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

听

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 (秀色直播)

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)

听

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 秀色直播 Health Centre)

Co-investigators: Thomas Durcan (秀色直播), Timothy Kennedy (秀色直播), 秀色直播), Philippe Huot (秀色直播)

Collaborators: Guillaume Bourque (秀色直播), Masad Damha (秀色直播), Pieter Cullis (University of British Columbia), Ian Willis, (Albert Einstein College of Medicine), Austen Milnerwood (秀色直播), Nahum Sonenberg (秀色直播), 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 (秀色直播), 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)

听

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 (秀色直播), Morag Park (秀色直播)

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

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

Post-doctoral fellows: Rocio Conforti Ayelem (秀色直播), Zohreh Mehrjoo (秀色直播), Monica Lara Marquez (秀色直播), Behrang Sharif (秀色直播)

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)

听