What is it and Why Cysteamine for CF?

What is cysteamine?

Cysteamine is a licensed drug used in the treatment of cystinosis for more than 20 years. After a fortuitous observation, laboratory based work suggests that cysteamine may be a beneficial adjunct to conventional antibiotic treatment in CF. Cysteamine is a potent mucolytic, it disrupts biofilms, is antimicrobial, and synergises with other antibiotic agents, broadening their spectrum of activity, and reverses antibiotic resistance (even in multi-drug resistant bacteria). Although the pharmacokinetic characteristics of cysteamine are well established in people with cystinosis, there are no such data for cysteamine in CF.  Recent studies, however, show promise for the use of cysteamine for treating patients with cystic fibrosis.

Why cysteamine for CF?

·         Cysteamine as a mucolytic with antimicrobial properties
Much of the data for cysteamine as a mucolytic comes from Novabiotics’ recent posters and papers on oral-route cysteamine in CF. Their posters from the European Cystic Fibrosis Conference in 2014, especially “Ex vivo efficacy of Lynovex®, a next generation tri-functional candidate cystic fibrosis therapy” demonstrate evidence of great synergy with existing antibiotics when tested on CF sputum, as well as action against biofilms and improved performance compared to existing mucolytics such as Pulmozyme.
A patient on a current genotype-blind trial of Cystagon in CF being run in Aberdeen described her FEV rising from 1.0 to 2.1 in four weeks, with her mucus becoming thin and easy to shift and a greatly improved sense of wellbeing.

·         Cysteamine and Rescue of F508del-CFTR
The European Institute for Research in Cystic Fibrosis recently published an important paper in the journal Autophagy:
In it they describe how, through restoration of autophagy in CF epithelial cells, F508del-CFTR is rescued and then – with the addition of green-tea extract epigallocatechin gallate (EGCG) – maintained at the plasma membrane for a significant period after cysteamine therapy ceased. The researchers conducted a small open-label trial of ten patients homozygous for F508del (study performed at Federico II University, Naples), administering cysteamine (as Cystagon) and EGCG in a phased fashion, including washout.
The treatment effects are listed on page 64 of the accepted manuscript and make for provocative reading. Significant FEV1 increases were observed, typically >10% absolute. Marked drops in sweat chlorides were also seen, with most patients seeing drops of at least 20mmol/L and many seeing their chloride numbers lowered more than half.
These results lead one to believe that patients with at least one copy of F508del-CFTR may benefit from a combined therapy of Cystagon and EGCG.
In the Italian study, Cysteamine bitartrate (trade name Cystagon®, Orphan Europe), oral administration of 150 to 300 mg of cysteamine base every 6 h.  In the Aberdeen study, patients started slowly and worked up to 450 mg 4 times a day (every 6 hours).
Epigallocatechin gallate (EGCG) (trade name Epinerve®, SIFI Pharmaceuticals). 270 mg once daily.

·         Cysteamine as a treatment for fibrotic diseases
One additional benefit of cysteamine in CF is indicated by the claims of this patent http://www.google.com/patents/US20140275279 whose Abstract reads as follows:
“Fibrotic diseases are characterized by the replacement of healthy tissue with scar tissue and extracellular matrix in response to tissue damage. Here we describe the reduction of extracellular matrix (ECM) deposition, interstitial fibroblasts, interstitial volume, expression of Collagen I mRNA and protein, expression of profibrotic cytokines and macrophage infiltration by Cysteamine treatment.”
This is of obvious interest to CF patients, given the fibrosis experienced in the pancreas, along with damage done to lungs, liver and other affected organs.

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