Old Drugs – New Cures?

From James Beck, Ph.D., Vice President of Scientific Affairs

Using old drugs as new cures seems like a surefire winner. It may be. However, after attending a recent meeting outside London hosted by the Cure Parkinson’s Trust, a small yet impactful British charity, it is clear that this path is neither clear nor easy. A committee of experts at the meeting evaluated and prioritized dozens of existing compounds – many are drugs used to treat other diseases – based upon their potential to stop Parkinson’s disease.

From left, James Beck, Tom Isaacs, and Steven DeWitte at
Cure Parkinson's Trust meeting at Cumberland Lodge.

Repurposing drugs for a new use like this has the potential to shave significant time from the drug development process for Parkinson’s. But existing drugs come with existing problems. And these problems cannot always be overcome. For instance, a recent science article covered by PDF suggested that a chemotherapeutic agent, nilotinib, might be useful for treating PD. However, it is not clear what the proper dose should be (the article suggested a low one would be effective). Moreover, with potential side effects that include sudden death, the committee felt it was not ethical to consider placing people living with PD in potential danger.

Still, there are drugs that appear to be safe and well tolerated, like statins used to lower cholesterol and metformin used for type II diabetes to name a few. These drugs are not chosen at random: By surveying thousands of people, epidemiology studies have been able to link drugs people take for other conditions (like these) with a lower risk of developing PD. There are also data from laboratory studies that suggest how these types of drugs may help. Even here, though, the path forward is not so clear. The mechanism of action, that is how might some of these drugs actually affect PD in people, is not known. This is not always a stumbling block; but when combined with drugs that are likely to have modest effects and low odds of success, it can be a problem, especially with limited resources.

Recognizing these issues, the Trust’s prioritization committee took a hard look at each potential drug candidate and recommended a handful as most promising. These few culled from a list of two dozen compounds will now advance towards evaluation in clinical trials. Hopefully, that phase will begin soon.

BigBrain - What Does It Mean?

From James Beck, Ph.D., Vice President of Scientific Affairs

This blog is part two in a series of three about the BigBrain.

Several weeks ago saw the announcement of a description of a new and highly detailed atlas of the brain, called BigBrain.  PDF wrote about how one person, making the decision to donate their brain, has made a significant contribution to science.  Indeed, that is true.  But what does this really mean for the future of neuroscience … and Parkinson’s research?

1. BigBrain is like the Google Earth of the brain, allowing researchers to not only see the big picture of brain anatomy but also allowing them to zoom in with incredible resolution to practically see individual cells.
2. Although BigBrain is like Google Earth, it currently does not have any labels.  That is, if you do not already know what you are looking at, BigBrain will not be able to help you.  (Is that New York City or Jersey City that I see?) Not all scientists are experts in neuroanatomy and so not everyone looking at BigBrain can delineate every brain structure.  Besides, annotating BigBrain will only need to happen once.  As this is done over time, researchers of all stripes will be able to ask interesting questions.
3. BigBrain is helpful, but it's just that: one person’s brain … Just like the first genome sequenced in the Human Genome Project was just one person’s DNA.  Half the battle here has been establishing the procedures to actually create a BigBrain.  As more courageous individuals donate their tissue, scientists will be able to generate more BigBrains in order to capture all the individual variation that is in each of our heads.

In sum, BigBrain is what they call “enabling technology.”  On its own it does not do much, but when combined with other technologies it is a powerful tool that can move science forward.  Thinking what the personal computer or the Internet have done recently, it will be exciting to see how this will change neuroscience.

(A view from the BigBrain atlas. The substantia nigra, where dopamine neurons are lost in PD, are the dark bands located below the two dark circles in the center.)

Righting the Clinical Research "Enterprise"

By Ronnie Todaro, M.P.H., Director of National Programs

When opening the Sunday Review section of the New York Times this past weekend,  I did a double-take as a topic of much discussion here at PDF was featured front and center - trumping commentary on the state of the economy, international relations and the latest political debate.

"Do Clinical Trials Work?," by Clifton Leaf serves as a primer on some of the key issues that prevail within the clinical research enterprise - the tension between scientific inquiry and patient priorities; the odds that study sponsors take when betting on the success of a potential therapy; and the disconnect between those who participate in a study and those who may actually benefit from the treatment being tested. It also serves as yet another wake-up call on why people who are living with a disease, be it cancer, Alzheimer's or Parkinson's, need to be formally included in research decision-making.

I can't help but wonder, would clinical research be in a different state if people who actually had the disease were sitting around the table, eye-to-eye with researchers, study sponsors and federal regulators? Would their presence and perspective change the priorities and processes of clinical research? Would it create the sense of urgency that occurs when the personal is married with the professional?

Of course, we here at PDF would  answer in the affirmative as would our 200 Research Advocates across the country.  The bottom line - we can right this "Enterprise" - but only if we recognize who should be at the helm - the patient.

Going 3D: The BigBrain Is A Gift That Keeps on Giving

This blog is part one in a series of three about the BigBrain.

Do you remember the moment of putting on 3D glasses in a movie theater? There was awe and excitement as stories and images that were flat came to life. There was similar excitement yesterday when researchers reported in Science that they have created BigBrain, a high resolution 3D digital image of the brain.

To understand the excitement, it’s important to understand that like a 3D movie, this image isn’t simply a flat picture of the brain. It is incredibly in-depth. Have you ever had an MRI? Well this is hundreds of thousands times more detailed.  Some have compared BigBrain to Google Earth, which shows much of the globe, piece by piece. Scientists think this up-close-and-personal view will help us understand how the brain works.

But perhaps the most amazing part of the BigBrain story, is the one of how it came to be. BigBrain was reconstructed from a real donated brain, from a 65-year old woman who had passed away. She gave her brain to science, and now we may all benefit for years to come.

For it’s true that the brain truly is the final frontier. Did you know that even with BigBrain, brain donation remains an urgent need for understanding PD?

We can study other organs while a person is alive, but we cannot easily access and view a brain. The only way to study to do so to date has been to study brains donated to science. Brain donations enable scientists to learn more, for example by comparing a person’s medical records and PD symptoms, to their brain tissue after death.

That said, brain donation often brings up many questions and concerns for people with PD and their families. A few years ago, PDF Research Advocate Diana Barnwell wrote a beautiful story, "My Last Gift", about her decision to donate her brain to research, which may provide food for thought.

What’s your view of brain donation, and of this gift that made BigBrain possible?

At PDF, we always say that we can’t do our part without you. And in looking at BigBrain as an example, it’s true. In fact, this brain is only the first to be mapped. Scientists report planning to map other donor brains, including a male brain and others whose donors lived with certain diseases or conditions.

This emphasizes that it's your participation in research – including via brain donation – that brings us closer to solving Parkinson’s. So we say thank you to the anonymous donor that made BigBrain possible, and thank you to you.

Learn about brain donation by reading Diana's story, "My Last Gift," here, or by browsing PDF's list of US brain banks here.

Of Patents and Parkinson's

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

Should or could a human gene be patented? On June 13th, the Supreme Court of the United States delivered their unanimous ruling regarding what has been called the Myraid Genetics case.  The plaintiffs in this case sought to invalidate Myriad’s patent on two genes that when mutated can lead to a significant increased risk of breast and ovarian cancers.  Because of the patent for these two genes, Myriad, a clinical diagnostic testing company, was the only entity that was permitted to perform the clinical tests that can both inform women if they carried mutations in these genes and if they are at an elevated cancer risk.

In their ruling, the Supreme Court concluded that naturally occurring genes, like the ones in the patent held by Myraid, are a product of nature and therefore are not eligible for patent protection.

The emphasis of the Court is on naturally occurring genes and that is important because the Court made clear that almost any modification to that naturally occurring gene would be eligible for patent protection—provided it met all the regular standards of a patent.  The example the Court provided was for the ‘cDNA’ sequence of a gene.

When a Gene is Not Natural
So what is cDNA anyway?

It may helpful to think of the genes found in most animals as magazine stories. These stories are constantly interrupted by advertisements, forcing them to span dozens of pages instead of just a few.  These interruptions to the gene story are called introns and, just a like a real magazine story, they get skipped by the body as it reads the gene when making a protein in a process called transcription.  In the laboratory, this “ad-free” or more precisely “intron-free” version of the gene can be converted back to DNA (the cDNA) for later use in a biotech setting.  Because this edited version of the gene did not appear in nature, it is eligible for patent protection.

What Does This Mean?
In general, this decision will not really affect much in the normal operation of science and business.  Whenever a gene is patented, the ad-free cDNA version is almost always included as part of that patent.  Importantly, it is this cDNA version that is really of the utmost value to a company because the naturally occurring sequence is often so large and unwieldy it is not practical to use—this is because the cDNA form can easily be just one-fifth the size of the naturally occurring gene. That is a lots of ads that were cut!

For companies that have a product that relies almost exclusively on the naturally occurring sequence, say for a diagnostic test, this ruling will be more disruptive.  In fact, several competitors have just announced that they will offer the same cancer gene test for less than what Myriad charged.

Ok, so what does this mean for Parkinson’s disease?
Again, not much really.  There are several companies that have been trying to develop gene therapies for treating Parkinson’s.  While the patents these companies may hold on the naturally occurring gene sequence is likely not enforceable anymore, the shortened version of the gene still has a valid patent and that is what counts—it is this shortened form that is actually used in the experimental therapy.

While the Court’s ruling that naturally occurring genes are not patentable is certainly historic, I think the initial effects are relatively limited, especially for Parkinson’s.  Time will tell how this ruling will be applied to other areas of intellectual property law.

Expression vs. Insensitivity: A Message to Kanye West from a Person with Parkinson’s

From Tom Palizzi
Chair, PDF People with Parkinson's Advisory Council



Kanye West is without question a richly talented and multifaceted artist. With utmost respect for freedom of expression and the inherent controversial nature of art in general, there is, however, a fine line between expression and insensitivity.

"On Sight," the opening track on Mr. West's new album Yeezus, includes the lyrics:

“The monster about to come alive again/
 Soon as I pull up and park the Benz/ 
 We get this b*** shaking like Parkinson’s”

Many of us appreciate the lighter side of having a chronic and degenerative movement disorder, though as many interpret such statements as harsh and insensitive. While it appears Mr. West is familiar with one of the more recognizable symptoms of Parkinson's disease, there are several other, less obvious challenges people with Parkinson's face.

For more than 55 years, the Parkinson's Disease Foundation (PDF) has been helping people understand and cope with Parkinson's disease. In a unique and bold move, the foundation formed the People with Parkinson's Advisory Council (PPAC) to ensure the effectiveness of their actions.

As Chair and on behalf of PPAC, I would be delighted to help Mr. West better understand the truths and myths of "Parkinson's" and how it indiscriminately impacts the lives of roughly 1,000,000 Americans and their families. Notable people such as Michael J. Fox, Muhammad Ali and Ben Petrick, my peers and millions of others are testament to the enduring spirit of people with Parkinson's.

Mr. West, please take a moment and visit www.pdf.org to learn more and, by all means, feel free to contact me or my colleagues with any questions.

Respectfully,

Tom Palizzi
Chair, People with Parkinson's Advisory Council

From PPAC: Parkinson's Isn't Newsworthy ... Until It Personally Touches You

By Peggy Willocks, member, PDF People with Parkinson's Advisory Council

April is Parkinson's Awareness Month. And it won't be newsworthy that I came all the way from Tennessee to New York to participate in this past Saturday's Parkinson’s Unity Walk, where about 10,000 people with Parkinson's, friends and family "walked" through Central Park as a symbolic gesture to raise funding for research.

As a member of the Parkinson's Disease Foundation's (PDF) Advisory Council, it isn't newsworthy that I am also here as a voice of the patient in helping to have better and faster approval of therapies for the debilitating illness. PDF adopts the promise of a cure by creatively incorporating the opinion of those who actually live with the disease into the research program. After all, who wants to find a cure more than the patient? We met with PDF, the oldest established Parkinson's non-profit organization, for the final two days of last week.

But it should be newsworthy that Lizzie Graham was there from across the pond. Graham is Director of Fundraising and Global Communications of the European Parkinson's Disease Association (EPDA) from the UK. Maybe with the two group's collaboration we will make some headway.

What does it take to be newsworthy? Finding a cure would definitely be great news. The gold standard treatment is a pill discovered over 40 years ago. We won't find a cure this year. One reason is the cutting of funding from the NIH budget due to sequestration. Another is the lack of participants in clinical trials for Parkinson's.

It isn't newsworthy that this year marks my 20th year with the disease. But it may be newsworthy that this is my 13th year of having been one of six people in the world who allowed transplantation of retinal cells into my brain from a donor eye in hopes of producing dopamine, the chemical my brain lacks. However, the trial was halted several years later due to not meeting its endpoints.

Parkinson's is more than a tremor or immobility. Many are plagued with non-motor symptoms such as depression, psychosis and dementia, creating an economic burden of over $14 billion. Living with Parkinson's isn't a death sentence; it is a life sentence.

I hope I live to see the cure - now that would be newsworthy.

Peggy Willocks of Johnson City, TN, is a member of the PDF People with Parkinson's Advisory Council. Learn more about her work in the Parkinson's community by reading her biography on PDF's website here.