Gene Therapy For CPPS
On a public newsgroup, Dr Dimitrakov commented:
Often if you look at the genetic make-up of the person, you can get to the root of [CP/CPPS]. Actually, I have found that patients who come to see me and get tested for Nerve Growth Factor (NGF) gene defects benefit from monoclonal antibodies aimed at NGF (and yes, this is a CURE, not a myth). Unfortunately, this is done only on people from where I practice and not on men travelling to see me. Genetic treatment is etiologic treatment. It is not experimental since it has been shown to work on women with IC from the Pittsburgh group who are down-regulating the Substance P gene using vectors. I have been doing the same with several other genes and although I have only 10 patients so far, the results are promising. Patients never come back for treatment and I have to call them back every month to see how they are doing. It's twelve months now and they are all fine - great for them! Maybe the genetic cure of CPPS is not so far away. (June 2002)
Potential Targets for Gene Therapy in Pain Management
By Jordan Dimitrakov, MD PhD
Assuming that an ideal gene delivery system is available, viral or otherwise, what would be the therapeutic target? Of the many targets comprising the complex nociceptive cascade, how does one choose the best point for therapeutic intervention?
An ideal target should have :
- a well-defined role in the pathogenesis of neuropathic (CPPS) pain,
- a well-defined pharmacologic profile with
specific pharmacologic tools (i.e., agonists and antagonists)
available (similar to what we have in terms of alpha-agonists
and alpha-blockers), and
little role in normal physiology, thus limiting the chances of side effects associated with pharmacologic manipulation of the target.
No consensus exists on such an ideal target for management of pain.
Targets that lend themselves to a genetic approach to pain management should have strong evidence for a role in nociception, a reasonably defined molecular biology and function, and antisense knockdown and knockout data.
Below we will try to address several traditional and obvious targets, such as opioid and a2-adrenergic receptors, and some potentially promising targets, including N-type calcium channels, voltage-gated Ca2+ channels, adenosine triphosphate–sensing purinergic P2 X3, acid-sensing ion channel, and neurotrophin receptors.
In the following sections, we review selected central nervous system (CNS) targets for gene therapy, with particular attention to the evidence of role in nociception, information on the molecular biology, and studies investigating a gene therapeutic approach in altering nociception. Molecular biologic information, including the size of the cDNA encoding the target protein and genomic structure, are critical in designing concrete strategies for gene therapy using viral vectors or oligodeoxyribonucleotides (ODNs).
[work in progress, to be continued ....... ]