VX-770 Drug Trial moves to Phase 3

[cfmonkey45]

This issue is rather personal to me, because my sister was diagnosed at 3 weeks with Cystic Fibrosis, a terminal genetic disease that is often fatal due to complications (i.e. related diabetes, susceptibility to illnesses and bacteria, as well as common lung collapses and failures in other internal body organs). The disease itself is characterized by a lack of recognition of salt by many cells, leading to very thick mucuousy membranes that form rapidly and build up, clogging many vital organs, including the digestive tract, especially the pancreas and intestines, and specifically the respitory system.

Until the 1990s, the average life expectancy was about 18-25. Now, it's about 35-50.

Now, no less than four clinical drugs are in development, which means that a long-lasting cure is imminent.



Lastly, and most pertinent to debate and discussion here, is the fact that this drug was achieved through reprogramming a cold virus to help lung cells recognize salts, thus lowering the amount of mucuous in the body significantly. Basically, the plot to the 2007 movie "I am Legend", except it doesn't turn everyone into vampire zombies.


http://www.cff.org/aboutCFFoundation...n-Children.cfm

VX-770 Trial Begins in Children as Part of Phase 3 Program
August 5, 2009
Today, the CF Foundation announced the initiation of a clinical trial in children as part of the Phase 3 registration program for VX-770. VX-770 is an investigational oral therapy aimed at treating the underlying cause of cystic fibrosis. The drug is being developed by Vertex Pharmaceuticals with support from the CF Foundation.
This is the second of three clinical trials underway in the Phase 3 registration program for VX-770. The registration program is designed to generate data that the U.S. Food and Drug Administration can use to determine if VX-770 is safe, effective and acceptable for approval.
“This potential drug is one of the most promising therapies in our pipeline that aims to treat the underlying cause of cystic fibrosis,” said Robert J. Beall, Ph.D., president and chief executive officer of the CF Foundation.
“We’re excited that enrollment is open for this second trial. The initiation of this study is an advancement in our efforts to bring a new therapeutic option to CF patients.”
The trial is a two-part study of VX-770 in patients with CF age six to 11 years who have the G551D mutation of CF. It will enroll approximately 30 children with CF.
The first trial, which was initiated in May, is examining VX-770 in people with CF age 12 and older who have the G551D mutation of CF.

http://www.cff.org/research/Clinical...h/FAQs/VX-770/

FAQs About VX-770 and VX-809
Vertex Pharmaceuticals is developing two oral compounds designed to treat the basic defect in cystic fibrosis—a faulty gene and its protein product, called CFTR.
VX-770, the most advanced of the two compounds, is known as a potentiator and is designed to allow CFTR located at the cell surface to function correctly. In 2008, the CF Foundation and Vertex announced positive Phase 2 clinical trial results for patients who have the G551D gene mutation of CF.
VX-770 is currently being evaluated in a Phase 3 registration program that is comprised of three different clinical trials. The registration program is designed to generate data that the U.S. Food and Drug Administration can use to determine if VX-770 is safe, effective and acceptable for approval.
Vertex is also developing VX-809, known as a corrector, which is designed to move defective CFTR to its proper place in the cell.

http://cysticfibrosis.about.com/od/c...101/f/cure.htm

Question: Is There a Cure For Cystic Fibrosis?
Answer: So far, there is no cure for cystic fibrosis but researchers are working hard to find one. Many people believe that someday soon, there will be. We definitely are a lot closer now than ever before. The vast body of research that has been done over the last couple of decades has taught us a lot about cystic fibrosis, given us many new drugs and treatments that have dramatically improved both life expectancy and quality of life, and opened doors to new research that could lead to a cure.
Some of the possible cures being studied:
Gene Therapy

In 1989, the gene responsible for causing cystic fibrosis was discovered. This was an exciting discovery for the CF community. Many believed the discovery would lead to a cure through gene therapy. Unfortunately, that has not happened yet – but not for the lack of trying. Numerous studies have been done to try and correct the genetic defect but none of them have been successful. The biggest problem with gene therapy so far has been finding a vector that can effectively carry the corrected gene to the cells. There may still be hope for gene therapy, though. In July 2009, a group of researchers at the University of North Carolina – Chapel Hill had very good results using a common cold virus as a vector to transfer the gene in laboratory samples of lung tissue. The research team is now working on a way to weaken the cold virus so the treatment can be tested in people with cystic fibrosis.
VX-770

VX-770 is a drug being tested by Vertex Pharmaceuticals in people with cystic fibrosis who have at least one copy of the G551D mutation. The drug may actually be able to target the defect in the CFTR gene and restore its ability to open up chloride channels, thus allowing salt to flow in and out of the cells properly. Unlike gene therapy, VX-770 would not replace the defective gene. Rather, if successful, VX-770 would repair the problem in the existing gene.
VX-809

VX-809 is another drug being tested by Vertex Pharmaceuticals in people who have two copies of the ∆F508-CFTR mutation. It is similar to VX-770 in that it may be able to get salt flowing through the cells properly, but it works a little differently. If it works as researchers hope it will, VX-809 would open chloride channels by moving the CFTR protein to its proper place on the airway cell membrane.
Miglustat

Miglustat is a drug manufactured by Actelion Pharmaceuticals that is already in use to treat other conditions, but it is currently being studied for use in people with cystic fibrosis who have two copies of the ∆F508-CFTR mutation. The study is small scale -- consisting of only 15 participants -- but so far the results have been promising as Migulstat has been able to reverse the CFTR defect and restore normal activity to cells.
Ataluren

Ataluren, which was once called PTC124, is being studied by PTC Therapeutics as a possible cure for people with CF who have nonsense mutations. In nonsense mutations, a piece of “gibberish” code appears amidst the normal code in the CFTR gene. The nonsense code acts like a stop sign, preventing the cells from reading any code that occurs after it. Ataluren may be able to correct that problem by helping the cells to ignore the stop sign and keep reading the code that occurs after it, thus restoring normal function to the cells.
Sources:
C. Norez, F. Antigny, S. Noel, C. Vandebrouck, F. Becq. “A CF Respiratory Epithelial Cell Chronically Treated by Miglustat Acquires a Non-CF Like Phenotype”. American Journal of Respiratory Cell and Molecular Biology. August 2009.
Cystic Fibrosis Foundation. June, 2009. 24 July 2009.
Zhang L, Button B, Gabriel SE, Burkett S, Yan Y, et al. 2009 “CFTR Delivery to 25% of Surface Epithelial Cells Restores Normal Rates of Mucus Transport to Human Cystic Fibrosis Airway Epithelium”. PLoS Biol 7(7): e1000155. doi:10.1371/journal.pbio.1000155. 24 July 2009.

[Adar]

I am very happy to read about this, it seems like they have solved a major problem with gene therapy through retro viruses. Previously there have been one major issue with viral vector treatment. They have caused cancer in many of the people treated (article on such a treatment).

Background: Gene therapy is currently carried out by using retro viruses. A retro virus insert a piece of it's own DNA into the DNA of the infected cell. In normal cases this is done to make the cell create new viruses. Scientists create viruses where they change the inserted sequence into a functional version of the damaged gene. This new functioning gene produce the protein that the damaged gene normally would have produced, it is however located at a different place in the genome than the normal gene. It's the placement of the gene that have been causing us alot of trouble in the last 4 years. Previous attempts have had the gene sometimes being inserted in such places that it have interfered with other genes and caused cancer. I have not been able to find a good description of the virus vector used for this medicine but most likely they have managed to solve this issue by using a virus that always insert it's DNA into the same spot.

Modified retroviruses used for gene therapy are allways going to be less potent than the original virus. The creation of a retrovirus is similar to take a car, remove half the engine and replace it with lead. Therefore we do not need to worry about Will Smith becoming the last human in New York .

[cfmonkey45]

I am very happy to read about this, it seems like they have solved a major problem with gene therapy through retro viruses. Previously there have been one major issue with viral vector treatment. They have caused cancer in many of the people treated (article on such a treatment).

Background: Gene therapy is currently carried out by using retro viruses. A retro virus insert a piece of it's own DNA into the DNA of the infected cell. In normal cases this is done to make the cell create new viruses. Scientists create viruses where they change the inserted sequence into a functional version of the damaged gene. This new functioning gene produce the protein that the damaged gene normally would have produced, it is however located at a different place in the genome than the normal gene. It's the placement of the gene that have been causing us alot of trouble in the last 4 years. Previous attempts have had the gene sometimes being inserted in such places that it have interfered with other genes and caused cancer. I have not been able to find a good description of the virus vector used for this medicine but most likely they have managed to solve this issue by using a virus that always insert it's DNA into the same spot.

Apparently, scientists expect to have completely mapped the human genome by 2015, so hopefully, this drug and others like it will be able to be successfully implemented to help save and prolong lives.


However, despite my glee for this, I do wonder what the long-term consequences for humanity will be if we eliminate diseases. The heterozygous carriers of the Cystic Fibrosis gene have been known to provide immunity against Cholerea (Sickle Cell anemia does the same against malaria as well), something my great uncles are greatful for helping them survive Japanese interment camps in WW2. That, and with the social and evolutionary changes that will accompany a world without diseases.

Modified retroviruses used for gene therapy are allways going to be less potent than the original virus. The creation of a retrovirus is similar to take a car, remove half the engine and replace it with lead. Therefore we do not need to worry about Will Smith becoming the last human in New York .

And miss out on all the huge movie sales?

[Adar]

Apparently, scientists expect to have completely mapped the human genome by 2015, so hopefully, this drug and others like it will be able to be successfully implemented to help save and prolong lives.

We have already mapped the human genome well enough to identify where the faulty virus insertions was inserted. The problem is that previously used viruses have not been specific for where they are integrated into the genome. I.e. we were unable to predict where they would end up. This randomness is in the nature of the virus, thereby forcing us to find new viral viruses which are less random in their integration of DNA. My guess is that these scientists have succesfully achieved this.

However, despite my glee for this, I do wonder what the long-term consequences for humanity will be if we eliminate diseases. The heterozygous carriers of the Cystic Fibrosis gene have been known to provide immunity against Cholerea (Sickle Cell anemia does the same against malaria as well), something my great uncles are greatful for helping them survive Japanese interment camps in WW2. That, and with the social and evolutionary changes that will accompany a world without diseases.

Cool, I did not know that. It is however not a problem, heterozygous carriers are alot more common than homozygous ones. Only homozygous carriers are going to be treated. Thereby allowing all the benefits but avoiding the Cystic Fibrosis.

I am also unsure on how well the viruses are going to be able to penetrate into testicles and eggs. The gene therapy might only affect the person given the treatment, not the DNA they pass on to their children.

And miss out on all the huge movie sales?

Science Fiction always outsell documentaries