How gene profiling in emphysema is helping to find a cure

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States and is thought to affect almost three million people in the UK. New research published in BioMed Central's open access journal Genome Medicine has identified genes whose activity is altered with increasing lung damage and, using a database of drug effects on gene activity (the Connectivity Map), finds that the compound Gly-His-Lys (GHK) affects the activity of these genes. When tested on human cells from lungs damaged by emphysema, GHK was able to restore normal gene activity and repair cell function.

The strongest cause of COPD is smoking, and at least 25% of smokers will develop this disease. Tobacco smoke and other irritants cause oxidative stress and , which over time results in emphysema, the destruction of lung alveolar cells. Without these cells, the lungs are not able to efficiently exchange oxygen for carbon dioxide, leaving the patient continuously short of breath and with low levels of oxygen in their blood.

In a ground breaking, multi-centre, study funded by the National Institute of Health (NIH), researchers used cells taken from lungs donated by patients undergoing double lung transplant, whose own lungs were irrevocably damaged by COPD. Profiling of these samples showed that 127 genes had changes in activity that was associated with worsening within the lung. As would be expected from the nature of the disease, several genes associated with inflammation, such as the genes involved in signalling to B-cells (the which make antibodies), showed increased activity.

In contrast genes involved in maintaining and normal , along with the growth factors TGFβ and VEGF, were down-regulated and showed decreased activity. This included genes which control the ability of the cells to stick together (cell adhesion), produce the which normally surrounds the cells, and which promote the normal association between lung cells and blood vessels.

Dr Avrum Spira and Dr Marc Lenburg, who co-led this study from the Boston University School of Medicine, explained, "When we searched the Connectivity Map database, which is essentially a compendium of experiments that measure the effect of therapeutic compounds on every gene in the genome, we found that how genes were affected by the compound GHK, a drug known since the 1970s, was the complete opposite of what we had seen in the cells damaged by emphysema."

Dr Joshua Campbell explained, "What got us especially excited was that previous studies had shown that GHK could accelerate wound repair when applied to the skin. This made us think that GHK could have potential drug's as a therapy for COPD."

Prof James Hogg, from the University of British Columbia continued, "When we tested GHK on cells from the damaged lungs of smokers with COPD, we saw an improvement in the structure of their actin cytoskeleton and in cell adhesion, especially to collagen. GHK also restored the ability of cells to reorganise themselves to repair wounds and construct the contractile filaments essential for alveolar function."

GHK is a natural peptide found in human plasma, but the amount present decreases with age. While more testing needs to be done on its effects in COPD, these early results are very promising. Therapeutic studies with GHK in animal models of COPD are now underway with the ultimate goal of moving this compound into clinical trials. As more signatures are discovered, this method of matching drug to disease may provide a rapid method for discovering potential uses for existing drugs and compounds.

More information: A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK Joshua D Campbell, John E McDonough, Julie E Zeskind, Tillie L Hackett, Dmitri V Pechkovsky, Corry-Anke Brandsma, Masaru Suzuki, John V Gosselink, Gang Liu, Yuriy O Alekseyev, Ji Xiao, Xiaohui Zhang, Shizu Hayashi, Joel D Cooper, Wim Timens, Dirkje S Postma, Darryl A Knight, Marc E Lenburg, James C Hogg and Avrum Spira Genome Medicine (Section: Molecular genetics, genomics & epigenetics of disease) (in press)

add to favorites email to friend print save as pdf

Related Stories

Reversing smoke-induced damage and disease in the lung

Oct 13, 2011

By studying mice exposed to tobacco smoke for a period of months, researchers have new insight into how emphysema and chronic obstructive pulmonary disease (COPD) develops. In the October 14th issue of Cell they also report ...

Body's defenses may worsen chronic lung diseases in smokers

Feb 09, 2009

Although the immune system is designed to protect the body from harm, it may actually worsen one of the most difficult-to-treat respiratory diseases: chronic obstructive pulmonary disorder (COPD), according to new University ...

Recommended for you

Science of romantic relationships includes gene factor

Nov 23, 2014

(Medical Xpress)—Adolescents worry about passing tests, winning games, lost phones, fractured bones—and whether or not they will ever really fall in love. Three Chinese researchers have focused on that ...

Stress reaction may be in your dad's DNA, study finds

Nov 21, 2014

Stress in this generation could mean resilience in the next, a new study suggests. Male mice subjected to unpredictable stressors produced offspring that showed more flexible coping strategies when under ...

More genetic clues found in a severe food allergy

Nov 21, 2014

Scientists have identified four new genes associated with the severe food allergy eosinophilic esophagitis (EoE). Because the genes appear to have roles in other allergic diseases and in inflammation, the ...

Brain-dwelling worm in UK man's head sequenced

Nov 20, 2014

For the first time, the genome of a rarely seen tapeworm has been sequenced. The genetic information of this invasive parasite, which lived for four years in a UK resident's brain, offers new opportunities ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.