Developing Therapy

Most people don't know how scientists (biomedical investigators) go about developing a treatment for an untreatable disease. We thought it would be a good idea to briefly outline the steps for those interested to learn more about the process. Although the process is super-simplified here, it should be a good starting point:

  1. Finding out what is the basic cause of a disease. In simplest terms, is it environmental or hereditary (i.e. genetic)? Environmental includes diseases caused by diet, habits, some chemical (e.g. lead poisoning), or an infectious agent (e.g. bacteria, virus, etc.). Defective genes that travel from generation to generation cause genetic or hereditary diseases. Most common untreatable disorders are “complex” in what causes them - both environmental and genetic factors may have significant roles in causing these disorders (e.g. various cancers, diabetes, heart disease, etc.). When we are lucky enough to discover that a disease has a single significant cause (e.g. single gene disease), then it is usually easier to move on to the next step in this process.
  2. Develop a model of the disease for further clarifying how the disease causes damage to our body/cells (pathogenesis or pathogenic mechanism), and for testing various therapeutic hypotheses. Disease models can be either cell culture models or animal models. Cell culture models are useful for testing therapeutic hypotheses with therapeutic agents (medicine or drugs) that are available on the market. However, if therapy is expected to be a something not currently on the market, then an animal model would be much better model to test both efficacy (how effective a treatment may be) and safety. Today, thanks to advances in genetic engineering, it is possible to develop genetically modified mouse models of diseases in hopes that the mice will develop symptoms and signs similar to the human disease. Then, the pathogenesis of the disease and possible therapeutic hypotheses can be tested using these potentially life saving mouse models. Both efficacy and safety evidence is needed before investigators and regulatory agencies (e.g. FDA, NIH, CDC, etc.) determine it is reasonable to proceed with experimental clinical trials (i.e. experimental trials on human subjects).
  3. Clinical Therapeutic Trial is divided into the following 4 temporal phases:
  4. Phase I: Primarily for testing safety (usually less than 10 patients enrolled in the trial) and confirming efficacy.
  5. Phase II: For testing efficacy and further testing safety.
  6. Phase III: For large scale testing to further establish how effective or safe a treatment is before presenting it to the market (hundreds of patients may be enrolled in the trial).
  7. Phase IV: Therapeutic use on the market (may involve hundreds of thousands of patients), following which a drug may be pulled off the market if a significant, but rare, side effect is noted.

This process is followed for developing almost any kind of treatment including chemical drugs, gene therapy, or cell therapy. It is now estimated that developing a new drug costs about $800 million, the majority of which is used for clinical trials. So, it is only a wise investment if the potential market for the treatment is huge (i.e. millions). Thus many scientists both in private and public sectors work hard to develop treatments for conditions affecting millions, regardless of the seriousness of the disease or if the disease is currently treatable.

On the other hand, developing a treatment for rare/orphan diseases are very slow, even when the disease is devastating and the biomedical technology for developing a treatment is readily available. For rare or orphan disorders, the cost of developing a treatment may never be recovered. There are some limited help available for developing treatments for these rare disorders (e.g. NORD or FDA orphan drug program). However, most biomedical investigators are not very interested because both the funds for research and glory for discovery are quite limited. Interestingly, medical advances in developing treatments for orphan diseases are sometimes spearheaded by those personally affected by the disease.

Ideally, the following considerations would take precedence over potential financial return:

  1. Is the disease currently treatable?
  2. How promising is the therapeutic hypothesis considering current technology?
  3. How debilitating is the disease if left untreated?
  4. Lastly, how many people are affected?

Considering that only a few hundred IBM2 patients are known worldwide, it is reasonable to expect slow research progress. Nevertheless, we believe it is possible to develop an effective intervention for IBM2 with current medical technology.