By this point in the book, we feel sure you as readers have appreciated the heavy emphasis on diagnostics. In fact, the mainstay of clinical genetics is still in identifying the etiology and pathogenesis of specific disorders. However, as the practice of clinical genetics has progressed, so have advances in therapies. There are now several available modalities of genetic treatments. Up until recently, however, most treatments provided by medical geneticists primarily involved counseling and case management. The treatment of inborn errors of metabolism (IEM) dates back to the mid-1960s. These treatments have involved dietary adjustments, specialized formulas, and vitamin/cofactor supplementation. More recently tissue transplantation and enzyme replacement therapies have become available. New treatment modalities have been developed for non-metabolic disorders. Bioengineered pharmaceuticals are now commonplace. Other treatment options like personalized medicine strategies, tissue cloning, gene correction, and true gene therapy all sit poised for transition out of clinical trials and into standard medical care. In the first section of this chapter we will discuss the mechanisms of the different modes of genetic therapies. In the second section we will discuss the clinical application of these therapies.
Part 1: Background and Systems Integration
What are Genetic Therapies?
In the broadest sense, genetic therapies can include any treatment or medical intervention for genetic disorders. Alternatively, it can include a treatment that uses a genetically based technology regardless of the disease etiology. Thus, one could propose that an aortic replacement surgery for a patient with Marfan syndrome could be classified as a "genetic therapy." Likewise, a monoclonal antibody treatment for cancer or multiple sclerosis might be considered a "genetic therapy." A narrower definition of "gene therapy" would be only those treatments in which there is actual manipulation of the patient's DNA to produce a therapeutic response. For the purposes of this chapter, we will shoot for somewhere in between.
The discipline of clinical genetics began to emerge in the 1960s. The role of the clinical geneticist was primarily diagnostic back then. Genetic testing at that point was largely limited to low resolution (400 band) G-banded chromosome studies and a handful of metabolic tests. Likewise, no molecular therapies existed then. The clinical geneticist functioned primarily as a diagnostician. Beyond diagnostics, the geneticist had a limited number of modalities in which to "treat" the patient. Over time, the type of roles that a geneticist performs has greatly expanded. Currently the majority of clinical geneticists work in a primarily academic environment. Still there are increasing numbers of clinical geneticists in private practice or working as members of single-specialty teams like a large pediatric practice in which they do some pediatrics, but manage the genetic patients for the group.
This has always been a key role of the geneticist. Patients with genetic disorders often have conditions that are rarely ...