Progress toward therapies: Path to the Clinic
The path from a basic discovery to a new therapy goes through some typical stages. The first step is the basic research in which scientists learn fundamental information about stem cells, such as how to mature stem cells into cells that could repair spinal cord injury or produce insulin to treat diabetes, or understanding the normal environment of a stem cell in the body.
The next phase of research is often called translational research. This is the step when scientists take that initial discovery—the ability to mature an embryonic stem cell into a therapeutically useful cell type, for example—and start learning how it could be turned into a therapy. Some of CIRM’s translational awards focus on developing animal models for testing stem cell therapies or creating stem cell models in a lab dish to find drugs that treat Parkinson’s disease or autism. These awards are expected to result in a proof of concept for a future therapy, such as a potential drug or a cell type that might prove useful in treating a disease.
In the next phase of research, scientists take that proof of concept and show that it could really work—at least in animals. This is often called the preclinical phase. During preclinical research scientists identify what’s called a development candidate, which is the exact cell or molecule that the team intends to turn into a therapy.
After finding a development candidate, scientists collect data to show the Food and Drug Administration that their candidate is safe enough to try in humans. Collecting this much data is extremely expensive and is frequently not funded by governmental agencies such as the NIH. CIRM has invested heavily in this stage with the understanding that there can be no clinical trials and no therapies if research groups can’t collect the safety data they need to begin a clinical trial. This FDA filing is called the investigational new drug application (IND).
The basic research, translational work and preclinical data collection are just the lead up to a clinical trial. Once the first phase of a clinical trial begins it takes many more years to prove that a prospective therapy is safe and effective for widespread use. The first phase is intended to test whether a possible therapy is even safe. Remember that until this step the drug or cell has only been tested in animals, which are very different from humans. This phase includes only enough people to verify safety.
Phase II includes slightly more people and also looks at whether the drug or cell is effective at treating the disease or injury. After a phase II study concludes and scientists can show that their approach is both safe and effective, they can start testing their therapy on large numbers of people in a phase III trial. After phase III, the FDA reviews all the data to see if the proposed therapy worked and was safe, then it can be used by doctors throughout the country to treat patients.