Surprise drug may stop asthma

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Great news. Could play a role for CFS as well.

http://sciencealert.com.au/news/20132701-24000.html

UNSW researchers have developed a compound that has had a surprise result: being effective in the prevention of asthma.

The compound was originally developed to treat leukaemia. The research, led by the University of Newcastle, has been published in Nature Medicine. It centres on the role played by two proteins in the lungs in causing asthma attacks.
When they come into contact with the common cold virus and dust mites, the two main asthma triggers, they work together to produce a series of events that cause an attack.
The research shows that the UNSW-developed compound is able to activate a protein that is suppressed during asthma. This could mean that in the future doctors would be able to treat the cause of asthma, not just the symptoms.

“Asthma is one of the major diseases of the developed world. It’s very rare to find a compound that can reverse the symptoms of asthma,” says Dr Anthony Don, who started working on the compound in the treatment of acute myeloid leukaemia.
“The important thing with this compound is that it’s not just alleviating the symptoms, it’s hitting at an underlying disease mechanism,” says Dr Don, a team leader at UNSW’s Lowy Cancer Research Centre.

Associate Professor Jonathan Morris from the School of Chemistry synthesized the compound.
The development is also significant because asthma attacks are currently treated similiarly regardless of whether they are caused by viruses or allergens, but virus-induced effects are much less responsive to current therapies.
The compound could also be used in the treatment of other inflammatory diseases.


http://www.ncbi.nlm.nih.gov/pubmed/23334847

The compound they used was a "nonphosphorylatable FTY720 analog".

 

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http://www.ncbi.nlm.nih.gov/pubmed/21767261

Abstract

Cancer cells are hypersensitive to nutrient limitation because oncogenes constitutively drive glycolytic and TCA (tricarboxylic acid) cycle intermediates into biosynthetic pathways. As the anaplerotic reactions that replace these intermediates are fueled by imported nutrients, the cancer cell's ability to generate ATP becomes compromised under nutrient-limiting conditions. In addition, most cancer cells have defects in autophagy, the catabolic process that provides nutrients from internal sources when external nutrients are unavailable. Normal cells, in contrast, can adapt to the nutrient stress that kills cancer cells by becoming quiescent and catabolic. In the present study we show that FTY720, a water-soluble sphingolipid drug that is effective in many animal cancer models, selectively starves cancer cells to death by down-regulating nutrient transporter proteins. Consistent with a bioenergetic mechanism of action, FTY720 induced homoeostatic autophagy. Cells were protected from FTY720 by cell-permeant nutrients or by reducing nutrient demand, but blocking apoptosis was ineffective. Importantly, AAL-149, a FTY720 analogue that lacks FTY720's dose-limiting toxicity, also triggered transporter loss and killed patient-derived leukaemias while sparing cells isolated from normal donors. As they target the metabolic profile of cancer cells rather than specific oncogenic mutations, FTY720 analogues such as AAL-149 should be effective against many different tumour types, particularly in combination with drugs that inhibit autophagy.
© The Authors Journal compilation © 2011 Biochemical Society

 

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http://circres.ahajournals.org/content/96/8/913.full

Accordingly, the nonphosphorylatable chiral analogue of FTY720, AAL149, had no effect on vasodilation(and did not increase endothelial permeability).