Progress in cystic fibrosis

Researchers in California have discovered a way to partially repair damaged lung cells from patients with cystic fibrosis, an inherited disease that affects more than 70,000 people around the world. The results are published in the journal Nature Chemical Biology this week, led by Professor William Balch and his team at the Scripps Research Institute.

It all centres on protein processing - when proteins are made in our cells, they are folded up into the correct shape. But if there's a fault in the protein, or in the folding process, then the protein doesn't work properly and it gets broken down again. 

In cystic fibrosis, the disease is caused by faults in the gene that makes a protein called CFTR, which normally sits on the surface of cells and helps to shuttle salts across the cell membrane. Around nine out of ten people with the disease have a faulty version of the CFTR known as DF508 CFTR. The resulting protein is the wrong shape, and gets broken down in the cell's endoplasmic reticulum - the molecular factory where proteins are made.

The researchers figured that if they could stop the DF508 version of the protein being degraded, then it might work at least a bit, and help to relieve some of the symptoms of cystic fibrosis - and that's just what they've managed to do.

The scientists used a drug called suberoylanilide hydroxamic acid, or SAHA for short, which blocks enzymes called histone deacetylases. These normally work to affect the proteins that package DNA in the nucleus of the cell, helping to switch genes on and off, but they also have other effects on the processing of proteins.

They tested the drug on lung cells taken from cystic fibrosis patients with the DF508 fault,  and found that SAHA treatment restored the level of CFTR activity to 28 per cent of that found in normal lung cells.

That may not sound like a lot, but it could make a real difference. For example, patients with less severe cystic fibrosis, with around 15 to 30 per cent levels of CFTR activity, can lead a much more normal lifestyle, compared with people carrying a more severe fault like DF508.  So being able to restore 28 per cent of lung cell function could really be significant.

The scientists also found that SAHA works best at relatively low doses, which is important if it's to be taken forward for clinical trials. The other good thing about the drug is that it has already been used in clinical trials for treating cancer, but in higher doses over a short period of time.

More research and tests need to be done to find out if it's suitable for giving in lower doses over a lifetime, which would be the case for treating people with cystic fibrosis. But these early results are certainly promising. And Balch thinks that a similar approach might also work for other conditions such as type II diabetes, arthritis, osteoporosis, and Alzheimer's disease.