Drug Rescue and Repurposing: Sibel Naska and Freda Miller

Drug Rescue and Repurposing: Sibel Naska and Freda Miller

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By: Sibel Naska and Freda Miller

Which drug is being investigated for its repurposing potential?

We are investigating a variety of drugs that are approved for use in humans and are being used in the clinic for a wide variety of pathologies.

For what new purpose is the drug being studied?

The drugs are being investigated to increase the activity of neural or dermal stem cells with the final goal to promote tissue repair and regeneration. The idea to undertake this research developed gradually, based on previous work done in our lab or in collaboration with others.

For example, we have shown that the widely-used type II diabetes drug metformin could activate neural precursors in vivo, and thus enhance neurogenesis and hippocampus-dependent memory. Based on these results, we are now testing whether this repurposed drug can be used to recruit endogenous neural stem cells and promote brain repair.

In another study, we discovered an adult dermal stem cell—termed skin-derived precursors (SKPs)—and have shown that SKPs contribute to hair follicle formation, wound healing, and prevent skin from aging. SKPs represent a major therapeutic breakthrough and we are now developing drugs to activate these dermal cells and promote their ability to repair skin under pathological conditions.

What are the research findings?

We use both in vitro and in vivo methods to investigate the aforementioned compounds. Particularly, we have used a high-throughput stem cell-based screening assay to identify compounds already in clinical use that activate stem cells. We then validate the most promising compounds in culture through specific assays.

For in vivo studies, we use different approaches such as drug delivery in genetically modified animals, wound healing models, as well behavioural assays. In collaboration with Dr. Cindi Morshead, we are also using a brain injury model to further assess the efficacy of these drugs.

Excitingly, our data suggest that drugs that increase stem cell activity are also able to promote recovery following brain injury or skin wounds.

What do you hope is the future of the drug in this field?

As we know, the brain does not repair itself after an injury, often times resulting in cognitive deficits and neurodegeneration. On the other hand, the skin has a remarkable capacity for regeneration; during aging or specific pathologies such as diabetes, however, this reparative capacity becomes impaired and can lead to chronic wounds and decreased quality of life. In our current market, the number of agents that have documented ability to enhance brain repair or wound healing is minimal and there is an increased need for new therapeutic approaches.

We hope to bring our drugs to the clinic as novel therapeutic candidates. In this regard, we are working closely with The Hospital for Sick Children and the Centre for Commercialization of Regenerative Medicine to make the translation of our work possible, and furthermore, to potentially move into human clinical trials for brain injury and chronic wound care.

What do you think is the future of drug rescue and repurposing?

We think drug repurposing will grow in importance over the years—primarily because it is significantly less expensive and it takes a shorter time to repurpose than to develop a drug the traditional way. For example, the drugs that we use are all drugs that are already safely being used in humans. This means we do not have to undergo toxicity tests or FDA approvals before they are released to the market.

Sibel Naska, PhD
Research Associate,
Freda Miller’s lab
Developmental and Stem Cell Biology
The Hospital for Sick Children

Freda Miller, PhD
Senior Scientist,
Developmental and Stem Cell Biology
The Hospital for Sick Children
Professor, Department of Molecular Genetics
University of Toronto
Canada Research Chair in Developmental Neurobiology
Howard Hughes Medical Institute International Research Scholar