How To Spend All That Ice-Bucket Money? Multiple ALS Research Leads Heat Up

In this image from video posted on Facebook, courtesy of the George W. Bush Presidential Center, former President George W. Bush participates in the ice bucket challenge with the help of his wife, Laura Bush, in Kennebunkport, Maine. (AP)

In this image from video posted on Facebook, courtesy of the George W. Bush Presidential Center, former President George W. Bush participates in the ice bucket challenge with the help of his wife, Laura Bush, in Kennebunkport, Maine. (AP)

I sighed this week when I heard, “Hey, Mom, do we have a clean bucket and some ice?”

Yes, the viral ALS ice-bucket challenge that has swept the country had reached our household as well. And though my daughter averred that she would never have heard about ALS otherwise, it pushed some of my cynic buttons. (My favorite response so far had come from an acidly hilarious Facebook friend who advised celebrities: “Just write a check to support ALS research. If you still need a gimmick and social media attention, set your hair on fire instead.”)

For me, the trouble was that I had looked into ALS research a few years ago and it had struck me then as extraordinarily frustrating. It was the field that first taught me that it’s all too common for a potential treatment to look good in initial testing and then fail to pan out when tried in a bigger clinical trial. That happened with ALS over and over again. And meanwhile, patients faced inexorable neurological degeneration and far too early deaths. (One of my most admired colleagues, Dudley Clendinen, died of ALS in 2012 after eloquently chronicling his time with it.)

But then I thought: Let’s be positive. Whatever the narcissistic elements of the ice-bucket dousings, the challenge is raising millions of dollars — more than $50 million as of Friday, from more than a million new donors, according to the ALS Association. And maybe ALS research has changed?

Indeed it has, say scientists working in the field. Not that it looks like there’s a cure around the corner, but there has been major progress of late, they say, and we can expect more to come.

“In about the last seven years, the genetics of ALS has just exploded the field, and just come up with so many new ideas for how we can tackle the disease,” said Avi Rodal, an ALS researcher at Brandeis University whose work is funded by the Blazeman Foundation for ALS.

Dr. Lucie Bruijn, chief scientist of the ALS Association that is reaping the ice-bucket windfall, also describes a field that is forging ahead in multiple directions. “The understanding of the disease, the research that has gone into it, has grown exponentially,” she says. “So we’re much closer to understanding the complexity of the disease and how to approach it in a very different way from before, when many of the trials were challenging partly because we didn’t understand the disease as closely.”

The Association, she says, is focusing on six main areas, and the ice-bucket money will likely be divided among them: “We want to invest in many areas,” she says, “to be sure not to dilute it too much but to be very strategic that we don’t put all our eggs in one basket.”

Those areas, in brief and lightly edited, as she described them:

1. Genetics:
About five to 10 percent of ALS runs through families, but 90 percent is sporadic. However, we’ve found that many of the genes we identify in familial disease are potential risk factors, and certainly also seem to be involved in the sporadic form. So there’s an underlying genetics in all ALS, but sometimes it’s more dominant than others. Continue reading

Don’t Miss: The ‘Forced Intimacy’ Of ALS Illness And Paralysis

Charles Dharapak/AP

Charles Dharapak/AP

Holly Ladd may be losing her voice to ALS but she can still write with breathtaking beauty and depth. Don’t miss her Cognoscenti post, Forced Intimacy: When Illness Makes Us Let Down Our Guards. An excerpt:

By necessity, there are a whole lot more people in my life now. Most notable are the four women who come at different times and frequencies to care for my daily physical needs. These people bathe me, brush my teeth, wipe me, feed me, get me in and out of bed, and dress and undress me. As each week passes, they bore through the rock-hard walls of my self-consciousness, shyness, embarrassment and grief to move in close enough to keep me clean and safe — and I fight them at every turn, mistaking pride for dignity.

Some of those who care for me have such a well-worn familiarity with this disease that they anticipate both my physical and spiritual needs before I can imagine going there. They prepare me, and they prepare the path in front of me.

There are medical providers who know the science and my body — how it is collapsing. Two or three have also seen some of how my heart has broken. And my psychologist helps sort out the feelings I have about impending death from those that were born in ancient losses. With a couple of these, I discuss both heart and health, and they will be trusted with making the final call.

The full post is here. I encourage you to leave a comment to Holly there, and her Tumblr blog is here.

$25K Prize For Predicting How Fatal Disease Will Progress

ALS is also known as Lou Gehrig’s disease, for the famous baseball player who died of it (Wikimedia Commons)

Calling all computational minds. You don’t need to cure ALS. You just need to predict its progress better than we can now. Your reward: A $25,000 prize from the Cambridge-based nonprofit Prize4Life — and the knowledge that your work could hasten the development of drugs for the fatal neurological disease.

Why offer a prize just for predicting the course of a disease rather than curing it?

Melanie Leitner, Chief Scientific Officer of Prize4Life:

“Our focus is on attacking ALS from all angles, including prizes for innovations in both disease prediction and therapeutic breakthroughs. We recently launched the ALS Treatment Prize for a therapy that does just that: slow down disease progression disease. We’ve created this prize because finding an algorithm to predict progression will be enormously helpful for future clinical trials and will help speed up the discovery and development of the drugs that will help ALS patients in the future (hopefully including some of those that were incentivized by the ALS Treatment Prize!).”

And didn’t someone just win a big ALS prize? How is this one different? (Here’s the New York Times story from last year: $1 Million Prize to Inventor of a Tracker for ALS.)

Melanie Leitner: Continue reading

Dudley Clendinen Signing Off As ALS Takes His Voice

Dudley Clendinen and his daughter Whitney in 2007

What can you do but cry and laugh a bit and bow your head in homage to a spirit so big and bright that it turns nerve degeneration and fast-encroaching death into a literary and radio event worth celebrating?

This morning was Dudley Clendenin’s final broadcast. Dudley is an author, former reporter and editorial writer for The New York Times, and an all-around dashing and widely beloved southern gentleman. Since late 2010, he has also been a patient diagnosed with ALS, or Lou Gehrig’s Disease, which leads to progressive weakness, paralysis and death.

But instead of curling up and despairing, Dudley has spoken out, writing an acclaimed op-ed piece and sharing his thoughts and experiences on Baltimore’s WYPR show “Maryland Morning” in an extraordinary series called “Living with Lou: Dudley Clendinen on a Good Short Life.

It is brave radio, because Dudley’s voice was sure to deteriorate as the disease progressed, and indeed, he is very hard to understand now. (WYPR provides transcripts of the last two shows.)

But it is riveting radio, as well: Even as my eyes filled with tears, I found myself on the edge of my seat, eager to hear what this lyrical and loving man would teach me as he faced that place where we all must go. I laughed when he said he’d like to borrow his epitaph from the title of an Ogden Nash collection, “I wouldn’t have missed it.”

But the tears overflowed when he said, in his near-incomprehensible rumble, that he felt grateful because “Everyone has to die but not many of us are asked to talk about it.” Continue reading

Dudley Clendinen On ALS: When It’s Time To ‘Buy A Pistol’

Dudley Clendinen and his daughter Whitney in 2007

Warning: Do not read Dudley Clendinen’s essay about planning his own death unless you’re in a place where you can leak tears.

Dudley has outdone himself, and that is saying a lot. We’ve linked before, here and here, to his heartbreaking, heroic radio broadcasts for WYPR about his ALS, or Lou Gehrig’s Disease.

Now Dudley, a former New York Times reporter in Boston and editorial writer, has switched back to print, in this New York Times essay titled “The Good Short Life.”

Dudley had spoken in his broadcasts about grappling with his diagnosis and the steep decline it means for him. He talked about “doing the math” of his life, figuring out what he wanted to “add to the pile.” About trying to “defang” his dying for his loved ones by writing them long, entertaining letters. And about the odd liberation that comes when you know you’re dying and don’t have to worry anymore about what you eat or wear. With his extraordinary gift for storytelling, Dudley is effectively giving us “death lessons,” letting us watch him go out with style. He talks about seeking the “responsible, grown-up, good-humored” way to prepare for death.

Now, in the Times, he translates that quest into a concrete plan: He doesn’t plan to ride his A.L.S. all the way down into total paralysis. A friend comments that “We need to go buy you a pistol, don’t we?” And he replies with a smile, “Yes, Sweet Thing. We do.” He writes:

There is no meaningful treatment. No cure. There is one medication, Rilutek, which might make a few months’ difference. It retails for about $14,000 a year. That doesn’t seem worthwhile to me. If I let this run the whole course, with all the human, medical, technological and loving support I will start to need just months from now, it will leave me, in 5 or 8 or 12 or more years, a conscious but motionless, mute, withered, incontinent mummy of my former self. Maintained by feeding and waste tubes, breathing and suctioning machines.

No, thank you. I hate being a drag. I don’t think I’ll stick around for the back half of Lou.

I think it’s important to say that. We obsess in this country about how to eat and dress and drink, about finding a job and a mate. About having sex and children. About how to live. But we don’t talk about how to die. We act as if facing death weren’t one of life’s greatest, most absorbing thrills and challenges. Believe me, it is. This is not dull. But we have to be able to see doctors and machines, medical and insurance systems, family and friends and religions as informative — not governing — in order to be free.

I’ve never seen anyone face death with such joie-de-vivre. When he makes me cry, I can’t tell whether it’s because it’s all so damned sad or so damned beautiful. I only know that when my time comes, I’m going to try to channel Dudley.

A policy moment: His piece raises a ticklish question about paying the monumental costs of end-of-life care. He writes:

Lingering would be a colossal waste of love and money. Continue reading

Patient-Driven Social Network Refutes Study, Publishes Its Own Results

It’s probably the first crowd-sourced clinical trial ever, and it certainly marks a breakthrough for social media as a force in the realm of medical research.

The health-data-sharing website PatientsLikeMe published what it is calling a “patient-initiated observational study” refuting a 2008 report that found the drug lithium carbonate could slow the progression of the neurodegenerative disease amyotrophic lateral sclerosis or ALS. The new findings were published earlier this week in the journal Nature Biotechnology.

The original claims about the benefits of lithium carbonate were presented in Italian at a medical conference in 2008. One member of PatientsLikeMe found the conference poster and translated it. Later that year, the findings were published in the Proceedings of the National Academy of Sciences.

More and more ALS patients began asking their doctors for off-label lithium and talking to each other online about their experiences. Ultimately, 348 ALS patient members reported their off-label use of the drug on PatientsLikeMe. At an International ALS/MND Symposium, PatientsLikeMe, which is based in Cambridge, presented preliminary results that lithium was not having an observable effect on the disease progression of these patients. The results were revealed before any of the formal follow up trials enrolled patients.

To further capture the data using a clinical trial model, PatientsLikeMe says it “developed a novel algorithm designed to match patients who reported taking lithium with a number of other ALS patients that had similar disease courses. By using a matched control group, PatientsLikeMe was able to reduce biases associated with evaluating the effects of treatments in open label, real world situations and improve the statistical power of the study making each patients contribution more meaningful.” The study included 149 patients on lithium, compared to 447 not taking the drug, says Paul Wicks, Phd., one of the study’s lead authors and the group’s director of research and development.

Obviously, this type of trial can’t match the potency of a double-blind, controlled clinical study, the gold standard. But, Wicks says, this type of patient-centric study has a different kind of power, and it also has speed in its favor. “This is a community movement,” Wicks says. “The patients taking lithium were self-choosing, they were getting it from their own neurologist.” Moreover, he says: “Tapping into the power of a patient community can really speed up trials, it’s a disruption of the status quo and there’s no reason this couldn’t apply to diabetes, asthma, depression, and all the other diseases we now cover.”

Another plus, he says, is the transparency of the information: “Along with the manuscript, Wicks says, “we’ve uploaded all of the data, so any other ALS researcher can download the information and double check our math.”

‘Life Gets So Quirky And Interesting When You’re Dying’

Dudley Clendinen and his daughter Whitney in 2007

I wrote last month here about the notable WYPR radio series featuring Dudley Clendinen, author and longtime writer — and former Boston bureau chief — for The New York Times. Now the latest installment is out here, and continues to amaze me. Dudley talks, in a voice now slurred but still deep and rich, about writing people long, entertaining letters informing them of his incurable illness — ALS, or Lou Gehrig’s disease, which he has nicknamed “Lou.” In this latest 12-minute installment, he discusses trying to make his terminal diagnosis easier for his loved ones.

It’s not just that Dudley remains the consummate wordsmith he always was. To me, it’s that, in his compulsion to share his thoughts and feelings so eloquently, he’s becoming a model for how to face death. Why were “Tuesdays With Morrie” or ” The Last Lecture” such huge bestsellers? My guess is that it’s not just because they shared life lessons from people nearing the end. It’s that we’re all headed there eventually, and we desperately need death lessons on how it’s done. Here are a few of Dudley’s latest:

“Most of us aren’t good with doom. And when we have a friend who’s doomed, it casts a pall on the meetings. And I thought, ‘Well, I don’t want my friends having to walk across the street — metaphorically — every time they see me coming, because this is just another thing. We all have something.'”

So he’s written nearly 100 letters to people.

I think it’s a big dump — to unload on someone, in a single conversation when they’re not expecting it, that you have a disease that’s going to kill you in a very ugly way in two or three years, and half that time may not be pretty. That’s really not fair to do to someone. Because the disease is, after all, not about me; it’s about my friends, it’s about my family, it’s about my daughter. In other words, it’s not my event primarily, because I’m here and then I’ll be gone, but my passing is going to stay with the people who love me — they’re going to grieve about it from the time they hear of the disease until I die…It’s kind of like a wedding or a funeral: You know it doesn’t belong to the people who are in the service.”

So I’ve been writing long, kind of entertaining — I hope — letters…to try to defang it and make people realize that I’m comfortable, so they don’t have to be uncomfortable. I want to defang it. And when I talk about it, I risk being a bore because I want them to know it’s just conversation. And it’s pretty damned interesting because life gets so quirky and interesting when you’re dying. I’m the lucky one. I get to eat what I want, I get to see who I want, I get to go where I want, I get to pay the bills I want and not pay the bills I don’t want, I get to wear the clothes I want, and no one can say, ‘Why are you being so odd today?’ This can be fun for me. It’s not so fun for you.

[To quote the great Janis Joplin] ‘Freedom’s just another word for nothing left to lose.’ When you have Lou, that’s kind of the way you are.

Heartbreaking, Heroic Radio: Dudley Clendinen On Having ALS

Dudley Clendinen and his daughter Whitney in 2007

I can’t wait to hear more heroic radio from Dudley Clendinen, but how I wish he didn’t have his amazing material.
Listen to him here on the Baltimore NPR station, WYPR.

How to describe Dudley? He’s a former Boston bureau chief and editorial writer for The New York Times. He’s authored wonderful books and is, in general, a model writer, lyrical and compelling. He’s a southern gentleman. The couple of times that I’ve met him, the word that came to mind was “dashing.”

And now, he’s a patient with a terminal diagnosis of ALS, or Lou Gehrig’s Disease, and, true to form, he’s going to go out storytelling. His first episode of a series called “Living With Lou” aired today. Already, his voice is altered, his words slurred. But the inimitable grace remains. Today, he describes his symptoms, the growing suspicion that he had the disease, and then his diagnosis and how he processed it.

By the morning after receiving the diagnosis, he says, he decided to see it as a test of really living responsibly. “The question is, what’s the loving thing to do, for yourself, and the people who care about you and love you? That’s really a way of saying: What’s the responsible, grown-up, good-humored thing to do?”

He was “doing the math” of his life, he said, and decided that “I have some other things that I want to add to the pile.” Stay tuned.

NYT: Boston Doctor Wins $1M Prize For ALS Tool

The most famous person with ALS, physicist Stephen Hawking

What do you do when you’re determined to find a cure for a horrible disease, and science is moving just too slowly for you? One option is to create a “large inducement prize” to spur research, as Prize4Life did for the degenerative disease ALS, better known as Lou Gehrig’s Disease.

In a fascinating New York Times exclusive today, writer Bina Venkataraman reports that a Beth Israel Deaconess Medical Center doctor has just won Prize4Life’s $1 million ALS prize for inventing a powerful new tool to help track the muscular degeneration caused by the disease. It’s not a cure, but it could help researchers screen potentially lifesaving drugs much faster.

BOSTON — Tracking the inexorable advance of amyotrophic lateral sclerosis, the deadly neuromuscular ailment better known as Lou Gehrig’s disease or A.L.S., has long been an inexact science — a matter of monitoring weakness and fatigue, making crude measurements of the strength of various muscles.

This imprecision has hindered the search for drugs that could slow or block the disease’s progress. But now a neurologist at Beth Israel Deaconess Medical Center here has won a $1 million prize — reportedly the largest ever for meeting a specific challenge in medical research — for developing a reliable way to quantify the small muscular changes that signal progressive deterioration.

The winner, Dr. Seward Rutkove, showed that his method could cut in half the cost of clinical trials to screen potential drugs for the disease, said Melanie Leitner, chief scientific officer of Prize4Life, the nonprofit group that created the competition. Continue reading