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Many biotechs in the CFTR restoration space
Apr 22nd, 2010 by Tom

There are a number of biotechs out there looking at disease modifying drugs for CF.  All seem to be well behind Vertex but will have substantially improved options over what Vertex will hopefully be bringing to the market in the next couple of years.

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One such company getting little press in this area is Galapagos.  They started working with the CFFT in 2005 and discovered 19 targets.  They are now working to refine the best options into a single small molecule to be ready for clinical trials within the next 3 years.  Seems like such a long time.  This is were the difference between software development and drug development becomes very apparent.  Software is always put out years before it is “perfected” and many versions make it to market before it finally becomes solid.  Pharmaceuticals can’t follow the same business practice.  Still, it’s hard to accept that it will take another decade or so before drastically improved therapies make it to market.

More info on Galapagos: Galapagos to build cystic fibrosis drug pipeline

By combining molecules that potentiate the channel activity independently, it is possible to attain therapeutic results in Cystic Fibrosis
Apr 21st, 2010 by Tom

Every time I read an article like this (Potentiation of disease-associated CFTR mutants by hydrolyzable ATP analogs) on PubMed, I realize how far we have to go still.  Trying to keep a positive attitude, it is exciting to see that it is possible to combine multiple compounds and get up to a 36 fold improvement in gating for the G551D defect and almost a 20 fold improvement in gating for the DF508 defect.  For all of those dealing with rarer defects such as A455E that do not have much of a problem functioning once at the cell surface, it would be nice to see how these compounds behave.

Infliximab Successfully Treats Cystic Fibrosis And Crohn's Disease
Apr 20th, 2010 by Tom

There have been several articles about how Infliximab has been used to treat CF and Crohn’s Disease.  Unfortunately, all the articles are the same and provide very little detail on what was treated.  The indication is that the anti-TNF alpha (anti-tumor necrosis factor alpha) antibody reduces the notorious lung inflammation.  But how does this correlate to “successfully treated”?  Did the one patient have improved PFTs?  Did the rate of decline change significantly for this one patient?  What impact did this have on infections? The fact that TNF alpha inhibitors (including Infliximab) can cause latent Mycobacterium Tuberculosis to become active Tuberculosis concerns me.

Full article: Infliximab Successfully Treats Cystic Fibrosis And Crohn’s Disease

Gallium could make a big difference in treating Cystic Fibrosis lung infections
Apr 19th, 2010 by Tom

There’s been a lot in the news over the last year about iron chelators assisting in the treatment of lung infections and breaking up biofilms so I thought it was pretty interesting to see the phase I trial of Ganite (Gallium Nitrate) show up a few weeks back.  Gallium is not an iron chelator but it does interfere with how iron is processed by cells (including bacteria): “Gallium is known to interfere with certain iron-dependent metabolic processes, which can be lethal to single-cell organisms such as bacteria, mycobacteria (e.g., tuberculosis), protozoa (e.g., malaria), and fungi”

Even more interesting is the article in MarketWatch that provides a success story on the use of Ganite along with more info on the trial:
Genta Presents Initial Clinical Data on Use of Gallium Compounds as Treatment for Serious Infections


The one thing I really didn’t like reading in this article was the end of this section: “These data show that gallium is preferentially concentrated in sputum of infected lungs,” said Dr. Raymond P. Warrell, Jr., Genta’s Chief Executive Officer. “High levels were achieved and sustained during short courses of treatment – an especially promising result that should obviate any need to consider direct inhalation”

Does each treatment take 5 days on IV?  If so then an inhaled form would be desired.  The other alternative is the oral version of Gallium.  This however is still preclinical and would be some time, if ever, before available.  Finally, considering the young age of the CF population, the therapeutic seems like it would be best in an inhaled form.

Either way, it’s encouraging to see another potential tool to fight infections, especially highly drug resistant ones, enter clinical trials.

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