The Latest Research And Treatment Options For Parkinson's Disease

MS. DIANE REHM

10:06:53
Thanks for joining us. I'm Diane Rehm. Parkinson's disease affects 1 million people in the U.S., nearly 10 million people worldwide. Public awareness of the neurological disorder has increased thanks to actor Michael J. Fox who stars in a new TV show about a man living with Parkinson's. Joining me to talk about the reality for most patients and the latest treatment options: Story Landis of The National Institute for Neurological Disorders and Stroke, Dr. Zoltan Mari of Johns Hopkins University Medical Center, and, joining us by phone from New York City, neuroscientist Todd Sherer.

MS. DIANE REHM

10:07:43
He's chief executive officer of the Michael J. Fox Foundation. I do invite you to join us as well, 800-433-8850. Send us your email to drshow@wamu.org. Follow us at Facebook or send us a tweet. Welcome to all of you. Thank you for being here.

DR. ZOLTAN MARI

10:08:08
Thank you. Good morning, Diane.

DR. STORY LANDIS

10:08:10
Delighted to be here. Thank you for asking us.

DR. TODD SHERER

10:08:13
Thank you. I'm glad to participate.

REHM

10:08:15
And let's start with you, Dr. Mari. Explain to us what Parkinson's disease actually is and how it begins.

MARI

10:08:27
So Parkinson's disease is a neurodegenerative disease. It is a progressive neurological condition that often starts with certain motor problems, movement control issues. It could be a little tremor, loss of dexterity, slowness or balance problems. And for the longest time, it has been recognized as a movement disorder because of those signs that oftentimes come on early.

MARI

10:08:52
However, more recently, we recognized that it's not only a motor disorder. There's a very significant non-motor component as well, such as anxiety, sleep problems, depression, panic disorder, many other things that are not necessarily a movement control issue but relate to non-motor behavioral problems, which could be quite disabling, especially more advanced stages.

REHM

10:09:16
Are we seeing more of Parkinson's, or are we simply hearing more about it?

MARI

10:09:25
I think it may be both. There are some data to suggest that actually there is an increasing prevalence of Parkinson's disease. There are a couple of factors to that. One may be the fact that we are an aging population, and the incidents of Parkinson's disease is age-related. So the older the population is, the more we're going to see of it.

MARI

10:09:49
Over 60 years, it's about 1 percent of the population affected. So hundreds of years ago when the life expectancy was 40 years, obviously there were fewer individuals to have had a chance to get to that age range. So that's part of it, but there may be other factors as well that are somewhat exploratory and under investigation.

REHM

10:10:13
Other factors, Dr. Story Landis?

LANDIS

10:10:17
So one of the possibilities is that there are environmental influences which represent risk factors. Thirty years ago, everyone was convinced that Parkinson's disease was caused by things in the environment. That came from the observation that, after the flu epidemic in 1918, there were many cases of (word?) encephalitis, which exhibited itself as Parkinson's.

LANDIS

10:10:50
And then the observation that if you made a synthetic opioid incorrectly, you ended up with a toxin which killed dopamine neurons, which are lost in Parkinson's, and gave rise to the frozen addict phenomenon. But more recently, there are epidemiological studies which show that exposure to particular solvents can cause Parkinson's disease as can the exposure to pesticides or even herbicides and also traumatic brain injury can increase...

REHM

10:11:24
And when you talk about these pesticides, herbicides, what are you talking about, things like DDT that have already been banned or those that are even now on the market?

LANDIS

10:11:40
There are a number of those which are still in use. And, in fact, the data that support the role of pesticides, epidemiological data, come from studies of farm workers in the Central Valley of California.

REHM

10:11:53
The thing I want to say up front is that my own husband has had Parkinson's for the past eight years. He is now in assisted living. His began with, as you suggest, Dr. Mari, just the slight shuffle and physical symptoms of that sort. Dr. Sherer, do we know absolutely what happens in the brain when Parkinson's begins to exhibit itself?

SHERER

10:12:38
We don't really. Most of the motor symptoms of Parkinson's that we've been talking about are due to the loss of cells in the brain that produce a very specific protein -- chemical that's called dopamine. And we can treat a lot of the motor symptoms then by replacing the dopamine in the brain using some drug treatments.

SHERER

10:13:02
But we know that there's a lot more going on in the brain, and we also know that by the time someone is first showing those motor signs, the slight motor signs that Dr. Mari described, there's been already a significant degeneration or loss of cells in the brain. So the concept is actually that the disease process is probably beginning in the brain years before the demonstration of any of the symptoms.

REHM

10:13:32
And yet, Dr. Mari, you talked about the older population, the fact that we are an aging population, and yet, at the same time, you see Parkinson's appearing earlier and earlier. And, of course, Michael J. Fox is one of those people. How do you explain that, Dr. Mari?

MARI

10:14:00
So the age of onset is a spectrum. There are variations. The average age of onset is 62 years, but that means that patients may come down with Parkinson's disease earlier ages and later ages. I recently saw a gentlemen who was 79 at the onset of Parkinson's disease, which is very unusual. But then there are patients who come down at an earlier age.

MARI

10:14:25
I have a patient who first developed symptoms at age 11, and that patient happened to have a mutation, a PARK2 mutation, as well as a PINK1 the same time. So certain genes will make it much more likely to have the Parkinson's disease presented at an earlier age.

REHM

10:14:46
Genes that are inheritable.

MARI

10:14:50
These genes are inheritable, but they don't have what we call 100-person penetrates. So none of the Parkinson's genes at the moment will mean a certainty that you will have the Parkinson's disease. Like, in Huntington's disease, if you have the abnormal gene, it's just a question of time before you have the disease.

MARI

10:15:08
Whereas in Parkinson's disease, no matter which one of the genes -- because there are multiple -- you have, you may still live an old age and not have Parkinson's disease, which speaks to the factors that Dr. Landis pointed out in the environment. So there may be an interaction between the genes and the environment, or it may be an interaction between many different genes that will ultimately determine when you're going to come down with the symptoms or if you're going to develop Parkinson's disease at all.

REHM

10:15:35
Dr. Landis, how much is NIH doing on Parkinson's these days?

LANDIS

10:15:43
We're doing a great deal, although, to be honest, it's not as much as we'd like to be doing.

REHM

10:15:50
How much money has been allocated?

LANDIS

10:15:53
So the NIH is in FY-12, which is the last year for which we have good figures, invested $154 million. The number for FY-13 will almost certainly be less than that because, as you know, due to the sequester, the NIH lost $1.5 billion from its budget. We don't actually allocate money to any particular disease. We balance the scientific opportunities and the need and invest the money as wisely as we can across all the different diseases for which we are responsible.

REHM

10:16:34
Though the symptoms, the outward symptoms, may be totally different for Parkinson's and, for example, Alzheimer's, Dr. Mari, what do you see in the brain that's different for Parkinson's?

MARI

10:16:55
So, for instance, Alzheimer's disease is a slightly different kind of a neurodegenerative disease where it is susceptible neural populations that are attacked by this neurodegenerative process are different from Parkinson's disease. And, ultimately, we believe that pretty much every neuron in the brain at one point will be affected, but the one that are affected first will be different between different diseases.

MARI

10:17:22
And as Dr. Sherer pointed out, the dopamine neurogenic cells in Parkinson's disease have been recognized very early on and somewhat specific to Parkinson's disease. There are some specific susceptibility of these dopamine neurons provide they go first, and that relates to the motor control and what we discussed earlier.

MARI

10:17:44
But as the disease progresses, more and more neural populations or cell populations get affected, and that brings new and different symptoms, including non-motor symptoms, memory problems, et cetera. In Alzheimer's disease, it is the structures and networks that are responsible for memory and cognition are the ones that are attacked first, and that's how the presentation, clinically, appears different.

REHM

10:18:10
So what you're saying is that the order of presentation is what determines whether one is diagnosed with Parkinson's or one is diagnosed with Alzheimer's.

MARI

10:18:24
Pretty much. But at the same time, there are clear molecular differences also. So if you go ahead and do some microscopic evaluations, you will see differences.

REHM

10:18:34
And we'll get to more of those differences after a short break. We'll take your calls, 800-433-8850. Stay with us.

REHM

10:20:02
And welcome back. Here is our first email for Story Landis who's at the National Institute for Neurological Disorders and Stroke. Dr. Zoltan Mari, he's interim director of the Movement Disorder Center at the Johns Hopkins University School of Medicine. And with us by phone, Todd Sherer. He's chief executive officer of the Michael J. Fox Foundation for Parkinson's Research.

REHM

10:20:38
Here is an email from Lola. She's in Bethesda, Md. "I'd like to know," she says, "if there's any knowledge about Parkinson's and frontal lobe dementia. My husband began to exhibit inappropriate behavior almost as soon as he was diagnosed with Parkinson's in 2004. One of the first things we noted was his lack of empathy. He became abusive, used obscenities, which he had never done before. He also began to engage in compulsive eating. He became unaware of people around him. Eventually, he became violent. He's now in a nursing home." Dr. Landis.

LANDIS

10:21:34
That's very sorry to hear of his progression. There's nothing that precludes a particular person from having more than one neurodegenerative disease at the same time. In fact, when you look at brains of patients who died with a diagnosis of Alzheimer's, it's very common to find a mixed dementia. The most common mixed dementia is the pathological finds of Alzheimer's with tau protein aggregates and amyloid deposits in addition to the kinds of changes that we recognize as the consequence of vascular dementia. That is...

REHM

10:22:19
So it can all merge at the same or different times.

LANDIS

10:22:25
Right. There are -- in that case, there are two difference processes which are leading to the loss of populations of nerve cells.

REHM

10:22:33
But how common is the behavior she describes, Dr. Mari?

MARI

10:22:39
So I would like to add that it is also possible that it's frontotemporal dementia from the get-go. As I mentioned, the so-called non-motor systems are part of Parkinson's disease, but they're very unlikely to present early. So if she describes that these behavioral problems presented in the first year, my suspicion that it is not Parkinson's disease, as frontotemporal dementia, Lewy body disease, even Alzheimer's disease can produce Parkinsonism, which is not Parkinson's disease.

MARI

10:23:08
It's not the Parkinson's disease pathology. It's the appearance of Parkinsonism, shuffling gait, tremor, slowing. That can be seen in frontotemporal dementia. The early onset of the severe non-motor problems would raise the suspicion for FTD but also for Lewy body dementia, which by definition should have these significant non-motor behavioral problems within the first year of the appearance of motor Parkinsonism.

REHM

10:23:37
You know, what worries me is that sometimes patients diagnosed with Parkinson's disease can be given medications that may bring on those kinds of problems. For example, Requip is one of those, Dr. Mari.

MARI

10:24:01
Absolutely. We are balancing some of the side effects caused by the symptomatic therapy to treat the motor problems. And these side effects can be quite disabling as well. Every patient is different in their response both from the benefits' perspective as well as the side effects perspective may differ.

MARI

10:24:22
So we sometimes try Requip. If that causes problems, fortunately, we now know what those are because at first the impulsive behaviors were not disclosed and not known to the clinicians. And that caused a lot of problems. Now we know the spectrum of side effects, and we are prepared. And if you're seeing them, we scale them back or discontinue the drug. And therefore we get rid of the side effects, and we try something else.

REHM

10:24:47
All right. Dr. Sherer, I'd like to know the goals of the Michael J. Fox Foundation for Parkinson's Research, what you're doing, where you believe you're headed.

SHERER

10:25:03
Sure. Thank you. So the Michael J. Fox Foundation was founded in 2000 by Michael J. Fox with a pure mission of trying to accelerate research towards a cure for Parkinson's disease. So our primary focus is to understand the needs that people living with Parkinson's disease have and then to support the research to lead to new treatments, to improve the quality of life of people living with Parkinson's and ultimately a cure for the disease.

SHERER

10:25:35
We have grown over the last 13 years, so we're now the largest nonprofit funder of Parkinson's research, funding over $350 million in Parkinson's research. And in parallel to trying to develop new treatments, both for the symptoms and then for something that could slow the progression, we're also working on a number of challenges across the field that impact our ability to do that. And one of the things that we're working on a lot -- actually also in collaboration with the work at NIH that's relevant to the last discussion -- are better markers and tools for the diagnosis and tracking of the disease.

SHERER

10:26:17
Right now, Parkinson's disease diagnosis, as was just discussed, is purely based on a clinical evaluation. And it's not 100 percent accurate. And that can have an impact both for the current treatment of the disease, as was just discussed, where people could be put on inappropriate treatment based on their diagnosis. But also, that impacts our ability to develop new treatments. So we need to be able to better identify people that may benefit from some of the exciting treatments that are in development.

REHM

10:26:48
And before we get to some of those treatments, talk about Michael J. Fox, how long he's had Parkinson's. And I think a lot of people are wondering how and why he's doing so well.

SHERER

10:27:08
So Michael was diagnosed with Parkinson's in the early 1990s, so it's been probably over 20 years. Parkinson's disease is very different in different people. That's one of the things we've also talked about today.

REHM

10:27:24
Yes.

SHERER

10:27:25
Some people seem to progress more quickly. Some people progress more slowly. Also people respond differently to medication. So Michael, like many other patients, works very closely with his neurologists to optimize the use of the available medicines and, fortunately, right now, is doing very well.

REHM

10:27:46
I'm so glad to hear that, I must say. I interviewed Michael several years ago at a gala. He is the honorary chair of the Parkinson's Action Network Gala. And I must tell you, his movements at the time seemed uncontrollable. And now we see him on television in a sitcom. So I think a lot of people have questions about that, Dr. Sherer. I'm not asking you exactly what kinds of medications he's on. But to see him in this situation, I think, gives a lot of people either hope, or they're wondering what's going on here.

SHERER

10:28:46
Yeah, I mean, what you are describing in terms of some of those uncontrollable movements, those actually are a side effect of the medication. And it's kind of counterintuitive because Parkinson's disease is marked by slowness of movement. But then in response to some of the medicine, people can actually appear to have extra or be hyperactive.

SHERER

10:29:11
And it's a constant challenge for patients to balance their medicine to get the optimal benefit in terms of improving their movement without dipping into these uncontrollable side effects. And this is something that right now for Michael, finding the right dosing and interactions with his doctor in terms of optimizing his medicine, he's finding a process that is optimizing the therapeutic benefit while limiting those side effects.

REHM

10:29:40
What do you believe, Dr. Sherer, Michael is attempting to do with this program focused on a man with Parkinson's?

SHERER

10:29:52
I think first at the highest level, Michael is just going about his work. And his message sort of comes from that, in that in the face of a disease or in the face of a challenge this is just one part of who you are. And you can continue to make contributions and to do things that you really love and enjoy. And for him, he obviously loves and enjoys being on television and acting. That's his career and his passion. And I think we have seen a great response from our Parkinson's community through this example that this is just one part of who you are, but it's not everything that you are.

REHM

10:30:39
Dr. Mari, I realize you do not know Michael J. Fox. You do not know his medical history or the kinds of treatment's he's had. But how typical is Michael J. Fox in the Parkinson's community?

MARI

10:30:59
I would like to emphasize that it is true that there is quite a bit of heterogeneity within the Parkinson's population. And in terms of the rate of progression, there are patients who are much more rapidly progressive and then are some who are slowly progressive. It is unusual to do that well 20 years into the disease, but it's not unheard of. So I would say that 1 percent or less of the patients can have that wonderful functional state 20 years into the disease. I've had patients like that, but it's very unusual.

MARI

10:31:35
Now, in terms of the management making a big difference, I'd like to again confirm what Dr. Sherer said, that adjustments and being properly medicated actually can make a big difference. The National Parkinson's Foundation was involved in a study which is called Quality Improvement Initiative whereby they show that across centers of excellence there have been significant differences in outcomes, how patients were doing. And these are patients who are treated all by experts with treatments that are currently available to all of us.

MARI

10:32:11
And the difference how we are using those treatment modalities that are currently available can actually make a big difference how well our patients are doing. So that's a very important observation in considering that the majority of Parkinson's patients in the United States are treated by either primary care doctors or general neurologists. The general sense is that we can do much better as a whole to improve quality of life by appropriate treatment adjustments.

REHM

10:32:39
Dr. Zoltan Mari of the Johns Hopkins University School of Medicine, and you're listening to "The Diane Rehm Show." We have many callers waiting, and I do want to let you know that we may not be able to get to all of you today. We know you have lots of questions about Parkinson's. Dr. Mari has graciously offered to answer questions from listeners that we don't get to during the hour. So please send questions on email, Facebook, Twitter or our website, and those questions and answers will be posted later at drshow.org. Let's go first to Columbus, Ohio. Hi there, Bob, you're on the air.

BOB

10:33:43
Hi, how are you?

REHM

10:33:44
I'm fine, thank you.

BOB

10:33:47
That's good. I called because I have Parkinson's. I was diagnosed in 2000. I had DBS surgery in 2006. And now, even though my voice is weak, I can still do Tai Chi every day, and I teach a Taekwondo class for kids still. And I've been standing on one foot since you called my name.

REHM

10:34:18
Bob, I'm so glad that you're doing so well and that you are continuing with your Tai Chi. He talked about deep brain stimulation, Dr. Landis. And that has become somewhat controversial. Talk about the uses where it makes sense and where perhaps it does not.

LANDIS

10:34:45
So deep brain stimulation is a treatment that is often suggested to patients who are in the mid-stage of the disease and are no longer well controlled by treatments which replace dopamine. NINDS, in collaboration with the Veterans Administration, ran a trial comparing DBS with best medical treatment and provided -- and that trial provided compelling evidence that in fact for many patients DBS was of significant benefit, better than just best medical treatment. And there are examples of patients whose lives have been transformed.

LANDIS

10:35:25
One of the critical issues is where in the brain the stimulating electrodes are placed. In some cases placement isn't optimal and there are side effects rather like those which were described for Requip with compulsive behaviors. And we don't have long term follow up of those patients yet who have gotten DBS.

REHM

10:35:52
Interesting. And how long would you like that follow-up to be?

LANDIS

10:35:58
Well, the NINDS and the VA are following those patients who were initially followed for three years for an additional five years in order to look at the long-term cost benefit analysis.

REHM

10:36:12
Do I understand correctly, Dr. Mari, that once the physical symptoms have begun that deep brain stimulation only works on those movement parts of the disorder?

MARI

10:36:32
That is generally correct. And that underlines the important of patient selection because DBS is a symptomatic therapy. It is excellent to treat certain symptoms and can really be life changing, just as Dr. Landis mentioned.

REHM

10:36:47
OK. Tell me about those symptoms.

MARI

10:36:50
So, for instance, if somebody as tremor and that is very disabling to them and sometimes it is not very well controlled with medication, DBS can still help. Another very good example is, as Dr. Landis pointed out, at a certain stage of the disease we are no longer able to control the patient's functionality with adjustments of their drugs only.

MARI

10:37:14
And that is because the so-called therapeutic window is narrowed. So the patients need more and more of the medications to be able to move and move around, but it takes less and less for the medication to cause these jerky movements dyskinesias. Those are great patients for DBS.

REHM

10:37:31
All right. And a short break here. When we come back, more of your email, your phone calls. Do join us, 800-433-8850.

REHM

10:40:01
And welcome back. We'll go right to the phones to Susan in Cary, N.C. Hi, you're on the air.

SUSAN

10:40:11
Hi, Diane, thanks so much for taking my call.

REHM

10:40:13
Certainly.

SUSAN

10:40:13
My father was just recently, a couple weeks ago, diagnosed with Lewy body dementia. I had never even heard of it. And my understanding is that it's an Alzheimer's and Parkinson's type of mix. So it's, like, the, you know, the best of both worlds. And I just was wondering if we could speak about why most -- why we always -- I know we hear about Alzheimer's and Parkinson's, and that's where the research is going.

SUSAN

10:40:43
But you never hear about LBD. Is the Michael J. Fox Foundation -- do they focus at all on LBD? And as well as -- I know you touched on it just a little bit ago, but about the medications and how it does affect each patient individually and how there are severe side effects.

REHM

10:41:00
All right. All right, Dr. Sherer, I'll start with you.

SHERER

10:41:06
Sure. Well, thank you, Susan, for the call. And so one of the things that we have been talking about is actually, I think, these diseases are all operating on a continuum, and there's some very similar processes going on in the brain and the underlying difficulties that are facing the physiology. And the diagnoses is still sort of unclear, so it depends somehow -- sometimes on what symptoms are being expressed at what time of the disease.

SHERER

10:41:39
In terms of our work at the foundation, many of the therapeutic strategies that are being developed for all of these Parkinsonism types of diseases will potentially have impact across the different diseases. So Parkinson's disease itself could sometimes be marked by cognitive problems. Lewy body dementia has mostly the same underlying biological problems that are happening in Parkinson's. So there's a lot of interaction and cross talk about the research that is going on across these diseases.

REHM

10:42:13
And, you know, we haven't talked about the symptoms of freezing in the same extent that we've talked about the tremors, Dr. Mari.

MARI

10:42:25
So freezing of gait is a common problem in Parkinson's disease, a difficult problem. Gait impairment and disorders include balance problems, slowing, many other things, but freezing of gait in particular is hard because oftentimes it is medication resistant. So the medications that otherwise help symptomatically with many other things won't really help freezing of gait. And, at the same time, as we discussed DBS, which could be so helpful in many things, it may not be helpful for everything. And freezing of gait tends to be one resistant problem, such as speech, as the gentleman earlier noted.

REHM

10:43:04
His voice muscles were weakening or freezing?

MARI

10:43:10
The muscles that create sounds are very a highly coordinated and sophisticated manner and that coordination is affected by Parkinson's disease. You're not able to project as well the -- it becomes hypo phonic or the volume of the voice goes down, but in more severe cases the articulation can also become a problem. So it's a combined speech problem in Parkinson's disease.

REHM

10:43:38
And isn't there also ultimately, Dr. Landis, a swallowing problem?

LANDIS

10:43:45
Yes, absolutely. And there are efforts to develop devices that will enable Parkinson's patients and other patients with swallowing problems to be able to swallow because, if you don't swallow, you will have the potential of pneumonia.

REHM

10:44:02
All right. Let's talk about going forward, what you're all hoping for. Here's a tweet from John who says, "I'd like to know more about intestinal gel for Parkinson's that's currently in research in the U.S." Is that correct, Dr. Mari?

MARI

10:44:24
Yes, that is correct. It is under investigation in clinical trial. In some other parts of the world, it is already approved treatment. Basically it is just a different way of administering Levodopa, the name of this...

REHM

10:44:38
Ordinarily known by the name of Sinemet taken orally.

MARI

10:44:41
Sinemet is the most well-recognized brand name, but there are other drugs that have Levodopa, such as Stalevo and others, Parcopa. But nevertheless this treatment modality -- it's called LCIG or levodopa-carbidopa intestinal gel -- is delivered to a tube into the stomach which actually goes beyond the stomach and releases the gel in the intestines from a cartridge that the patient wears.

MARI

10:45:09
And that has a tiny motor that controls the rate as the gel is delivered. The reason why this is very good is because part of the disability, patients in more advanced stages of the disease have, is the ups and downs, the unequal delivery of Levodopa. This helps correct that to some extent...

REHM

10:45:29
Sort of level it out.

MARI

10:45:31
And the fluctuations are reduced. And this is just a more advanced and better way of delivering Levodopa.

REHM

10:45:37
But isn't there also the possibility of infection with that intestinal tube?

MARI

10:45:43
It is an invasive treatment.

REHM

10:45:45
Yes.

MARI

10:45:45
And, therefore, all the, you know, complications and risks as associated with it. But I think most people believe that the patients who are good for this treatment, the ones that -- who fluctuate the benefits outweigh those risks.

REHM

10:46:00
Dr. Landis, what is the most exciting new possibility out there for perhaps not only treatment, but prevention?

LANDIS

10:46:14
So the Holy Grail for Parkinson's disease, as for any other neurodegenerative disease, is to stop progression and, even better, if we could prevent. And there are a number of very exciting activities underway now with the discovery of genes that can either cause Parkinson's in families or represent risk factors for people who have sporadic Parkinson's. We now have a whole series of potential targets for Michael J. Fox, for the NIH and for pharmaceutical companies to focus on to develop better treatments.

LANDIS

10:46:51
Probably the most exciting of these is LRRK2 kinase which was discovered to be the most common genetic cause of Parkinson's. And the nice thing about -- I mean, it's not nice if you have the mutation. But the nice thing for the future is that this is a -- what they call a druggable target, that there are ways that you could manipulate activity of this particular protein.

REHM

10:47:15
And how would one identify that that target is there?

LANDIS

10:47:23
So if you wanted to see if affecting that target were helpful the first place you'd start is in -- not with a patient, but with a simplified system. And the most amazing way that you can do that now is through the use of induced pluripotent stem cells.

REHM

10:47:42
I don't know what that means.

LANDIS

10:47:43
OK, so these are cells that are made by taking a piece of someone's skin.

REHM

10:47:50
All right.

LANDIS

10:47:50
So if you knew a Parkinson's patient who had a LRRK2 mutation, you'd take a piece of their skin. You'd put it in cell culture, and you would roll back its developmental clock to make it just like a human embryonic stem cell.

REHM

10:48:03
I see.

LANDIS

10:48:06
And then you can turn those pluripotent stem cells that you got from the skin into dopamine neurons -- the neurons that are first affected in Parkinson's disease -- and you can make hundreds or thousands or millions of them. And you could then use them to screen to see if you had something that you thought blocked or increased the activity of this kinase, whether or not it was really effective in these cells.

REHM

10:48:33
Dr. Sherer, what is the most exciting development that you are seeing? I know there's a research community meeting in New York even as we speak. What's the latest coming out from your research organization?

SHERER

10:48:57
So I would put this really in two categories. And one is to follow up on what Dr. Landis was just describing. Probably the most exciting opportunity we have to develop really transformative treatments for people with Parkinson's is building on our increased understanding of what might be causing the disease. So our current treatments are only able to mask the symptoms, but the underlying disease is continuing.

SHERER

10:49:27
And what some of these new genetic findings, the LRRK2, another gene called alpha synuclein, what they are telling us is things fundamental to what's causing the disease process. And we now have therapies being developed, some that have just actually reached clinical testing that are trying to correct some of these genetic changes and address that underlying disease process.

SHERER

10:49:53
And what's important is that even in people who don't carry or inherited the genetic mutation we know that some of these same genes, same proteins, are involved in everybody with Parkinson's, people with Lewy body dementia. So this is a really new, exciting area we've never really had in Parkinson's before.

REHM

10:50:16
And I do want to let listeners know that the Fox Foundation has a website where you can find clinical trials in your area. That link is up on our website, drshow.org. Let's go now to Steve in Fort Myers, Fla. You're on the air.

STEVE

10:50:44
Thank you. I just want to share a quick personal story. My father was diagnosed at age 54 with Parkinson's in 1974 and first manifested when he was on the tennis court. When a ball was coming toward him, his feet would just move up and down as quick as possible but the next step -- to make any step toward the ball wouldn't happen. And he was quite frustrated, and then he was diagnosed.

STEVE

10:51:12
And he continued for the next 16 years to work and function quite well and speak and everything, was -- you know, it wasn't -- you could tell there was something wrong, but he was under the L-DOPA Sinemet medication for several years. And then at age -- well, 1991, 16 years later, his symptoms turned for the worse.

STEVE

10:51:37
And he was having, you know, freezing -- when he would get out of a car, he would halfway get out of the car, and he would freeze. And he would sit there for, you know, for literally hours, and he didn't want anybody to help him and figured he could do it. And he would be walking or standing. And all of a sudden he'd fall down and recover right away.

REHM

10:51:52
Exactly.

STEVE

10:51:54
But anyway he died at age 74, and he did live with it for 21 years.

REHM

10:51:58
I'm sorry, Steve. Yeah.

STEVE

10:52:00
Well, yeah, for 20, 21 years, and it's interesting that, you know, the term Sinemet and L-DOPA keeps coming up. And it seems that the basic same medications, with the exception of the few you were discussing a few minutes ago, I wonder -- apparently they -- are they more effective now than they were, you know, back 40 years ago, 30 years ago and...

REHM

10:52:26
I think that's a great question, Steve, because it is the medication that we're still using, Dr. Landis.

LANDIS

10:52:34
It is the medication that we're still using. And I think that underscores the importance of moving forward to identify strategies other than symptom management. NINDS hopes to fund a trial later this year that will look at the possibility that a calcium-channeled blocker rather like the ones that people take for hypertension will slow progression. There's evidence that dopamine neurons have susceptibility to calcium-channel -- calcium overload, and this is a possible treatment for that.

REHM

10:53:09
And you're listening to "The Diane Rehm Show." Dr. Mari, you wanted to add to that.

MARI

10:53:17
Yes. I would like to inject a little bit of optimism because I think that it's not all the same. There have been quite significant advances in therapeutics, and even just Levodopa, the most potent medication for symptomatic control, it remains that. But the way it is delivered is different. As I mentioned, there's Stalevo which is a drug that combines the Carbidopa-Levodopa with another drug called Entacapone which makes the Levodopa effect longer lasting.

MARI

10:53:45
And that has been helpful in many patients' case. We discuss the LCIG as a new delivery, and there is also a new medication that is hopefully coming next year to the market, another formulation of Levodopa, and it's called Rytary, which could last even longer. So there are some steps in making the therapeutics better, and it makes a difference. However, I do agree that disease modification or prevention is the Holy Grail.

REHM

10:54:12
As we have talked about Parkinson's, Dr. Mari, there may be many young people out there whose parent has had Parkinson's. Is there any way now to determine for people at a younger age whether they have that gene or not?

MARI

10:54:36
So it is possible to screen for a number of these genes that I mentioned which have been associated with a higher risk of Parkinson's disease later in life. There is a 23andMe, a service which allows you to freely be tested. We don't usually recommend genetic testing for clinical management purposes because, as we discussed, we don't have a way of preventing or stopping it.

REHM

10:54:58
To stop, right.

MARI

10:54:59
And we will treat Parkinson's symptomatically. But if somebody wants to know, there are ways. But, again, remember and be cautious that it's not a certainty. Even if you an abnormal gene that is associated with Parkinson's disease, it is not a certainty that you will have Parkinson's disease. So that is an important limitation here.

MARI

10:55:17
But, again, it is possible to get tested. And we do do some research studies where we look for patients who have genetic abnormalities because we can learn a lot, as we discussed earlier, about Parkinson's disease in general. And perhaps this will be a way to help with the cure.

REHM

10:55:35
Dr. Landis, how optimistic are you?

LANDIS

10:55:41
I believe that we have tools now in hand that will enable us to make much more rapid progress. Dr. Sherer referred to the fact that we have a much better understanding now than we've ever had before about the biochemical and molecular factors that result in the death of neurons. And we've also made an amazing discovery in the past year that, in fact, the toxic proteins that are responsible for the death of neurons in Parkinson's disease actually move from one cell to another.

LANDIS

10:56:13
And that may explain why, with time, more and more systems are affected. This is a new insight and it gives us another target to think about in terms of blocking progression because if we could stop the movement from one cell to another that could have a profound impact on progression.

REHM

10:56:33
And briefly, Dr. Sherer, how optimistic are you?

SHERER

10:56:39
I'm very optimistic. I think we're making significant progress. I think the other thing that we're seeing, too, is that people with Parkinson's and their families are getting more involved in research, as research partners and collaborators. And that engagement is also going to help us accelerate progress.

REHM

10:57:02
Todd Sherer, chief executive officer of The Michael J. Fox Foundation, Dr. Zoltan Mari of Johns Hopkins University School of Medicine, Story Landis of the National Institute of Neurological Disorders and Stroke, thank you all so much.

MARI

10:57:27
Thank you.

LANDIS

10:57:27
Thank you.

REHM

10:57:28
And, of course, we'll be taking your questions after the program. Go to drshow.org. Thanks for listening. I'm Diane Rehm.
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