Kalydeco is this little Idol I bow to every morning. I am holding back on the trial because my mutation is heterozygous S1235R and I am sixty three years old. That irreversible damage has pretty well done its best and frankly I would rather see somebody else on the drug.
Ever since CF’s biochemistry and genetics has been known, we have been trying to throw good genes at our mucosal cells. At first, the genes were placed in a super solvent like DMSO and breathed as a mist. Soon scientists had shot benign viruses full of good genes and infected patients with good genes by breathing a mist of the viral concoction. This was and is successful to some degree but very short term and requiring isolation because of the unknown dangers of an engineered virus. The danger was believed to be nonexistent but it would be irresponsible to expose the general population to a controlled trial of this nature.
Not so with Kalydeco, but the understatement of the century was Forbes praise for Kalydeco as “The Drug of 2012”. Uh, somebody just homebrewed the equivalent of the atom bomb and it gets relegated to drug of the year? Is it dangerous and are there a thousand unknowns? Yes and no, and that is what you get with a fast tracked drug. It is a no brainer, a drug that might eventually have a fatal side effect verses a disease that most certainly is life shortening, will be advanced ahead of the most extreme cautions all drugs eventually go through.
Scientists enjoy reading history like most people but we ferret out books on the history of antibiotic discoveries, new advances and of course medical tragedies. I was in France about fifteen years after a new tranquilizer was prescribed to pregnant women and quickly pulled from the market when births showed the horror of the drug’s side effects. “Thalidomide Babies” became a term in our language as these new bundles of joy were born with no arms or legs, missing segments of limbs like a hand at the shoulder with no arm in between or hands and feet seemingly exchanged. Most were normal intelligence and for the few years the media followed them we saw many profiles in courage as children missing arms would learn to use their legs and feet as arms and hands or such. Europe always has had a more moderate track for drug approval but the whole world tightened their drug vetting regulations after Thalidomide. I saw hundreds of these teens (grown Thalidomide babies) lining popular sites in Paris, begging for change.
Welcome to a brave new world! It isn’t impossible that another” Thalidomide” will escape into the general population, but drug testing has history to help with the extensive and exhaustive testing done before it ever is given to people. Kalydeco has gone though 99% of its testing and controlled trials are now years old. It is as safe as it can be, the variety in human makeup is always the last unknown. You won’t know how it will affect you until you take it. This is true of all drugs and many foods.
This isn’t a simple drug. Several things are required for a genetic drug to do its job. It needs something that will attract the drug to its target gene, this is called a vector. Sort of like FedEx coming to a business that always has deliveries and shipments, the drug comes to the loading dock. It next needs to deliver a service engineer for a quick parts swap. At genetic address 551 in the CFTR gene there are some claim jumpers that should be evicted called aspartic acid. Aspartic acid is similar to the genetic ladder rung guanine. Aspartic acid fits the same bond pattern as guanine but it doesn’t template or send the correct instructions. It’s like a bad cell phone connection and you miss some critical information. Kalydeco is a designed drug which can’t really be said for most of the medicine out there.
All fantastic drugs like the first small pox inoculations get a little nervous humor poked at it. Indeed aspirin kills a first time patient possibly one every day because of human variety. That means any drug could be fatal to somebody and it comes down to risk over benefit. You won’t be given Kalydeco and ignored. Your doctors will be monitoring things from the first dose.
I wonder what toxins might be released as infection and inflammation begins to flood the liver and kidneys due to Kalydeco improving a person’s health. A prime target of Kalydeco ends up releasing pretty much all aspartic acid for guanine and that error is in every cell in your body. If just the mucosal membrane cells were stripped of their aspartic acid, possibly this repair process is skewing ALT numbers. An aspartic acid quantity not normally expected by the liver may be showing good news. Maybe too much good news and hence doctors are adjusting the dosage to allow the liver to process the excess goo. The liver is sort of the ultimate chemical laboratory and if there is genetic variety we don’t know or understand, a lot may be hiding in the liver. Doctors are sketchy when test numbers are being discussed. Try to get a straight answer to how high ALT’s and other liver function tests must be for liver failure, most will evade a definite number except to say you are a long ways away. At 250, it is a concern for sure, but what if your number is 500 or 5000? Or, are you dead long before 5000 ever shows up? You are probably in need of a liver transplant when you start creeping into the thousands, but my brother’s numbers are high (1100) from Hepatitis and Agent Orange, both from the same S.E. Asian war. He is 68 and very healthy.
If you have the mutations to be made better with Kalydeco, go for it. Mutation G551D gets the full body massage, but as a CF moderator for other mutations if you could arrest further damage. Insurance is in it for the long term, generally ninety years opposed to ninety days like most businesses. Kalydeco is going to known as the genetic gateway drug if my prediction holds. The high price of drugs over the last twenty five years has been to pay for genetic drug research and a lot of retooling. Insurance is paying these seemingly outrageous prices because they know when to back a good horse and this is a huge promise, like Secretariat born again. It is a horse that won’t lose.
Hundreds of enzymes are made in the liver but none are the type that digests food in the conventional sense. Higher than normal liver enzyme leves often include digestive enzymes but those are mostly supplied by the pancreas attached to your liver through a common bile duct. Bile works like an enzyme/solvent for lipid and large fat molecules but is in fact a waste product of the liver that we repurpose in digestion of fats. You don't want high liver enzyme numbers, this usually implies a damaged liver, with inadequate capacity or one that is being overloaded by toxins.
LL
Although it can't reverse the amount of damage in my remaining lung (left lobe lobectomy in 2010) it will prevent me from further damage. I figured at 53 even if it didn't work for me, I would be helping all the newborns and young children out there by participating in this trial. At this point I think that it will help me live even longer and hopefully everyone will benefit from this drug some day soon.