New and emerging therapeutic interventions for sight loss conditions are developed by a process called “bench to bedside”, where scientific discoveries in the laboratory (“bench”) move to treatments in the clinic (“bedside”).
There are three main stages in this process – basic research, translational research and clinical research.
Each stage addresses different but important questions. The final stage of the journey is regulatory approval of a therapy for use in people. This journey from start to finish can take decades.
The “bench to bedside” is not always a one-way journey and is in fact often more cyclical in nature. For example, results from clinical research studies can re-inform basic research and ignite the process once again. However, to reach the end goal of an approved therapy will always rely on strong working relationships between scientists, the clinical community and patients.
It can be beneficial to think of research as a road-trip. It’s a journey where researchers need to know where they’re going, what route they will take and how they’re going to get there. The various stages of this journey rely very much on the previous steps to ensure that wrong turns are avoided and that researchers successfully arrive at their chosen destination. Many people with many different roles are needed throughout this journey – Fighting Blindness
Development of a therapy usually starts in a laboratory with basic research, also called “curiosity-driven” or “discovery-based” research. Basic research seeks to understand how our body works when healthy. For example, how the retinal cells are formed in early life, and function in an adult. It also aims to identify why, in disease, cells do not work properly – leading to vision loss. Basic scientists want to find out if the body can naturally fight untimely cell death and degeneration.
For example, what is role of the patient’s immune system in age-related macular degeneration (AMD)? In summary, scientists conduct basic research to increase our knowledge about a condition, to develop theories about its cause and use that knowledge to design a rational treatment, also known as translational research.
It is critical that we study how disease is established if we truly want to prevent it, cure it or stop it in its tracks. So when we study the mechanisms of disease we are researching the underlying cause or process that establishes or triggers the disease. And with each new piece of information generated through research we gain a greater understanding of how a disease process works. – Dr Sarah Doyle, Fighting Blindness funded researcher
Examples of basic research studies
Fighting Blindness recognise that basic research is critical to increase understanding of sight loss conditions and to develop ways that they can be treated or cured.
One example of basic research is examining a person’s DNA (sequencing or genotyping) to search for gene mutations which cause sight loss. In this way, researchers discover the genetic underpinning of the condition and then use this information to identify new targets for therapy. The Fighting Blindness Target 5000 programme is funding scientists in Ireland and the Netherlands to find the genetic mutations that cause inherited retinal degenerations such as Stargardt disease and Usher Syndrome. To learn more about these gene-discovery projects, please see Application of next generation sequencing for the genetic characterisation of Irish retinal degeneration patients.
Another funded researcher, Dr Sarah Doyle is undertaking critical basic research to identify if a protein called SARM1 plays a role in retinal degeneration. Dr Doyle’s team at Trinity College Dublin have previously studied this molecule and have shown that it plays a role in triggering the death of cells in the brain. As the retina is an extension of the nervous system, Dr Doyle and her team seek to identify whether this molecule also has an important function in retinal cell death.
Translational research is defined by The National Institutes of Health (NIH) as “the process of applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease”. Translational research aims to positively impact the healthcare of the sight loss community. When researchers discover a potential intervention that they believe could lead to a treatment, they first need to validate their theory. Using cell or animal models of disease, researchers determine if the proposed intervention is both safe and effective. For safety reasons, this is extremely important before being tested on humans.
With the roadmap that basic research provides, researchers have direction and momentum to translate and progess this knowledge into therapeutic benefit for patient communities. – Fighting Blindness
Examples of translational research studies
Fighting Blindness recognises that translational research is critically important to our goal of building a greater understanding and improving diagnostic, therapeutic and management options for sight loss conditions.
One of our funded researchers, Ms Rebecca Ward at University College Dublin is conducting important translational research, examining neuroprotectant drugs which have the potential to slow photoreceptor cell death in inherited retinal degenerations. Rebecca’s work expands on the investigational basic research being carried out by Professor Breandan Kennedy to identify which neuroprotectant drugs could provide new therapeutic options for inherited retinal degenerations.
A recently completed Fighting Blindness project led by Prof. Tom Cotter in University College Cork (UCC) focused on understanding the mechanism of photoreceptor cell death in retinal degenerations. The Cotter lab demonstrated that Norgestrel (the active compound of the oral contraceptive “minipill”) has a protective effect on photoreceptor cells, slowing their death and maintaining vision.
Clinical trials are medical research studies in which people volunteer to participate. Building on positive observations in the laboratory, clinical trials study the safety and effectiveness of a new procedure, drug or technology in humans. As such, carefully conducted clinical trials are the safest and fastest way to find treatments that work in humans.
If an intervention successfully completes all clinical trial stages, pharmaceutical companies will seek regulatory approval from regulators such as the Food and Drug Authority (FDA) in the USA and European Medicines Agency (EMA) so that their treatment can be licensed for use in particular countries.