Monday, May 17, 2010

Day 7: The Awesome C-Word!



Sunday 5/16 - Dream a little dream - life after a cure. To wrap up Diabetes Blog Week, let’s pretend a cure has been found. We are all given a tiny little pill to swallow and *poof* our pancreases are back in working order. No side effects. No more insulin replacement. No more diabetes. Tell us what your life is now like. Or take us through your first day celebrating life without the Big D. Blog about how you imagine you would feel if you no longer were a Person With Diabetes.

Like many of my readers, I've been hearing the "we're 5 to 10 years away from a cure" for what will be 34 years in July. I know a line of bull$#!t when I hear it. But I also keep close tabs on developments that even hint of the C-word (that word being "cure"). But I'm going to spin this topic a little first, because I actually DO believe there are a number of very promising developments that might actually cure type 1 diabetes in the not-too-distant future, and they're closer than many of you might think, although no one is testing them together yet, and if and when they are approved, it seems certain that someone will then start to test the idea of combination therapies.

In essence, the approach will be a kind of drug/treatment "cocktail", and it will likely require several different steps to actually finish the job, and it seems that its not likely to be a pill (at least initially), but a series of IV injections before we'll be able to kiss diabetes goodbye. But it is not at all inconceivable that one treatment may be able to fix the autoimmune response that destroys the insulin-producing beta cells, and that would essentially set the scaffolding for a cure, then another, second step would be needed to restore lost beta cell function to restore insulin independence.

Before continuing, I should introduce the doom & gloom scenario to get that out of the way. In November 2009, the fine (a term I use jokingly) doctors at the American Diabetes Association published a disturbing little "consensus statement" (see here to read it) co-authored by a dozen or so self-proclaimed "experts" on the subject of diabetes and a few other diseases were included for good measure. In essence, this group, which included former ADA President Dr. John B. Buse proclaimed that no form of diabetes will ever be cured; they said it's more appropriate to call it remission. To me, that's splitting hairs; call it whatever the f*%& you want to, if I don't have to deal with the day-to-day crap-o-l-a involved in managing blood glucose levels 24/7/365, even if it DOES require periodic refresher treatments, that's a cure in my book. Interestingly, the folks at the ADA who wrote this article did not seek a single iota of input from a single individual who actually HAS diabetes to see how they might define a cure, and frankly, I think this is one group whose contribution might be an important one to include the next time they decided to come up with a "consensus statement" about a cure, or lack thereof!

I should also note that the efforts for a type 1 cure may have relatively little impact on type 2 diabetes, which frankly is a tougher nut to crack because the etiology for that disease is poorly understood, and frankly, that's a much bigger cash-cow than type 1 is likely to be anyway. But even those patients may benefit from regenerative and/or islet replacement therapies, although solving the insulin resistance challenge remains unsolved.

With all of that aside, I'll give a quick scenario, followed by my ideas for life post-diabetes!

Imagine it's the year 2095, and your 5 year old child (who is now in kindergarden, and has been potty-trained for several years already) has started wetting the bed a lot lately, so you bring him in to see the doctor. The doctor takes a small blood sample with a fingerstick the office and delivers the diganosis a few minutes later: your son has type 1 diabetes, an autoimmune disease where the body's immune system screws up and destroys the vital pancreatic beta cells, rending him without the primary hormone needed to regulate blood glucose levels, and it is hyperglycemia leads to polyuria, thus the bed-wetting. He gives the child a SmartInsulin injection to reduce his super-high blood glucose levels right now which has been designed to last for about 4 weeks -- this should stop the bed-wetting tonight and make him feel better until he's all fixed up. The doctor tells you he can cure the disease, but it will require very careful adherance to a drug regimen or "cocktail" for 2 weeks, although the SmartInsulin injection should tide him over until he's cured. You sigh, willing to do what's necessary to restore your child's health, but you ask the doctor "isn't there an easier way?"

The doctor responds by saying this cure is an absolute cakewalk compared to what people with type 1 diabetes lived with back as recently as 2010, and absolutely mindblowing compared to what people in the 1920's had to endure. Back then, type 1 diabetes was a burdensome, ridiculously-complex, costly and never-ending treatment regimen that helped to stave off long-term complications but still failed to provide perfect blood sugar control, and the demanding treatment protocol frequently caused clinical depression in countless patients.

In hindsight, he admits, "it was almost inhumane treatment, but it was better than death." All you'll need to do is take a few pills on schedule for 2 weeks, the pills taken during the first week will re-educate the immune system, then the pills taken in the second week will regenerate new beta cells to restore the cells that were destroyed. He comments "Imagine a lifetime of bloodtests, injections or wearing a huge insulin pump (the size of today's pagers) that has to be refilled every few days, costly supplies before there was universal healthcare coverage for all, regular doctors visits, routine glycemic variation including dangerous episodes of hypoglycemia (often without symptoms that some believe was due to imperfect folding of the biosynthetic proteins made by bacteria and yeast in those days), high blood sugars that drained you of energy and caused dry mouth syndrome ... the list of daily burdens on the patient and long-term adverse events was almost endless!" He adds that once curative therapies emerged, there were many tests that needed to be done to determine which autoimmunity treatment and regenerative therapy worked best for which patients, so there was often trial-and-error going on -- today, the treatments address all bases. Now, however, a combinantion therapy works to cure almost everyone.

You respond, "I guess this IS much better than life in the dark ages of diabetes care, but it's still a nuisance, and those pills are so big for a 5 year-old!"

About 3 weeks later, after following the drug cocktail, you bring your son in for a final checkup, telling the doctor that there has been no incidence of bedwetting since your initial visit. Another fingerstick test provides a C-Peptide count and an fructosamine test run in the office reveals that glycemic control has been perfect since the last visit. The cure has been successful, and the doctor comments "I hope the cure wasn't too much of a burden -- researchers are working on a single pill that can do everything, but it's still in pre-clinical trials right now."

With that, your child is cured of what was once a lifetime of expensive and burdensome, and sometimes ineffective treatment, and a death sentence prior to 1921. What's more, this low-cost treatment is now so easy that it's available even in remote parts of the world because it's so cheap (as a generic drug) and it's also easy to deliver, and type 1 diabetes at least has been relegated to the medical history books.

Sci-Fi or Reality TV?

Is this sci-fi, or could this someday be reality? Well, there are a number of elements that suggest we are moving in that direction, although there are a number of hurdles that must be addressed first.

First, the hardest element to address seems to be the autoimmune response that causes type 1 diabetes in the first place. But at present, there are 2 drugs entering Phase III human clinical trials that might arrest the autoimmune response. There are at least 3 that I am aware of, and all are in late-stage (meaning Phase III clinical trials). Lilly and Macrogenics have one called Teplizumab (which is good for Lilly, as it's share of the insulin market continues to slide, since they offer only Humalog which makes the company a one-trick pony in the insulin biz). And GlaxoSmithKline also has a very similar product called Otelixizumab in the pipleline, along with development partner Tolerx, whose CEO writes a blog the entitled "The Green Chair" that you can read here which may be only slightly further ahead in development. You can be damn sure both greedy big-pharma partners will push, push and push more to make these treatments applicable for almost anyone with type 1, using the same method they've used to introduce costly new drugs using stacked studies, many of which aren't even blinded. And there's little doubt they'll charge handsomely for the product, we're probably talking like $15,000 for it. The downside of these anti-CD3 treatments seems to be recurrent mononucleosis in some patients (its not understood exactly why yet), but even that seems a small price to pay all things considered, as the daily risks of insulin treatment alone are almost as severe. We may also see the Swedish company Diamyd come into play here (see my interview with them here), and their treatment may ultimately prove superior to anti-CD3 treatments, although only time will tell for sure.

To solve the second half of the type 1 diabetes problem, there are several different approaches in development. One is islet transplantation, and there are several companies pursuing that, including New Zealand/Australia-based LCT (Living Cells Technology). Others including Geron Corp. as well as the company that the recently-stepped down CEO of the JDRF, Alan Lewis, ran which is now known as ViaCyte, are pursuing stem-cell therapies to regenerate islets that can be transplanted into patients whose islet cell autoimmunity has been eradicated. The idea there is that they can generate islets using our own DNA and create the beta cells in a lab and assuming the autoimmune response is gone, there will be no other immune reaction.

Then there are the regeneration companies, among them Exsulin, which counts Dr. Alexander Fleming, who formerly ran (for 12 years) the U.S. FDA's Metabolic Group (which included ALL diabetes treatments) as a leader, so this guy can navigate the FDA perhaps better than anyone else on earth. And the Toronto company JDRF seed funded known as Transition Therapeutics has another regenerative therapy in development. David Mendosa in 2008 wrote that it looks like Exsulin's approach could cost about $20,000 (the best I can tell), although with changes in the insurance business looming, it's not as if one company will incur anything different than the others, plus the cost will still likely be less for them to pony up for this than to continue paying for ongoing care for people with type 1 diabetes. And it seems most likely that the cost for all of this will come down significantly, though, so by 2095, the cost for both treatments will be pretty cheap. And refinements will make the side effects by then to be pretty minimal, as the companies try to one-up one another with better and better products.

I'm not naïve; not all of these options will make it to commercialization, and its quite possible that even if one or more DOES make it, one treatment may not work in all people with type 1 diabetes, or may be more effective in some people but not in others. But that's waaaaaay closer than we are right now! We may ultimately find that certain cure approaches (e.g. transplantation vs. regeneration) work better in different groups of people, but in another eighty-five years, that should all be sorted out!

So what about the kick-@$$ party?

We've heard about beach parties catered by Crumbs and oompa loompas, the latter of which gave me the idea that realistically, a celebratory trip Hershey Park might be a realistic place to hold a kick-@$$ celebration party, and the Diabetes Online Community is all invited. Instead of being tempted (or taunted) with chocolate and not being able to enjoy it, we can actually enjoy it this time without too much thought! But the first thing I'm doing is enjoying a pizza, and I won't have to worry about extended boluses or morning hyperglycemia. Although I don't expect any pharmaceutical company to pitch in a dime for this, as we we're their cash cows, and now that little party is over, but I agree that we'll all have a boatload of money that we'll be free to enjoy after this crap is over. And having a bonfire of meters, pump supplies, insulin pens, and all the other crap also seems in order (I wonder if Hershey will let us do that onsite?). But the thing I'm most looking forward to getting rid of is the test strips and meters, which companies ranging from Abbott, J&J and Bayer and the rest who have been milking this forever will take take a pleasant financial hit on. Too f'ing bad, IMHO. They're sure to find something else to bilk for billion$ before too long, we can be sure. But if a few go under in the process, we can laugh about it!

But at the risk of sounding too pleasing, we can't just eat to our hearts content for long, lest our waistlines pay the price. But the initial party will be worth it! We probably will have periodic reunions before we have some other health ailments to worry about, but realistically, I honestly believe that new treatments that address the disease itself, rather than continued palliative treatments to address the SYMPTOMS of diabetes, might not be too far away. And I like to think the party will be awesome, and life post-D will take some getting used to, but if anyone can handle it, it's the people with diabetes. Realistically, the commeditization for these treatments seem very appropriate. And I hope an occasional reunion might be in order once this party is over!

11 comments:

Bennet said...

Great Job Scott. That there is one kick@$$ post.

Funny and informative. I particularly appreciate your gift for reading all the industry trial double speak press releases and translate it into the language of actual humans.

Lois Lane said...

Awesome job and incredible post! I look forward to a cure. Of course, I wont see it but to know that future generations wont have to suffer with the day to day makes me smile.

I agree with Bennett "that there is one kick@ss post."

Jim said...

This was very well thought out and written, you may even be able to turn around my optimistic pessimism and make me more of an optimistic pessimist. But during the kick@$$ party, instead of a bonfire, can we recycle all the old meters and stuff?

Jenny said...

Let's hope that day comes fast!

Since something like 2/3rds of all middle aged people adults are insulin resistant, but only about 9% develop Type 2 diabetes, beta cell rejuvenation/replacement would make a huge difference for Type 2s also. You don't get the very high blood sugars characteristic of Type 2 without a lot of dead beta cells. Most have lost from one half to 80% of their beta cells at diagnosis and the rest are destroyed by a decade of exposure to the very high blood sugars (fasting bg around 180) that most family doctors consider acceptable for Type 2s.

Unfortunately, insurers are not likely to spring for islet treatments for Type 2s since they prefer to blame them for their condition and let them get those fatal heart attacks that keep costs down. They currently don't pay for diabetes education and in many cases discourage insulin and tight control.

Scott said...

Thanks for the comments everyone! Jenny, you're certainly right about all elements, although I should note that the Transition Therapeutics regeneration effort, which was seed-funded by JDRF, has decided to pursue type 2 trials FIRST, and will then extend them to type 1. The reason is obvious, it's a much bigger target market. However, I do think progress is being made towards understanding the root cause of type 2 as well, but whether the cost will be covered for regeneration efforts is more of a public policy issue and its unclear whether insurance reforms will address that (if I had to guess, I'd say probably not), so only time will tell. I do think that if the costs of regenerative therapies come down it can be offered to a much larger universe not only in the US, but on a worldwide basis.

type1emt said...

Great post.(it's interesting to read how it all actually is likely to play out,vs how we'd like it to)

Michael Hoskins said...

As always, thanks for your informative and knowledgeable posts, Scott. This was a great one, too! Love the bonfire idea - I'll definitely join in!

Bennet said...

Jim

I think the meters need some actual violence from time to time. Oh we didn't wait for the cure, we just kicked some meter @$$ for mental health.

See: http://www.ydmv.net/2008/08/smash-your-meter-on-youtube.html

Cara said...

A) Hershey ROCKS!!!!
B) I said pizza too! :P

k2 said...

OUTSTANDING post on every level Scott!

Kathy said...

Well said. I believe that we are very close to the cure. I think that a blending of all of these fronts will lead us there. The pig islets will allow more transplants and enhance that knowledge. Regeneration, I'm afraid might only help those with some beta cells left, but should do the trick. Stem cell therapy, once we get that rolling in this country, might trump all of these. But the point is that we are very close in all of these directions. Someone will get there. Its really not a perpetual race.