Notes from a Day Spent Listening to Scientists Judging PDF Research Applications

Last Friday, March 16, was the occasion for reviewing applications for PDF’s International Research Grants program and Research Fellowships programs. Before us were some 30 proposals from some of the best young (and not-so-young) scientific investigators in the world.

As I sat there in the meeting as an observer, listening to the members of our scientific review committee as they made their comments and pronounced their judgments, I found myself scribbling notes on what seemed to be the principles on which they were basing their decisions. What they were saying, it seemed to me, said a lot about how we go about choosing the projects we will fund. Here are some of the ideas I picked up:

Relevance to Parkinson’s Disease. Every proposal that we fund – without exception -- must show promise in its potential to advance our understanding of PD, or charting the path to its cure.

New Ideas, New Investigators. To maximize the leverage of the program, successful applications will be one of two kinds. One is the innovative pilot project that shows promise for leading to a larger-scale endeavor that will be eligible for funding from the NIH (drawing on PDF’s “leverage” function). The other is the Parkinson’s-related application from an exemplary scientist whose past contributions have been largely in areas other than Parkinson’s – and who could be inspired by means of the PDF grant to turn his or her attention to PD.

Demonstrating Results. The renewal of an earlier award to the same scientist depends on the investigator’s ability to show “significant progress” since the first grant – that is, you don’t get a second grant if you can’t show that you used the first grant well.

Establishing Credibility. To make it through the grant review process, good ideas aren’t enough; the applicant needs to be able to demonstrate – both in his/her personal accomplishments and in the reputation of the lab in which the work will be done – a stellar track record in producing innovative and useful science.

Including Advocates in the Research Process. The meeting included three members of Parkinson’s Advocates in Research (PAIR), a PDF program in which lay leaders in the PD community are prepared to take on a variety of roles advocating for clinical research. An example of their contribution came early in the day, when one of these advocates raised a question about the validity of animal models in Parkinson’s research, which generated a spirited exchange among the scientist members of the committee.

I hope you are as impressed as I am with this little vignette of PDF’s research culture!

I conclude with a quotation from a memo on the mission of the program from Dr. James Beck, who is our Director of Research Programs at PDF and staffs the grants review committee. In thanking the scientists in the room, he said, in effect: “The two groups that will benefit most from your decisions today are not even here. One is the world of talented young scientists whose work will be made possible through your efforts. The other is the community of almost one million in the U.S. who live with Parkinson’s. In behalf of these two communities, PDF thanks you!”

Amen, James.

WPC Roving Reporters: Day Two Science

The 2nd World Parkinson Congress continues its three days of sessions discussing the latest news in Parkinson’s science and care. PDF’s reporters have been listening in to a variety of these sessions. They are reporting back what they have seen and heard….and sharing the most important messages they are hearing as people living with Parkinson’s.

Please note that this post was updated on October 5.

Kate Kelsall
Attended: Music as Pleasure and How It Can Empower You
Presenter: Concetta (Connie) Tomaino, D.A., MT-BC, LCAT, Executive Director of the Institute for Music and Neurologic Function in the Bronx, New York

"Some of the points in Connie’s presentation included:

• We all experience music, but we all feel the beat differently.
• The importance of singing songs one knows well to cue yourself (she sang “You are my ____”; the audience filled in the blank with SUNSHINE).


• The prosody (rhythm, stress and the intonation) of singing matches that of the voice.


• Songs can promote memory retrieval of past events that are associated with certain songs.


• Music and songs can help with psychological issues such as depression or fatigue.


• Choose music to move by and choose different music to lull yourself to sleep.


• People with Parkinson’s have difficulty with articulation and lack of breath support. Singing can help with these issues. She illustrated with the song “Amen," noting she was able to help her patients increase their breath support from three syllables to 19 syllables."

Learn More:
Find resources on music and PD
Watch Ms. Tomaino's video presentation from PDF 2009 educational seminar


Jackie Hunt Christensen
Attended: Non-Motor Symptoms: Sleep, Pain, and Autonomic Dysfunction

"This session gave scientific validation to symptoms that many of us with Parkinson’s disease have been experiencing for years, often without acknowledgment from our physicians. Treatments haven’t been identified for most of these problems, but having them recognized as real phenomena that Parkinson’s disease may cause for some patients is a giant step in the right direction toward better patient care.

• Sleep issues: It is estimated that 90% of people with PD will experience some sort of “sleep disturbance.” These can include reduced sleep; sleep fragmentation (waking up a lot during the night); Rapid Eye Movement (REM) Sleep Behavior Disorder (acting out our dreams, such as kicking, punching, screaming); or excessive daytime sleepiness. Some of these conditions can be worsened by PD medications.

• Pain: Two-thirds of PD patients report pain that is directly related to their PD symptoms. This pain can occur in arms, legs, back, shoulders and usually occurs on the side of the body most affected by PD. It may improve after PD drugs are begun. Some people with PD may feel pain in a situation or experience that is painless for those without Parkinson’s. Others may feel extreme pain when people without PD feel only mild discomfort.
  

• Autonomic dysfunction: The autonomic nervous system regulates “automatic” body functions. For those of us with Parkinson’s disease, autonomic dysfunction can include bladder problems; constipation; sexual dysfunction – in both women and men, excessive sweating, and sensitivity to cold."

Learn More:
Find resources for nonmotor symptoms in PD
Watch PDF's online seminar on nonmotor symptoms

WPC Science Day Two: Genetics Updates

From James Beck, Ph.D., Director of Research Programs

Here are some additional scientific updates from this week's 2nd World Parkinson Congress (WPC).

Michael Schlossmacher, M.D., reported the results of his recent experiments that demonstrate that mutations in the GBA gene, which were recently identified as a major risk factor for Parkinson's disease (PD), actually contribute to an increase in the levels of alpha-synuclein in nerve cells. Alpha-synuclein is the protein that accumulates in dying nerve cells and is the hallmark of Parkinson’s disease. This result provides a biological explanation as to the significance of these GBA mutations and their relevance to PD. That is to say, Dr. Schlossmacher has shown how mutations in the GBA gene are related to an increased risk of PD. His work has gone through peer review and is currently awaiting publication—we will let you know when it is published and report on his findings in more detail.

Additionally, Haydeh Payami, Ph.D., a research scientist from the Wadsworth Center and Director of the NeuroGenetics Research Consortium in New York State, reported late-breaking results of the re-analysis of a large-scale genetics study her team published this past March in Nature Genetics. The re-analysis examined whether there was a genetic interaction with the onset of Parkinson’s disease and the amount of coffee study participants consumed. Her team found a strong link with a particular gene called GRIN2A, which makes one component of the receptor protein that binds to an important neurotransmitter called glutamate. When this receptor protein binds too much glutamate, it becomes over-activated and can lead to cell death.

What is the role of coffee? Well, the caffeine in coffee indirectly alters how much glutamate is released from neurons by blocking the function of another receptor protein—the adenosine A2A receptor. This in turn, may prevent the cell death observed in the presence of too much glutamate. Indeed, epidemiological evidence suggests that coffee drinkers may have a lower risk of PD. However, Dr. Payami introduced a wrinkle in this concept. She suggests that her teams’s genetic data reveals that only some people may benefit from the strategy of blocking the A2A receptor. You see GRIN2A comes in two forms and only 25 percent of the population have the version which Dr. Payami suggests is beneficial.

Please keep in mind that Dr. Payami's study results were part of a late-breaking science presentation at the WPC, meaning the results were fresh from the lab and will need to be validated and reviewed by her peers. So as compelling as the results are, it will be interesting to see if these findings will stand after a critical examination has been performed. Whether her hypothesis regarding which form of GRIN2A is important is right or wrong, she raised an a critical issue that may be impact future drug discovery—the significance of genetically characterizing research participants. We are all genetically different, so is it so surprising that some people respond better to certain drugs than others? Maybe this is why many drugs fail clinical trials? What do you think?

As the science advances, you can count on PDF to keep you updated.

WPC Science Day Zero: Orthostatic Hypotension

From James Beck, Ph.D., Director of Research Programs

Yesterday, an industry-sponsored session for clinicians and scientists was held prior to the official start of 2nd World Parkinson Congress. Largely a review of current medical management of PD, the session included one tidbit that I found particularly interesting - a comment made by Mark Stacy, M.D.

He said that orthostatic hypotension, that is low blood pressure upon standing, is the most common, unrecognized symptom of PD.

Up to 40 percent of people with PD experience orthostatic hypotension. Drugs that are currently approved to treat hypotension, like midodrine, work, but may work too well. The problem for people with Parkinson's is that their blood pressure is generally normal upon lying down or sitting, and problematic only when standing. But midodrine is not “smart” enough to figure this out. So while the drug fixes the problem of low blood pressure when a person is standing up, it also acts when a person is not standing, often causing the problem of hypertension, i.e., high blood pressure.

A solution may be in the works in the form of a drug called droxipoda, approved in Japan and under clinical development in the US by Chelsea Therapeutics (one of the industry sponsors of the session). Much like levodopa, or L-DOPA, a dopamine precursor given to replace dopamine, droxidopa or L-DOPS, is a precursor to the neurotransmitter norepinephrine and is given as its replacement. Preliminary evidence from clinical trials, presented by Phillip Low, M.D. from the Mayo Clinic in Rochester, MN, seems to indicate that droxidopa may benefit orthostatic hypotension in PD without causing hypertension when a person is not standing.

It will be interesting to follow the fate of this drug as it is tested. Do you agree orthostatic hypotension is a problem? Are you waiting for better treatment for it? Let us know in the comment section below.