and to provide reports on patient outcomes to optimize patient care. BC Children’s Hospital is one of these sites. Participation is voluntary and no experimental intervention is involved. Data collected through clinical care is entered into a database and analyzed. This long-term program will proceed for a minimum of 15 years. Principal investigator: Dr. Sylvia Stockler

In vivo metabolic studies

More information coming soon.