Canadian GlycoNet Awards $3.9m to 11 Collaborative Research Projects, Including Targets of Sanfilippo Syndrome

Sep 9, 2020 | Canada, CNS, Genetic, News, Rare Diseases, Sanfilippo Syndrome

Canadian GlycoNet Awards $3.9m to 11 Collaborative Research Projects including Targets of Sanfilippo Disease

The Canadian Glycomics Network (GlycoNet) today awarded $3.9 million in grant funding to 11 collaborative research projects. The fund will support a wide range of multidisciplinary research teams across 17 Canadian research institutions and their industry partners to address unmet medical needs in cancer, gastrointestinal inflammations, cystic fibrosis, Sanfilippo syndrome, Parkinson’s, and autoimmune diseases.

Improve Health Burdens in Canada

From prevention to treatment and from tracking to public health policy, these projects aim to mitigate the impact of healthcare burden in Canada and contribute to better understanding of challenging diseases for Canadians. Funded clinical trials, epidemiological observational studies, and other research will accelerate the development of tests, therapeutics, and clinical management of diseases at various levels in our healthcare system.

Sanfilippo Syndrome

A rare genetic disorder, the disease causes fatal brain damage. A type of childhood dementia stopping most patients from ever reaching adulthood. It is considered a rare disease where about 1 in 70,000 children may be born with the inherited condition.

This metabolic disorder means that there are problems with certain chemical reactions occuring in the body. Apparently, its triggered by a deficiency with a particular enzyme that typically breaks down and recycles large complex sugar molecules known as ‘heparan sulphate.’  The disease includes four subtypes (A,B,C,D) and each subtype is associated with a lack of a different enzyme: each one is assigned a different step in the process of breaking down heparan sulphate.

This rare disorder can also be known as lysosomal storage disease or LSD, as the heparan sulphate is stored in a part of the cell known as the lysosome. Additionally, it is known to belong to a group of diseases called Mucopolysaccharidoses (MPS), involving the abnormal accumulation of complex sugars. Another name for the disease is Mucopolysaccharidoses type III or MPS III.

GlycoNet Scientific Director POV

“Investing in health research projects that improve the quality of life of Canadians is part of GlycoNet’s mission,” said Dr. Todd Lowary, Scientific Director, GlycoNet. “These investments also help foster collaborations between academic institutions and industry stakeholders, making the transition of new scientific knowledge, research techniques and collected data into real-world applications faster. Through funding these projects, we want to make sure those who are learning how to treat diseases, who are finding ways to prevent infections, who are inventing new technologies and creating jobs in the industries have the support and facilities they need.”

Who is GlycoNet?

GlycoNet is advancing research, innovation, and training in glycomics–the study of carbohydrates in the biological systems—to improve the quality of life of Canadians. GlycoNet is a one-stop global destination focused on developing new carbohydrate-based drugs, vaccines and diagnostics, in collaboration with academic and industry organizations to address areas of unmet need through applied glycomics research. Funded by the federal Networks of Centres of Excellence (NCE) program and a range of partners, the network includes over 150 researchers across Canada who focus on cancer, chronic diseases, infectious diseases, and neurodegenerative diseases. This national platform supports translational research, protection of intellectual property, novel drug development, company formation and training.

Projects Supported by GlycoNet Include:

Developing next-generation GlycoCaged drugs to treat enteric inflammatory diseases in humans and livestock
This project will explore a new technology that can improve the efficiency of delivering drugs for human patients and livestock afflicted with chronic inflammation in the lower gastrointestinal tract.
Lead Investigator: Harry Brumer (University of British Columbia)
Co-Investigators: Douglas Inglis (Agriculture and Agri-Food Canada), Wade Abbott (Agriculture and Agri-Food Canada), Richard Uwiera (University of Alberta)

Economic evaluation of a novel prostate cancer glycan-based diagnostic tool
This project is the first analysis of the cost-effectiveness of a new sugar-based prostate cancer diagnostic tool. The cost-effectiveness analysis will tell us whether the maximum possible gains from the new test versus status quo or other new technologies are worth their costs, and could contribute to improved patient care and better decision-making of patients, guideline developers and health ministers.
Lead Investigator: Annalijn Conklin (University of British Columbia)
Co-Investigators: Karla Williams (University of British Columbia), Larry Lynd (University of British Columbia), Stanley Liu (Sunnybrook Hospital), Wei Zhang (University of British Columbia)

Systematic characterization of Siglecs and their glycan ligands in cancer
The researchers will study the interactions between carbohydrates on cancer cells and carbohydrate-binding proteins on immune cells to develop therapeutics for patients who do not respond to current cancer immunotherapies.
Lead Investigator: Matthew Macauley (University of Alberta)
Co-Investigators: John Klassen (University of Alberta), Ratmir Derda (University of Alberta), Lisa Willis (University of Alberta), Todd McMullen (University of Alberta)

Anti-exopolysaccharide therapies to improve eradication of early Pseudomonas aeruginosa infection in cystic fibrosis (CF)
The team aims to develop a carbohydrate-based diagnostic tool to identify children CF patients who are likely to fail conventional antibiotic treatment and to give these patients more effective therapies.
Lead Investigator: Valerie Waters (SickKids Hospital)
Co-Investigators: Lynne Howell (SickKids Hospital), Don Sheppard (McGill University), Dao Nguyen (McGill University), Yvonne Yau (University of Toronto)

Lead discovery for inhibitors of lipopolysaccharide (LPS) biosynthesis
Researchers will develop a high-throughput screening platform to discover small molecules that inhibit gram-negative bacteria to develop multidrug resistance.
Lead Investigator: Eric Brown (McMaster University)
Co-Investigators: Chris Whitfield (University of Guelph), Jakob Magolan (McMaster University), Dawn Bowdish (McMaster University)

Mitigation of necrotic enteritis by improving the integrity of intestinal mucin through small molecules and stress management
Researchers will study the effect of milk carbohydrates, derived from dairy residuals, as additives to poultry feed as a non-antibiotic method to maintain bird intestinal health and identify a drug targets to treat flocks that have enteric inflammations. The identified targets will also provide therapeutic insight for diseases in humans such as salmonellosis, Crohn’s disease, colitis, and colon cancer.
Lead Investigator: Wesley Zandberg (University of British Columbia Okanagan)
Co-Investigators: Douglas Inglis (Agriculture and Agri-Food Canada), Wade Abbott (Agriculture and Agri-Food Canada), Alisdair Boraston (University of Victoria), Richard Uwiera (University of Alberta), Steven Smith (Queen’s University), Chantelle Capicciotti (Queen’s University)

Innovate therapies for neurological lysosomal storage disorders
The team will test novel therapeutic approaches including gene/stem cell correction and small molecules to cure or ameliorate Sanfilippo disease, a genetic disease that causes mental retardation, progressive dementia in children leading to early death in their twenties.
Lead Investigator: Alexey Pshezhetsky (CHU Ste-Justine)
Co-Investigators: Christopher Cairo (University of Alberta), Gregory Lodygensky (CHU Ste-Justine), Christian Beausejour (CHU Ste-Justine)

Identification of targets of glucocerebrosidase (GCase) activators and optimization of positron emission tomography imaging agents
Through studying a carbohydrate-processing enzyme, the research team will develop an imaging tool that will shed light on the progression of Parkinson’s disease.
Lead Investigator: David Vocadlo (Simon Fraser University)
Co-Investigators: Vesna Sossi (University of British Columbia), Paul Schaffer (TRIUMF), Edward Fon (McGill University), Thomas Durcan (McGill)

Phase 1/2a clinical trial for treatment of Tay-Sachs and Sandhoff Diseases using AAV9-Hex gene therapy
Researchers will carry out the first Canadian gene therapy trial that removes the excess buildup of glycan-modified fat (GM2 gangliosides) in the brain as a treatment for genetic disorders Tay-Sachs and Sandhoff diseases.
Lead Investigator: Jagdeep Walia (Queen’s University)
Co-Investigators: Inka Brockhausen (Queen’s University), Denis Lehotay (Queen’s University)

Modulatory and therapeutic roles of gangliosides in neurodegeneration and neuroinflammation
The team will study the mechanisms by which gangliosides, a type of glycolipids, protect against neurodegeneration, and determine an optimal method to deliver a potential therapeutic to treat neurodegenerative diseases.
Lead Investigator: Simonetta Sipione (University of Alberta)
Co-Investigators: John Klassen (University of Alberta), Matthew Macauley (University of Alberta)

Regulation of inflammatory response to bacterial infections by human neuraminidase enzymes
Researchers aim to gain a better understanding of the role of neuraminidase enzymes in the immune system during infection. The project will also test inhibitors of these enzymes in treating bacterial infection and autoimmune disease.
Lead Investigator: Christopher Cairo (University of Alberta)
Co-Investigators: Alexey Pshezhetsky (CHU Ste-Justine), Ali Ahmad (Université de Montréal), Don Sheppard (McGill University)

Source: EurekAlert!

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