October 5, 2023
Welcome to our next Researcher Spotlight, where we highlight our research partners and their efforts to advance treatments for rare and ultra-rare diseases.
Meet Zhenya Ivakine, PhD from the Ivakine Lab at the The Hospital for Sick Children (SickKids) in Toronto, Canada! In this conversation, we dive into the groundbreaking research being conducted at the Ivakine Lab and their partnership with Cure Rare Disease.
What does the Ivakine Lab research?
The Ivakine Lab is focused on developing genome editing-based strategies to treat many diseases including Duchenne muscular dystrophy (DMD), cystic fibrosis, and MECP2 duplication syndrome.
The lab is also researching methods to classify variants of unknown significance (VUS), which are genetic variants whose pathogenicity is currently unknown. In other words, it is still uncertain whether these genetic changes may be responsible for causing a disease or are benign. Genetic variants are commonly identified as ‘pathogenic’, ‘likely pathogenic’, ‘uncertain significance’, ‘likely benign’, and ‘benign’ (as recommended by the American College of Medical Genetics and Genomics). By developing techniques to improve the classification of VUS, researchers and physicians will be better equipped to diagnose patients with genetic disorders and develop therapeutics to target those mutations.
What projects are the Ivakine Lab working on in collaboration with Cure Rare Disease?
In partnership with CRD, the Ivakine Lab, in close collaboration with the Cohn Lab, is advancing genome-editing strategies to correct genetic mutations causing DMD. The labs were the first to correct a duplication mutation in exons 18-30 of the dystrophin gene and are currently working on a variety of DMD-causing duplication mutations with Cure Rare Disease. They are employing a single guide strategy, in which they can remove a duplication, thereby restoring production of the full-length dystrophin protein.
Additionally, the Ivakine Lab is working on smaller mutations, which involve codons (sequences of 3 nucleotides that either encode a specific amino acid or signal the end of protein synthesis) being out of the reading frame, preventing the production of full-length, functional dystrophin. Reframing strategies can be employed in an effort to restore the reading frame in which a small number of nucleotide base pairs can be inserted into or deleted from the gene. The Ivakine Lab is also researching exon skipping strategies to correct the open reading frame that would result in production of a truncated but functional dystrophin protein.
Why did you choose to work with CRD?
The Ivakine Lab has pioneered several genome editing strategies in correcting patient mutations in vitro and in vivo, revealing the possibility to prevent development of a disease, as well as slow down or even reverse disease progression.
The next step is definitely to try to bring this technology close to patients, and I think this collaboration with Cure Rare Disease allows for that. This is the closest translational path that I am seeing. Everything that we are doing is towards bringing therapies to these kids.
Are there any exciting milestones or upcoming projects you have in partnership with CRD that you are looking forward to?
The lab has recently accomplished a challenging task: the generation of a single copy humanized DMD (hDMD) mouse model. The most common hDMD model currently in use is a duplication model for the humanized dystrophin gene, making it difficult to model patient mutations. This new model will allow for more efficient modeling of disease-causing mutations and subsequent testing of therapeutic constructs in vivo.
Thank you to Dr. Ivakine for sharing these important updates about the research being done in his lab. Through the lab’s dedicated efforts, they are making significant advances towards developing therapies for those affected by rare genetic diseases and we are grateful to have them as partners in our mission.