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This book is a brave attempt to discuss the burgeoning field of gene therapy for neurological disorders. To many clinicians, gene therapy has not to date lived up to all the hype and excitement of when it was first suggested. However, as the editors point out in their preface, this has been a little unfair and it remains an exciting area that is worthy not only of intellectual interest but also the possibilities of therapy in the future. The complexities, however, of this technique, cannot be overestimated. Neurons are postmitotic; a brain has a degree of immune privilege by virtue of the blood-brain barrier and other immunological differences to the majority of other organs. The unbelievable complexity of the nervous system makes the “fixing” of any genetic defects incredibly difficult.
The potential uses of gene therapy are not restricted to single gene Mendelian disorders, although it is most likely that this is where the most significant progress will be made. There are more common degenerative diseases, such as Parkinson’s disease and Alzheimer’s disease, where gene therapy can also be considered. In this instance, it is not necessary to correct an identified genetic defect but rather support the dying cells by transfection with genes in coding growth factors and so forth.
All of these issues are discussed in some depth in this book, the first section dealing with the variety of vectors, in particular different viral systems. This is clearly crucial to the problem. As one can imagine, one will need to select an appropriate vector for the problem in hand. If one wants to fix a genetic defect in neurons, then one will need a vector that can effectively transfer the appropriate gene to the appropriate place in the genome, with the appropriate regulatory factors associated, into non-dividing cells. There are emerging vectors that have many if not all of these properties. However, sometimes it will be important to target dividing cells, particularly in tumour disorders, and therefore another vector system will be required. There are a number of important issues as to the construct that is transferred by these vectors. Will the whole gene be necessary? How will the gene, once it is incorporated, be regulated?
Most of the book deals with many of these issues and even discusses rat brain models. The much smaller second part deals with some neurological disorders, with chapters on gene therapy, ischaemic stroke, Parkinson’s disease, Huntington’s disease, pain and lysosomal storage disorders, and gene transfer for CNS regeneration.
This is an interesting book, containing a lot of useful information by some of the world leaders in the field. It sets the scene for potential developments well. However, it quickly moves into the jargon of the field and I think this will limit its accessibility to general neurologists who are not au fait with some of the molecular genetic terminology.