Somatic Gene Therapy

phenilketonuria, in which the body’s genetic inability to metabolize phenylalanine is treated by eliminating this amino acid from the environment. Such therapies are effective for some inborn errors of metabolism but not others, as described else where in this volume. In contrast, organ transplantation seeks to alter the body’s inherent (genetic) incapacity by replacing cells or organs which are genetically defective with a normal graft. While organ transplantation may be effective for many inborn errors of metabolism, the clinical risk and costs associated with transplantation have made this an uncommon therapy.a

Somatic gene therapy for an inborn error of metabolism is directed at altering the intrinsic metabolic capacity of the body and modifying the genetic component of the disease. Gene therapy involves the use of genes as therapeutic molecules wich may be introduced into the body to provide function necessarry to preserve health or treat disease. In the case of most inborn errors of metabolism, in wich the inheritance of abnormal alleles for an essential enzyme leads to deficiency of certain metabolic function, the purpose of somatic gene therapy is to introduce into the body a copy of gene capable of expressing the essential enzyme and restoring the requisite metabolic function.

The process of gene therapy involves identivying and cloning genes involved in inherited metabolic disease, introducing these genes into the prover cell within the body where the metabolic function is required, and controlling the expression of the gene within therapeutic and save levels. With the progress of the human genome project, genes for most inborn errors of metabolism have been, or arbeing, identified. Many different methods have been described for introducing genes into the body, and gene therapy has been performed successfully in many animal models of inherited disease. Clinical trials are currently underway for several model disorders, including adenosine deaminase deficiency, familial hypercholesterolemia, cystic fibrosis, and gaucher’s disease, and it is likely that clinical trials of gene therapy for other metabolic diseases will be proposed in the next several years.

With the advent of clinical trials, the promise of gene therapy is increasingly assessed against the criteria of real clinical need and clinical practicality. It is likely that gene therapy will become part of routine clinical care for individuals with certain inborn errors of metabolism. For this to haven, however, gene therapies must be effective, save, and superior to conventional pharmaceutical or surgical therapeutic; gene therapies must map to established clinical practice and built on existing clinical expertise, and the methods and products used for gene therapy must be acceptable to physicians, patient, regulatory authorities, and reimburcement agencies. Many methods for gene therapy wich have been proposed my not meet these standards. This chapters reviews the current status of gene therapy in light of the clinical issues which will direct the application and acceptance of this important new technology in clinical practice.