17 Aug HCN2: A Gene That Impacts Chronic Nerve Pain May Have Been Discovered…

There has been a great deal of mainstream media attention around the potential for “genetic engineering” to assist in the treatment of chronic diseases.  In fact, just within the last month, there have been articles in both the New York Times and Wall Street Journal, summarizing a relatively novel and exciting technology referred to as CRISPR.

The field of “genetic engineering” is geared toward manipulating the source code of human life our “DNA.”  By altering DNA, scientists can then directly modify proteins, biochemical processes, and living tissues, along with an organism’s growth and function.

One of the main challenges within the field of genetic modification; is making certain that only the targeted problem gene(s) is being altered.  If non-targeted genes are changed during gene editing, horrific consequences can occur such as cancer and death.  

CRISPR apparently represents a clear technological advancement in this regard.  It is cheap to manufacture, easy to work with, highly reproducible, and very specific at splicing (cutting out or modifying) problem genes. CRISPR is part of the way bacteria defend themselves against actual attacks from Virus’s called bacteriophages.  These virus’s that specifically infect bacteria are everywhere, and as a result bacteria, in order to survive, have developed their own defense mechanism.  Genetic engineers, most notably, Dr. Jennifer Doudna, out of the University of California- Berkley, along with her team and colleagues, have reengineered the CRISPR-CAS-9 system to splice out (cut-out) or modify damaged DNA.

This new technology has brought on increased scrutiny with regard to the moral and ethical consideration of DNA manipulation.  DNA is the scientific foundation of life and creation, and it carries the instructions for normal development.  Any modification in those instructions can lead to disease or unwanted consequences.  Gene editing also has come under fire for its potential to exponential impact the normal and slower process of natural selection.  There has also been much ballyhoo about the notion of “designer babies,” and what this might mean for humanity.

As a disease model, a number of devastating illnesses can be traced back to a single “base pair” change within a single gene.  Don’t get to hung-up on the details here. However, to provide perspective, humans have an estimated 25,000 genes and there are over 3 billion “base pairs.”  To think that out of 3 billion “base pairings,” it simply takes a single change, to create disease is frankly astounding.  Some cancers are a product of a spontaneous change (mutation) in our source code “DNA.” This change then leads to uncontrolled expression of a protein and a tumor.

The field of genetic engineering and this new CRISPR technology, in concert with a report out of the University of Cambridge, has laid the foundation for hope and a potential novel future therapy for chronic nerve “neuropathic” related pain.

Within the Cambridge report they have identified a gene referred to as HCN2.  It appears that the HCN2 gene, is expressed in pain-sensitive nerve endings, and that it may regulate the frequency of electrical activity in pain-sensitive nerves and our experience of pain.  Scientists were able to engineer the removal of this HCN2 gene from pain-sensitive nerves and even tested their hypothesis on mice.  

The results indicated that by deleting the HCN2 gene, chronic nerve pain was eliminated.  In addition and importantly, normal pain sensation was not effected.  The ability to preserve normal pain sensation is critical.  For example, imagine if in the process of editing a malfunctioning pain gene; we also lost the ability to feel pain when we encountered something that is scalding, like the fire over a stove.

Perhaps one day soon, we as physicians and patients, will have the tools to simply knock out a specific pain gene like H2N2. And thereby alter the condition of those experiencing chronic nerve pain.  The future seems bright!