Thursday, June 26, 2014

Rare Diseases and Common Diseases can Converge to the Same Clinical Conditions

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

Here is a short excerpt from Chapter 10.

As applied to diseases, convergence occurs when different genes, cellular events, exposures, and pathogenetic mechanisms all lead to a similar clinical phenotype. Convergence is found in common diseases and in rare diseases. In the case of systemic responses to injury, convergence may have an evolutionary origin. For example, humans have evolved to respond in an orchestrated way to a variety of pathologic stimuli. Various antigens can stimulate an orchestrated acute allergic response that may be identical for a wide variety of antigens (hives, bronchial constriction, puffy eyes). Likewise, humans have evolved to a systemic response to local infection that is specific for our species [7]. Convergence is observed in all the rare diseases that have genetic heterogeneity, either allelic heterogeneity or locus heterogeneity (see Section 9.3). In these cases, many underlying genetic causes yield the same clinical phenotype.

10.1.2 Rule—Regardless of the path taken, many pathologic processes will converge to the same pathologic condition.
Brief Rationale—There are a limited number of ways that the body can respond to malfunctions.

Think about all the things that can go wrong with your car. The engine can stop, the fuel system can be interrupted, the battery may die, the brakes may fail, any of the four tires can flatten, the headlights may not work, the electrical system may suffer a circuit shortage, and so on. It seems like a long list, but it is not. Maybe a dozen common problems account for the vast majority of car problems. Add these to a few dozen less likely problems, and you have a listing that would cover 99% of automobile repair issues. Every auto repairman knows that there are a limited number of systems in the car that can go bad. Repairs are relatively easy if the repairman can determine the system or part that is at fault. Whereas the number of different auto problems is limited, the number of events that can lead to these problems is virtually infinite. An auto repairman knows that for every engine breakdown, there might be thousands of possible causes. A non-functioning engine can be corrected by taking out the bad engine and putting in a new engine. If he is a very good repairman, he will determine whether a problem in a different system (e.g., the fuel injector) was indirectly responsible for the engine failure. Diagnostic tools should determine when a defect in one system is responsible for a defect in another system. Humans, like automobiles, are highly complex. Nonetheless, there are a limited number of problems that can occur in a complex organism. Heart attacks exemplify pathological convergence. Many different pathological processes can lead to the blockage of a coronary artery, such as: atherosclerotic plaque, hypertrophy of the arterial wall, spasms of the artery, acute infection of the artery, thrombus formation within the artery, arterial tear or dissection, developmental defects resulting in narrowing. Genes and environment contribute to these mechanisms. In the end, they can all produce one clinical phenotype; the all-too-common heart attack.

In chapter 10, we explore disease convergence, and explain why rare diseases and common diseases may sometimes converge to the same clinical phenotype. In many cases, treatments developed for a rare disease will be effective against a common disease that shares its convergent pathway (example, rare causes of hypertension and common causes of hypertension all responding to to the same treatment regimens).

I urge you to read more about this book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy for your library or reading room.

- Jules J. Berman, Ph.D., M.D.

tags: rare disease, rare disease research, rare diseases, orphan diseases, orphan drugs, drug development, common diseases, complex diseases, rare disease models of common diseases