The Translational Impact Research (TIR) funding program supports large-scale translational research projects in RNA-based therapeutics, which address D2R鈥檚 strategic priorities, and have a measurable translational impact on the health of Canadians.

In the first funding cycle launched in 2024, 11 Letters of Intent were received of which four were invited to submit full applications. Three full applications were received and awarded. View a summary of the review and selection process.

Funded project听summaries

RNA therapy for a severe and ultra-rare disease

Schinzel-Giedion Syndrome is a devastating and rare genetic disease leading to neurological deterioration and Cystic Fibrosis-like lung disease. Most people with SGS die in the first decade of life and there is no treatment that targets the underlying cause of disease. SGS is caused by missense mutations in the SETBP1 gene which result in an accumulation of the SETBP1 protein. By reducing the level of SETBP1 mRNA, SETBP1 protein levels can be decreased offering a potential treatment for SGS. Using antisense oligonucleotides (ASO), we have successfully reduced SETBP1 protein levels in SGS patient derived progenitor brain cells and SGS mouse disease models. The purpose of this grant is to manufacture and test an RNA therapy for SGS and use it to reduce seizure burden in one SGS individual. We will use a unique clinical trial mechanism in Canada, the Single Patient Clinical Trial. We hope to reduce suffering in the daily life of children suffering from SGS.

Principal investigator: Carl Ernst (海角社区)

Co-investigators : Larry Lands (MUHC), Darcy Wagner (MUHC), Keith Murai (MGH), Ken Myers (MCH), Ziv Gan-Or (MNI), Sebastian Jacquemont (St Justine), Raluca Pana (MNI), Alexander Weil (St Justine), Karl Muchantef (MCH)

Award duration: 3 years

Relevant D2R axes: RNA Therapeutics (Axis 2) Clinical Research, Acceleration, and Implementation (Axis 4) , Population Studies and Genomic Medicine (Axis 1)

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Innovative RNA therapies offer new hope for patients affected by POLR3-related leukodystrophy

Leukodystrophies are rare genetic brain disorders affecting previously healthy children. POLR3-related hypomyelinating leukodystrophy (POLR3-HLD) is characterized by reduced white matter (myelin) production in the brain. It results from mutations in genes that code for RNA polymerase III (Pol III), an essential complex for producing RNA, including transfer RNAs (tRNAs) necessary for protein production. This project aims to develop RNA-based treatments for POLR3-HLD through three strategies: first, using antisense oligonucleotides (ASOs) to target and modify the disease-causing genetic message in affected patients; second, restoring POLR3A function (a critical Pol III subunit) by delivering healthy mRNA via lipid nanoparticles (LNPs); and finally, we are exploring an ASO approach to reduce MAF1, a Pol III inhibitor, to enhance its activity. These therapies will be preclinically tested in cell and mouse models to ensure safety and efficacy, with patient, organization, and industry support to ensure rapid transition to clinical trial.

Principal investigator: Genevi猫ve Bernard (Research Institute of the 海角社区 Health Centre)

Co-investigators: Thomas Durcan (海角社区), Timothy Kennedy (海角社区), 海角社区), Philippe Huot (海角社区)

Collaborators: Guillaume Bourque (海角社区), Masad Damha (海角社区), Pieter Cullis (University of British Columbia), Ian Willis, (Albert Einstein College of Medicine), Austen Milnerwood (海角社区), Nahum Sonenberg (海角社区), Fran莽ois-Xavier Lacasse (Universit茅 de Montr茅al)

Partnering organizations : Jude Tallman and Family, Fondation Les Amis d'Elliot, Leuco Action, Yaya Foundation for 4H Leukodystrophy, Montreal Children's Hospital Foundation, RI-MUHC, Early Drug Discovery Unit (海角社区), NanoCore, C3G Platform, Andor Technology, Dendrotek Biosciences, Parse Biosciences, RNA technologies & Therapeutics Inc.

Award duration: 3 years

Relevant D2R axes: RNA Therapeutics (Axis 2) Clinical Research, Acceleration, and Implementation (Axis 4) , Data Science, Bioinformatics, and Computing in Personalized Medicine (Axis 5)

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The Jerry Pelletier initiative: Diagnostic and therapeutic innovations for rare cancers

Despite great advances overall in cancer therapy, patients with rare subtypes of tumours do not benefit adequately from personalised treatments due to the lack of basic knowledge of the underlying biological factors that drive these cancers. Since these patients often do not respond to standard-of-care approaches and then become resistant to therapies currently available, physicians at present have limited treatment options. We are undertaking a coordinated multi-disciplinary program that will use advanced genomics to identify the most viable biomarkers and likely therapeutic targets for patients with rare types of tumours and then exploit this knowledge to obtain RNA-based and other treatments adapted to each patient. Furthermore, our comprehensive genomic studies and tumour modeling of rare cancer subtypes will generate resources that can be used by the research community to identify new ways to tackle these difficult-to-treat malignancies.

Principal investigator: Mark Lathrop (海角社区), Morag Park (海角社区)

Co-investigators: Gerald Batist (海角社区), Guillaume Bourque (海角社区), Thomas Duchaine, (海角社区), William Foulkes (海角社区), Livia Garzia (海角社区), Sidong Huang (海角社区), Nada Jabado (海角社区), Mark Lathrop (海角社区), Morag Park (海角社区), Ioannis Ragoussis (海角社区), Yasser Riazalhosseini (海角社区), Ramy Saleh (海角社区)

Collaborators: Mark Basik (海角社区), Mathieu Blanchette (海角社区), Julia Burnier (海角社区), Guojun Chen (海角社区), David Juncker (海角社区), Wassim Kassouf (海角社区), Claudia Kleinman (海角社区), Sampath Loganathan (海角社区), Raquel Cuella Martin (海角社区), Heather Melichar (海角社区), William Muller (海角社区), Peter Siegel (海角社区), Hanadi Sleiman (海角社区), Nahum Sonnenberg (海角社区), Simon Tanguay (海角社区), Ian Watson (海角社区)

Post-doctoral fellows: Rocio Conforti Ayelem (海角社区), Zohreh Mehrjoo (海角社区), Monica Lara Marquez (海角社区), Behrang Sharif (海角社区)

Partnering organizations: Oxford Nanopore Technologies, 10x Genomics

Award duration: 3 years

Relevant D2R axes: Population Studies and Genomic Medicine (Axis 1) RNA Therapeutics (Axis 2) , Clinical Research, Acceleration, and Implementation (Axis 4)

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