Rare mutation prompts race for cholesterol drug

NY Times via Columbus Dispatch (OH) ^ | July 14, 2013 | Gina Kolata

[neverdem]

She was a 32-year-old aerobics instructor from a Dallas suburb — healthy, college-educated, with two young children. Nothing out of the ordinary, except one thing.

Her cholesterol was astoundingly low. Her low-density lipoprotein, or LDL, the form that promotes heart disease, was 14, a level unheard-of in healthy adults, whose normal level is over 100.

The reason: a rare gene mutation she had inherited from both parents. Only one other person, a young, healthy Zimbabwean woman whose LDL cholesterol was 15, has ever been found with the same mutation.

The discovery of the mutation and of the two women with their dazzlingly low LDL levels has set off one of the greatest medical chases ever. It is a fevered race among three pharmaceutical companies, Amgen, Pfizer and Sanofi, to test and win approval for a drug that mimics the effects of the mutation, drives LDL levels to new lows and prevents heart attacks. All three companies have drugs in clinical trials and report that their results, so far, are exciting.

“This is our top priority,” said Dr. Andrew Plump, the head of translational medicine at Sanofi. “Nothing else we are doing has the same public-health impact.”

Dr. Gary H. Gibbons, the director of the National Heart, Lung, and Blood Institute, estimates that even if the drugs were expensive and injected, as many as 2 million Americans might be candidates. But if they could eventually be made affordable and in pill form — two very big...

--snip--

And there is another concern: cost. Each company’s drug is a biologic, a so-called monoclonal antibody made in living cells at an enormous expense, like some new cancer drugs that are already straining the medical system...

[Rodamala]

I wonder if down the road there might be a gene therapy treatment.

I wonder if one day they find out that western medicine is bunk, and that you are best off eating bacon sammiches on butter-soaked toast while drinking a fifth of whiskey and chain-smoking 2 packs of Lucky Stikes every day.

Hey are eggs "OK" this week?

Fools.

[exDemMom]

So, due to the recent supreme court case, who owns the patent on the mutation?

If the drug company creates a process for advancing this gene, will the people they gleaned the gene mutation from own the mutation or does the drug company? Or nobody?

The drugs being tested here are not genes and do not alter genes. They are monoclonal antibodies.

If I am to guess at their mechanism, I would say that they bind to the normal form of the enzyme that is defective in these women. Their gene defect causes a defect in an enzyme involved in the formation of LDL. The monoclonal antibodies attach to this same enzyme in normal people, deactivating it. They won't be able to make LDL without it. I think people receiving this treatment will need constant monitoring to ensure that their LDL levels remain within the normal range.

I think the recent Supreme Court case is going to put a halt into development of diagnostics based on genetic mutations. It costs too much to push medical devices through FDA approval to make it worthwhile to base a diagnostic kit on an unpatentable marker.

[exDemMom]

The unintended consequences should be interesting.

Indeed. Given the quirks of human physiology, I wonder what problems might show up in Phase 4 (post-approval) testing or even further down the road?

I also keep going around in circles about the causes of heart disease. Are cholesterol levels the drivers of heart disease, or are they a marker of it? Could another problem that hasn't been discovered yet be responsible for high cholesterol and heart disease?