Why do stroke regenerative therapies fail to reach the clinic?

Author: Samantha Payne, 03/07/17

Dale Corbett, University of Ottawa (photo used with permission)

The author of the popular Seven Habits of Highly Effective People book, Steven R. Covery, said “strength lies in differences, not in similarities.” While this may be helpful advice for improving your personal life, researchers are learning that differences in preclinical studies are weakening the ability to translate effective therapies to the clinic.

While one might assume that it is beneficial to have diversity in the way research is conducted, it has been demonstrated that inconsistencies between preclinical studies actually leads to the failure of treatments in clinical trials that were shown to work in preclinical animal models.

Considering the staggering amount of time (estimated to be 17 years on average!) and resources that go into seeing a therapy into clinical trials, it is imperative that promising therapies are backed by plenty of evidence-based translational research. For example, when a researcher is designing a study, there should be standard practices and guidelines that are followed. Without these basic requirements, differences in study designs (like animal model used, or outcomes measured) makes it difficult to draw conclusions within the body of literature and limits translation into clinical therapies.

February was Heart and Stroke Awareness Month and it inspired me to highlight this problem in regenerative therapies to treat stroke. Current clinically available stroke therapies can only alleviate patient symptoms, and are unable to stimulate regeneration of brain tissue for long-term recovery. To address this, researchers are investigating regenerative medicine strategies such as cell transplantation and drug delivery but, to-date, there has been limited translation to clinical trials.

Dr. Dale Corbett, professor of the Brain and Mind Research Institute at the University of Ottawa and Chair of the Heart and Stroke Foundation, graciously agreed to answer a few of my questions about this issue:

Why is it important that preclinical stroke studies adhere to standard practices?

Over the past two decades, many standard or “best” practices in preclinical stroke research have been identified. Many of these concepts have come from painful and costly mistakes. For example, in stroke neuroprotection studies we learned that many of the drugs that were used had unintended “hypothermic actions” that in and of itself were neuroprotective. When the hypothermia was controlled, the drugs lost their protective effects. Some interventions delay cell death, but if survival is extended the cells eventually die.

Flawed preclinical studies, such as these, resulted in dozens of drugs entering clinical trials where ultimately all of them failed. Much of this could have been prevented had preclinical scientists had a set of agreed upon best practices to follow. We must ensure that going forward we don’t continue to make the same errors.

What do you think is the most pressing issue that currently needs to be addressed in order to bridge the gap between bench and bedside for stroke?

It is essential to break down the silos that have historically separated preclinical and clinical stroke researchers. There has been little opportunity for these groups to engage in meaningful dialogue. To address this problem, within the Canadian Partnership for Stroke Recovery (CPSR), we have created a multi-day course (Special Program in Neurorecovery, SPiN) that brings basic and clinical trainees together to learn first-hand about their respective approaches through lab and clinical rehabilitation visits and demonstrations. This helps to foster mutual respect and a better understanding of how each other’s research can contribute to advance knowledge to ultimately improve the lives of those living with stroke. At CPSR, we do everything we can to bring clinicians and basic scientists together including panel discussions and debates at scientific meetings and collaborative research projects.

The first ever Stroke Rehabilitation and Recovery Roundtable (SRRR) meeting, where leading stroke experts came together to develop a consensus on the treatment of stroke, was held last May. Since then, have you seen any other examples of progress towards this goal?

It is still early days, but many investigators are now following this project using social media. The consensus papers have been submitted for co-publication in leading stroke journals, a paper defining common terms often used in different ways by investigators in the field is about to be submitted for publication and several of the SRRR members are preparing presentations for major scientific conferences (e.g. European Stroke Organization Conference) where the goals of the SRRR will be highlighted.

Can you recommend some simple steps that researchers involved in preclinical work could take to ensure that their experimental design is consistent with what is required for clinical translation?

Learn as much as you can about the clinical side of stroke. This will help you ask more meaningful questions and design better experiments that have greater potential for translational success.

  1. Engage a clinician and express your interest in visiting a stroke facility; 2) Find a local stroke survivors group, attend their meetings, offer to give a talk about your research – much can be learned from listening to patients’ stories about their experience with stroke; 3) Seek out a suitable clinician to be on your thesis supervisory committee; 4) Read clinical stroke papers in journals such as Stroke or Neurorehabilitation and Neural Repair; 5) Attend stroke meetings where there is a strong clinical research presence (e.g. Canadian Stroke Congress); and, 6) attend a course such as SPiN!

With leaders such as Dr. Corbett helping to guide preclinical studies, we can take action to mitigate clinical failure of treatments and ensure that stroke research groups around the world are working together towards a common goal.

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Samantha Payne

Samantha Payne

Samantha is a PhD student in the Chemical Engineering and Applied Chemistry department at the University of Toronto. She has previously investigated regeneration in a non-mammalian gecko model during an MSc program, and now currently combines stem cell biology and biomaterials to encapsulate and deliver therapeutic cells to the stroke-injured brain. Samantha became interested in scientific communication as a means to combine her love of writing and science to share exciting scientific discoveries to a broader community. Follow Samantha on Twitter @samantha_lpayne
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