Thursday, October 22, 2009

NINDS and Translational Research

For years now, many of us at the Parkinson’s Disease Foundation (PDF) and other Parkinson’s disease (PD) organizations have fretted that the brain research funded by the National Institutes of Health (NIH) has been too focused upon the basic processes of neuroscience and too little upon the next stage of research: finding clues to potential new therapies for specific conditions like Parkinson’s.

This next stage of scientific investigation is often called “translational research,” because it is here that the molecules and compounds identified as interesting in the laboratory are “translated” into animal studies to determine their therapeutic potential. Those compounds that make it through this phase may then go on to be tested in human trials, and from there – the hope is – to approved treatments.

So it was with delight that I learned at a recent NIH-sponsored meeting that from now on, university centers that are selected for five-year grants for Parkinson’s research under the prestigious Morris K. Udall program must show a commitment to translational research. The news was announced at a session arranged for representatives of PDF and other PD organizations by Story Landis, Ph.D., Director of the National Institute for Neurological Disorders and Stroke (NINDS), the entity that provides more than $20 million a year to support the 14 Udall centers in the program. She said that the Udall centers would henceforth be moving towards including a more translational focus to their work, and that those academic centers that cannot make the switch will need to seek sources of other support, such as the so-called program project grants that NIH offers.

Specifically, in the language of the request for applications recently issued by NIH, “Responsive applications will demonstrate proven ability or considerable potential to pursue rapid translation of research to clinical practice.” Applicants that are not able to demonstrate this translational component – however strong they may be on the basic science – will simply not be eligible for designation as Udall Centers.

Another encouraging note sounded at our meeting was by Robert Finkelstein, Ph.D., who directs the institute’s extramural grants program that includes the Udall Centers. He reminded us that the new focus on translational research reflects the development of the science of Parkinson’s. He observed that 15 years ago, NIH would not have had so much opportunity to focus on translational proposals because the underlying basic science was simply not there to support them. He also said that he welcomed this new direction because “we at the NINDS have the mission to cure Parkinson’s!”

The reformulation of the Udall Centers is not the only good sign of a stronger commitment to translational science at the NIH these days. Another is the appointment of two dynamic new research administrators to fill the new positions of Director of Translational Research (Bill Matthew, Ph.D. ) and Director of Clinical Research (Petra Kaufman, M.D., M.Sc.).

Dr. Matthew has a strong background in industry -- most recently, as leader of the Partnering and Business Development at UCB, an international biopharmaceutical company based in Brussels. His charge at NINDS will be heading up efforts to translate the results of laboratory research into treatments for neurological disorders.

Dr. Kaufman, who is considered to be among the nation’s leading experts in the design and management of clinical trials for neuromuscular disorders, has served for a decade as an associate professor of neurology at the Neurological Institute at Columbia University.

Another promising development with big implications for translational research at the NIH as a whole is the appointment of the new Director, Francis Collins, M.D., Ph.D.. In his first statement about his dreams for the NIH, he included as one of his five top priorities, “translating basic science into new treatments.”

The times are changing, and in some good directions. At PDF, we will be working with our colleague organizations to make sure that these good times continue to roll.

Friday, September 11, 2009

Parkinson's Disease: Principles for Health Care Reform

With President Obama’s dramatic address to Congress now behind us – and the public reaction, both supportive and critical, rolling in from all quarters – it is now clear that health care reform will be the main domestic policy issue throughout the fall (and perhaps beyond).

At my own organization, where our focus is the one million or so people who live with Parkinson’s and their families, we have received numerous expressions of concern and confusion from website visitors and constituents (and readers of our last blog post) about the meaning of various legislative proposals for health care reform, and their implications for the interests of the Parkinson’s community.

As a non-partisan organization, we support a balanced, bipartisan and comprehensive approach to the needs of the people we serve. We don’t know what the final form of the health care reform legislation will be, but we do think we know something about what should be in that legislation, whatever form it may take, if people with Parkinson’s are to be well served. We believe that these provisions, which we express on our website,, as a list of “Principles,” transcend the specific and often contentious issues of government plan vs. private insurance, or Republican vs. Democrat, and are in this respect “non-partisan” in the true meaning of the term.

We encourage you to take a look at, Parkinson's Disease: Principles for Health Care Reform.

We hope they will provide some common language for our community as they participate in the national conversation. And let’s hear your reflections and reactions!

Friday, August 7, 2009

What Does Health Care Reform Mean for People Who Live With Parkinson’s?

Careful observers of the Great American Debate About Health Care Reform — now taking place over proposed legislation H.R. 3200, or America’s Affordable Health Choices Act of 2009 — will have noticed an interesting change over the past week or so in the way the Obama Administration has chosen to frame the problem.

I first noticed it during a network newscast two weeks ago featuring David Axelrod, the President’s Senior Advisor. Mr. Axelrod had dropped the phrase “health care reform,” and replaced it with “health insurance reform.”

Why is this change in phrasing so significant? It is because the new phrase is an accurate description of what is actually being fought over in the debate, and the earlier one wasn’t.

Health care, by any reasonable definition of the phrase, refers not only to the way we pay for health care but the ways in which we organize it, deliver it and use it to encourage certain behaviors (especially those of a preventive nature) and avoid others. It is the Grand, Global Vision.

Health insurance, on the other hand, is just that: finding ways to pay for the care we need when we need it, so we all get covered and do not go broke using it. And for people who have lived for years with a chronic disease like Parkinson’s, the financial issues — crucial as they are — are not the only challenges they face. It is the Narrow, Necessary Vision.

Make no mistake, reforming health insurance is crucially important, both for the nearly 46 million Americans who have no health insurance of their own and for the economy as a whole that is groaning under the strain of a mega-industry that absorbs around 16 percent of our entire gross national product. But by itself, better health insurance is going to do little or nothing directly to improve the care that is received by the person with, say, Parkinson’s disease, who is enrolled in Medicare, Medicaid or a private insurance program … and whose care is often woefully deficient.

What are some of these deficiencies?

  • For starters, a person with Parkinson’s on Medicare visits the PD doctor about three times a year and spends perhaps 15 minutes with the doctor (the amount that is typically paid for by Medicare). Yet that person — along with his/her caregiver — typically needs time for the myriad of questions that come with a complex, lifelong condition like Parkinson’s. Many of these questions could probably be answered by a nurse practitioner or allied health professional, if one were available as part of a multi-disciplinary team, which — in the typical Medicare-funded ambulatory setting — is very rarely the case.

  • Then there’s the matter of home health care. Currently, Medicare pays only for such care that is required for only short stints of time during an “episode of care” – usually illness, injury and/or rehabilitation. The benefit is only temporary and available for those cases where further improvement is expected. Even though this kind of care is needed on a regular basis by many of those who live with advanced Parkinson’s — and costs a lot less than a hospital stay, which people with PD rarely need — it is simply not available to most people unless they are in a position to pay the very substantial costs out of their own pocket, which few can.

  • What about exercise programs, or physical and occupational therapy, or other support services that research shows can significantly enhance the quality of life for people with Parkinson’s? Like home health care, these programs are covered for only limited periods of time. These are hard to find now, and are not likely to be easier to access under any of the versions of health insurance reform that are currently being discussed.


The fact is that the current reimbursement models for health care are poor at using non-doctor personnel for jobs they are perfectly capable to handle; poor at supporting home-based care, even when it is demonstrably better for the patient and more economical for the system; and poor at addressing long-term quality of life support that is so much more important for people with long-term conditions like PD than it is for short-term conditions — even very serious ones. The current system is simply miserable at addressing the “chronic care needs" of Parkinson’s and other neurodegenerative diseases … and health insurance reform is unlikely to make this better any time soon.

So Mr. Axelrod is correct when he redefines the Obama goal from “care” to “insurance.” But it is too bad that he has to. Let’s hope that with successful health insurance reform, and a quickly recovered economy, we can soon turn our attention to a more fundamental and exciting challenge: getting better-designed health care to the people who need it.

Tuesday, June 23, 2009

Why do Promising PD Treatments Fail?

On Tuesday, June 9th, the second day of the Movement Disorder Society International Congress in Paris, Dr. Warren Olanow, one of the world’s leading Parkinson’s specialists, gave a brilliant and authoritative talk on the subject of “What’s New in Parkinson’s Trials?"

His focus was three high-profile clinical trials that have been watched intently and anxiously by people with Parkinson’s around the world.

  • One was the Ceregene trial, in which a growth factor called neurturin (CERE-120) was delivered via a gene therapy technique.
  • The second was STRIDE, in which a levodopa-COMT inhibitor (Stalevo(R)) was tested for its potential impact on improving dyskinesias.
  • The third was ADAGIO, designed to test the potential of rasagaline (Azilect(R)), a PD therapeutic that was approved several years ago to control symptoms of PD, for its potential to actually slow the course of the disease.

Dr. Olanow began his talk by saying that it has been an “extraordinary year …with many new trials involving drugs that offer promise to the patients we serve.” And he concluded it by saying it has been “wonderfully interesting.”

The trouble is, all three trials failed. What does this story mean for PWPs?

To this observer, it means several things:

  1. The obvious one is that the intuitive perspective of many clinical scientists is simply different from that of most people with Parkinson's. Studying something, however much one may yearn for it to be successful – as Dr. Olanow does -- is just not the same thing as living with it.
  2. Second, it means -- as the speaker himself pointed out in his closing minutes – that we need to do more work in the early stages of the investigative process (e.g., Phase-One trials) to provide greater assurance of efficacy before we proceed to put people living with Parkinson's through the strains and too-often dashed hopes of the much more expensive later stages (e.g., Phase-Three trials).
  3. Third, of course, it means, as Ira Shoulson, M.D., another major leader of clinical research and a collaborator with the PDF on several current projects, said to me recently, “clinical research is very, very hard!” Whether it be the imperfections of animal models of Parkinson’s disease, or the data-confounding impact of the notorious placebo effect, or the impact of physician-scientist bias (after all, they too want the trials to succeed!), or simply the immense complexity of defining “end points” – that, is what the measures should be of success or failure, and whether they will be accepted by the FDA – Parkinson’s trials are indeed very hard to do.

There is of course a silver lining to this cloud: that today’s failed trial may be the basis for tomorrow’s successful one.

In at least two of the three trials that Dr. Olanow mentioned, the data have suggested a next step that could have a different outcome. In the Ceregene trial, for example, when the managers went back to see how the trial participants looked three to six months after the trial concluded, they found that some had improved – suggesting that perhaps – just perhaps – the problem was that the trial concluded too early. And in ADAGIO, there does in fact seem to be some neuroprotective effect at lower doses of the drug (though, mystifyingly, not at higher doses), giving some grounds for hope.

In my next post, I will share with you some other things that struck me as interesting about the meeting – including a bird’s eye view of potential new treatments that are currently in the pipeline.