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Saturday, February 13, 2016

Kirk Gibson on His Parkinson’s Disease Fight: ‘It’s Not a Death Sentence’

February 13, 2016

On the front door of his Michigan home hangs a wreath streaked with golds and reds, matching the leaves on the changing trees surrounding it.
Inside, the man who tore through Octobers past by smashing two of the most dramatic World Series home runs of our time answers the doorbell by yanking open the door and practically leaping into view, devilish grin, twinkling eyes, greeting a visitor as if teasing a trick-or-treater.
Except, this has nothing to do with Halloween.
It is a brisk autumn evening, and Kirk Gibson is in a place he never dreamed of being, waging a battle he never planned on fighting and surrounded not by teammates and postseason scouting reports, but by a loving family and a crack team of doctors and therapists.
In April, Gibson, 58, announced he has Parkinson’s disease.
With his energetic greeting, he is demonstrating one of his voice therapy exercises.
It sounds like a singer warming up his voice by working scales pre-concert. Except, the stakes are different. Dramatically different.
“I’m not going to lie,” Gibson says. “It was like a kick in the nuts. Initially, it’s a shock. And then you’ve got to tell your family, your kids, and you start looking into it. And you don’t know how they’re going to react, and you don’t want to let them down.

Lenny Ignelzi/Associated Press
Despite hitting .154 in the 1988 NLCS, Kirk Gibson hit two home runs and drove in six runs over the course of seven games.
“It’s not a death sentence. It doesn’t have to be a death sentence. So you start looking at a course of action, and you have to implement it.
“I just took it with great vigor, I guess you could say. I wanted to do it, I wanted to do it right, I wanted to do it well, and I wanted to attack what I was up against.
“I learned to hit a curveball. At one time, I learned how to hit a screwball. But I had to really screwball this thing. Because it’s different.
“It’s a new normal for me.”
As ever, he is living his life pedal to the metal. He is attacking Parkinson’s as if ripping into that Dennis Eckersley backdoor slider in Game 1 of the 1988 World Series in Dodger Stadium. Or the Goose Gossage fastball in Game 5 of the 1984 World Series in Tiger Stadium.
October. Scene of some of his greatest triumphs.
The way he figures it, he’s got a few more fist pumps in store.
On the back door for most of the past three weeks a sign has been taped to the glass: “BIG and LOUD.”
That this man would have to be reminded to do anything big or loud at one time would have been unthinkable. Always, his was among the biggest personalities in a clubhouse. One of the loudest voices on the field.
But Parkinson’s disease steals its way into your brain, affecting the central nervous system and, in turn, motor skills and nonmotor skills alike. Cells that produce an organic chemical called dopamine begin to die off, and the effects manifest themselves in a variety of ways. Slurred speech. Rigidity. Slowness of movement that can make even walking difficult at times, affecting one’s gait. Shaking.
eople around the Diamondbacks noticed a change in Gibson’s reactions toward the end of his tenure as the team’s manager.
Initially, it often can be controlled with medication. Eventually, as the disease progresses, patients hit a wall with their medication. The dosage needs to be increased gradually, but then the side effects worsen. There reaches a point where increased medication brings diminishing returns.
One of the most notable challenges associated with the disease is called dyskinesia, which is a side effect that often becomes evident in Parkinson’s patients who have been on a medication called levodopa for a prolonged period of time. Dyskinesia is a condition with severe movement disorders caused by involuntary muscle movements.
Eventually, deep brain stimulation becomes an option for patients who have reached a critical point and with whom doctors are having a difficult time managing medication.
Gibson, according to his neurologist, Dr. Ashok Sriram, has young-onset Parkinson’s disease. It is attacking the left side of his body, and it is still in the very early stages.
“We need a crystal ball to tell [his future],” Sriram says. “People progress differently. But in general, we know people with Parkinson’s, the disease progresses slowly. We know that part.
“The reality is, it is a progressive condition and things are bound to get worse. How soon, we don’t know. But people who take it as a challenge, take the bull by the horns, take charge to make sure they are in control…those people do very well. They really do very well.
“I have a feeling Kirk is going to be one of those people with slow progression because of the intensity of his exercises.”
One of the first things the specialists did with Gibson upon his diagnosis in April, after settling on his medication, was set him up with the BIG and LOUD physical therapy programs that are common among Parkinson’s patients. They call for sweeping, dramatic gestures with your arms and legs, and a concentrated effort to project your voice. Parkinson’s naturally stifles both, so essentially you retrain yourself. Big. Loud.

On the spot, in the moment, even on a quiet evening with only Kirk and JoAnn here on the couch, it is difficult to think.
“Snake,” I say tentatively. “Wait, that’s a reptile.”
“We’ll count it,” Gibson barks. “Keep going.”
“Sloth,” I continue, eyes closed, arms out, rotating. “Saber-toothed tiger.”

Photo courtesy of Kirk Gibson
Kirk credits JoAnn, pictured at the 1,300-acre ranch Gibson shares with David Wells and Jake Peavy, with being the leader of the Gibson family.
“He’s going good,” JoAnn says.
“But he’s not,” Kirk says, telling me to stop, and explaining why I’m not: “For me, it’s a cognitive exercise. When you have Parkinson’s, it’s much tougher. You started thinking and, you know, you stopped moving your arms a couple of times.
“They give you various tests, and then they give you a rank on it. They do all kinds of things. But when you’re in there the first day and you’ve got Parkinson’s and you’re all freaked out and they ask you a question like that, it’s a bitch. I think I got two or three.”
So then,” JoAnn says, picking up the story. “After the first time he did that, when he went home and he knew he had to go back in two months and the guy was going to retest him…”
“I studied the alphabet,” Kirk says, grinning wildly. “Animals.”
“Yeah, he just started reeling them off,” JoAnn says.
“But that’s not good,” Kirk says, laughing. “They’re giving you a test for a reason. It’s just me f–king around, basically.”
“The doctor was impressed,” JoAnn says.
“He said, ‘You’ve been studying!'” Kirk says.
Damn right Gibson had been—and is—studying. He is attacking “Parky’s”—yes, he sometimes refers to it as if it is a friendly adversary—with the same competitive drive that fueled 6,656 big league plate appearances, 255 career homers, a career .352 on-base percentage and two World Series rings despite the fact that he played only one year of baseball at Michigan State.
“What I try to do is gather a team of guys together, talk to people all over,” he says of the doctors and specialists who are his new teammates. “There’s nothing out there you can unequivocally say will stop the progression, or cure it, right now. They’re close.”
He’s met with folks from the Michael J. Fox Foundation on more than one occasion, and he plans to attend their annual gala in New York in November. His mind hungers for information. His spirit still thirsts for competition.
Lea and Kerri learned that as soon as his therapy began in April.
“They were really, I don’t want to say in my face, but they realized what I expected to do,” Gibson says. “How I’ve approached all of my endeavors through life, I approached that. I took it as a challenge.
“But when I was being foolish, I felt like it was Sparky all over again. They were teaching me the fundamentals.”

EFK/Associated Press
Early in his baseball career, young and brash, Gibson clashed with Sparky Anderson, the legendary, old-school Tigers manager. Both men were competitive, stubborn and unrelenting, resulting in, as Gibson says, “some tough-ass times.”
By the end of their run together, highlighted by that ’84 title, they had reached a destination that neither had seen coming. In a frame in Gibson’s office today, there is a handwritten letter from the late manager sent when both men were older and wiser.
“It basically says, ‘I just want you to know, though you were a challenge, the memories that we made together were unforgettable,'” Gibson says. “And his favorite part of managing all those years were those type of memories where he built a relationship.”
Teamwork. Though Gibson initially came at things differently than Sparky, he ended up in the same place.
You bet those lessons learned on the baseball field and beyond are being employed in his current battle.
“My deal is, I want to find something not only for my benefit, but for everybody’s benefit,” Gibson says. “I want to try to make a difference. I see it the way you look at a successful team. There are certain components, and really the top component is that they’re pulling for each other, they want to succeed, and they don’t care who gets the credit. Right?”
Here, he tells a story about 1988, his iconic home run, the underdog Dodgers and him winning the National League MVP award while practically pulling his team by its throat to the NL West title.
“When I won the MVP, I lived north of here in the boondocks, and we probably had 60 media and friends there,” he says. “We had a little press conference and I hated it. It was all about me and the MVP, and I was talking about myself and I hated it.

Mike Powell/Getty Images
When we won the World Series, we had a parade both times. That’s over a million people. And that is fun, when you can influence that many people in a positive direction.
“When you think of the things you’ve done athletically, or the major things you’ve done in your life, what were the things that made you feel happy, like you’ve accomplished something? It’s when you’ve sacrificed for a cause.
“That’s kind of where I am now as far as getting involved in how to make people, first of all, know how to identify it, where to go, how to make it more efficient, how to make it cheaper and, most of all, find a cure.”
It is why he has decided to take this fight public, and why he gave his doctor the green light to talk for this story.
And he is doing it all in his own inimitable way.
“I call him the Rammer because his name is so f–ked up to say,” Gibson says of Sriram, grinning. “I told him, ‘Now you’re the Rammer. I’m not going to say your whole name anymore.'”
Over the telephone, the neurologist laughs. Hard.
“Yes,” Sriram says. “And by the way, no one else calls me that.”
When JoAnn walks upstairs for a bit to pack for a weekend getaway with a friend, Kirk lowers his voice. And, just for an instant, it catches with emotion.
“She’s been unreal,” he says. “She’s a rock. Sweeter than sweet. She is such a good person as a mother and leader of our family.”
Kirk and JoAnn have four grown children, Colleen, Kirk, Kevin and Cameron. It takes a lot to keep a baseball family together, and between them, Kirk’s mother (his father passed away several years ago) and JoAnn’s parents and siblings, there is even more heavy lifting when something as insidious as Parkinson’s comes calling.
“It’s been an interesting competition this summer,” Gibson says.
He returned to the Tigers television booth in July following the three-month absence that gave him a chance at therapy and to regain his balance.
No, you wouldn’t exactly wish for a summer like this. But that doesn’t mean it hasn’t been filled with some very special moments. Sometimes life calls a timeout so you can appreciate the little things. And you’re reminded, they’re not so little after all.

Photo courtesy of Kirk Gibson
Kirk and JoAnn spent a lot of the summer catching up with some of their favorite bands, among them Cheap Trick and guitarist Rick Nielsen.
So, without a manager’s job in the spring, there were family trips to watch son Kevin play hockey for Wisconsin-Stevens Point (jersey No. 23, of course). With extra time in April and May, Kirk and JoAnn saw several of Cam’s baseball games at Michigan State. And in Kirk’s words, they’ve had an “unreal concert season” seeing, among other acts, the Rolling Stones, Cheap Trick, the J. Geils Band, Kid Rock, Alice Cooper, the Foo Fighters, Brian Wilson, Rodriguez, Bob Seger and Van Halen.
In June, the Tigers drafted Cam, 21, in the fifth round, a moment that left his mother shedding tears of joy and his proud father video-recording the entire scene.

Photo courtesy of Kirk Gibson
Time away from the game allowed Kirk and JoAnn to watch his major league-bound son, Cameron, play at Michigan State.
“Give me a hug,” an ecstatic Cam demands of his father, walking straight toward the video camera. “Give me a damn hug!”
Oh, have there ever been hugs. Real and virtual. The outpouring of concern from family, friends and even those he barely knows in baseball has touched him in ways he didn’t know he could be touched. Among the texts he’s received, so many were unexpected, like this one from a St. Louis Cardinals outfielder:

Justin K. Aller/Getty Images
Hey Gibby, it’s Matt Holliday. I just wanted to pass along my admiration and support for you. I’ve always tried to play hard and tough like you did. I’m praying for your fight with Parkinson’s. With much respect and love, Matt.
The response Gibson sent Holliday:
Thanks for your kind words. It’s the only way to be. I’m going to kick ass and enjoy watching you.
“He’s battling,” Wells, the former pitcher and Gibson’s close friend, says. “He’s a tough son of a bitch. There’s nothing that man can’t conquer. He’s got a very strong mind, a very strong will.”

Andrew D. Bernstein/Getty Images
“He is in the best care, and he’ll have to be on the medication for the rest of his life,” says Alan Trammell, Gibson’s old Tigers teammate and another close friend. “The best compliment I can tell you is, he seems normal. It seems like he’s going to live a normal, productive life. He’s probably not out of the woods, but he seems fine.”
Academy Award-winning actor J.K. Simmons, a Michigan native, was a guest in the Tigers broadcast booth on Opening Day, and his was among the many other texts that poured in after Gibson’s announcement on April 28 with a statement he wrote himself. Because he wanted the public to hear it in his own voice.
“There are a lot of nice things that have happened,” JoAnn says. “We were walking around last week. We’ve lived here for a few years but we don’t know a lot of people here. A man, maybe our age, rode up on his bike while we were walking. He recognized Kirk and stopped for just a minute of local neighborhood chitty-chat stuff, and then he said ‘See ya’ and started pedaling away.
“And he got maybe half a house up and turned around and said, ‘I’m praying for you.’ And we didn’t even talk about that. He just felt like he wanted to get that in there.
“It was really cute.”
And in August, a couple of television analysts bumped into each other in a Comerica Park hallway when the Red Sox were playing in Detroit: Gibson and Eckersley.
“We had a great talk,” Gibson says. “There are things you want to make sure are right, and my thing was when people talk about that home run, I feel like sometimes they kind of overdo what I did and they undermine what Dennis did.”
That World Series night in 1988, Gibson was so hobbled by right hamstring and left knee injuries that he wasn’t even on the Dodger Stadium field for introductions before Game 1. He wasn’t supposed to play. But he sent word late to manager Tommy Lasorda that he had one at-bat in him, and up he stepped in the ninth with two out, a man on and the Dodgers trailing 4-3.
When Eckersley quickly threw two strikes, it looked like a mismatch. But Gibson battled to a full count and then, on the eighth pitch of the at-bat, remembering advance scout Mel Didier’s report that Eck liked to throw his backdoor slider in this situation, lightning struck. Gibson sent one of the most famous home runs in Dodgers history screaming through the evening into the right field pavilion, a game-winner that launched Los Angeles toward a thrilling upset.
“In a year that has been so improbable,” Vin Scully said so poetically on national television, “the impossible has happened!”
It was his only at-bat in that World Series.
Time passes and lives change. As the baseball drought continues in Los Angeles—the Dodgers have not played in a World Series since 1988—Gibson’s epic feat has grown to mythic proportions.
“That strong body,” Lasorda says. “That’s the thing you think about. God almighty.”
Eckersley was enshrined in the Baseball Hall of Fame in 2004. Lasorda, in 1997. Each will remain inextricably linked with Gibson’s force of nature willpower for as long as there is a World Series.
Gibson still owns a cassette tape of the Dodgers’ radio broadcast that night with the late Don Drysdale on the call. Sometimes, when he’s having a rough day, he still listens to it.
“You get embarrassed, because you want to be humble,” he says. “But at the same time, I’ll listen to that s–t any day. You know? It certainly doesn’t make me feel sad.
“You’ve got to lift yourself up. You’ve gotta do it.”
Right now, in that regard, he will use every weapon he has at his disposal. There is no telling what lies ahead, so he will do what he’s done for most of his life: lean on teammates like the Rammer and charge full speed ahead into the great unknown.
“One thing about Parkinson’s is, every patient is going to be different,” Sriram says. “Every person with Parkinson’s is like in their own little boats at their own speed.
“Kirk, even though he may have had the symptoms for a long time, he’s responded very well. I wouldn’t say he’s 100 percent, but he’s 90 percent better than when I met him in the clinic.”
Much as he loves his television work, Gibson absolutely would leap at the chance to climb back into a dugout, under the right circumstances, and help lead another group of young men to another set of unimagined heights.
“You know, I really miss the guys,” he says. “I mean, I have a bucket list, too. Would I like to win another World Series?
“Come on, I haven’t changed that much.”

Photo courtesy of Kirk Gibson
Kirk and JoAnn, pictured here in 1983, will celebrate their 30th wedding anniversary this December.
At the same time, this isn’t a man wired to just sit around. If that chance never comes, well, he’ll just move on to the next items on his list.
“You know what?” he says. “I can honestly say that whatever I do, I’m going to have a good time and do it right.
“Do I miss doing what I was doing? Yes. I loved it. The camaraderie. The challenges.
“Did I have a great year even though I was diagnosed with Parkinson’s? Yes. I did things I haven’t done in a long time. Enjoying friends. Creating new experiences. Spending time with my family.
“I’m not the kind of guy who is going to sit there and not go out and find something fun and rewarding to do. That’s just not my nature.”
Why, you might even say that in a year that has been so improbable, Kirk Gibson is hell-bent on winning another battle with what some might think is the impossible.
It is October, and time to sacrifice for another cause.
You bet there are more fist pumps ahead. And so much happiness, still, along the way.
As JoAnn says: “It was the summer of finding our new normal.
“And we found it.”

Improved Digestion and Better Health!

Please Check With Doctor First

We come up with all kinds of reasons why our stomachs feel upset or our digestion is out of whack.
But, come to find out, it could all be a matter of improper toilet seat positioning. We take it for granted that we are just supposed to plop right down on the circular porselin commode and do our business. But you could in fact be doing it all wrong.
How do you sit down while on the toilet? Probably like this, right?

Or maybe like this when you are really tired or really trying to go. But this is actually worse than the other position

There’s another position coined the 35-degree position which is much more natural and does not cut any flow or movement off at all. This is actually the normal position in many other cultures. It is only in the West that the other style, the 90-degree position, is considered normal. Nobody knows how or why this unnatural position developed.
So what can we Westerners do, short of trying to build a whole new custom toilet? The answer is pretty simple. Just implement a stool in your bathroom as this will provide your feet with enough rise to make bowel movements become much more natural.
When you realize that this indeed could improve digestion, then you can see how huge this could be. It’s amazing how other cultures already seem to understand this, yet we have always taken it for granted that our way is the most natural way, when clearly this isn’t the case!

Age at onset and Parkinson disease phenotype

Feb. 10, 2016

  1. Nicola Pavese, MD, PhD

50 year old

80 year old


Objective: To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD.
Methods: We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50–59 years, 60–69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers.
Results: Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF α-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups.
Conclusions: Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials.

William Damelio Launches a Specialized Speech Therapy Program for People With Parkinson's Disease

Published: Feb 12, 2016 

Speech therapy can help Parkinson's patients with problems such as soft or hoarse voice, mumbled or monotone speech, and swallowing difficulties that start early in the disease process and progressively diminish quality of life.

PALM BEACH, Fla., Feb. 12, 2016 /PRNewswire/ -- Many voice problems improve dramatically with the help of a speech language pathologist. Appropriate loudness, pitch and quality can be achieved with the assistance of speech language services.

Speech therapy can help Parkinson's patients with problems such as soft or hoarse voice, mumbled or monotone speech, and swallowing difficulties that start early in the disease process and progressively diminish quality of life.

The speech therapy method William Damelio uses is the Lee Silverman Voice Treatment (LSVT). LSVT is the "gold standard" in treating speech disorders in people who have Parkinson's disease and consists of an intense therapy that teaches patients to develop the strength required to speak at a normal vocal loudness. The strong theoretical and clinical research base behind LSVT has demonstrated substantive results including improved vocal loudness and intelligibility, improved ability to swallow, and increased facial expression.
Speech therapist William Damelio works with people who have difficulty talking or understanding language, difficulty swallowing, and with people who have cognitive, reading or writing disorders.  Evaluation services include the full range of speech and language disorders, clinical swallowing assessment and modified barium swallow.  His patients' diagnoses include stroke, head injury, head and neck cancer, laryngectomy, Parkinson's disease, ALS, MS, developmental disorders, and related disorders of communication and swallowing.  Home program is usually an integral part of the treatment plan.

Speech-language pathologists (SLPs) work to prevent, assess, diagnose, and treat speechlanguage, social communication, cognitive-communication, and swallowing disorders in children and adults.
William Damelio M.S., CF-SLP is licensed in the state of Florida as a speech and language pathologist and is a LSVT LOUD certified clinician. He holds a master's degree from Nova Southeastern University. Speech Therapist William Damelio evaluates and treats speech, voice, and swallowing disorders. William specializes is voice, swallow, cognitive, and fluency (stuttering) disorders. William Damelio CF-SLP also volunteers at Parkinson's disease support group sessions for the American Parkinson Disease Association (APDA) and the National Parkinson's Foundation of South Florida (NPF).
Name: William T. Damelio
West Palm Beach, FL
Ph: 914-563-9343

Friday, February 12, 2016

New Treatments, New Technologies in Parkinson Disease

Bret S. Stetka, MD
Disclosures | February 11, 2016

Editor's Note: 

Medscape recently spoke with Brian Fiske, PhD, senior vice president of research programs at the Michael J. Fox Foundation (MJFF), about the latest advances in the understanding and treatment of Parkinson disease (PD). 

Medscape: Welcome, Dr Fiske. The MJFF recently held its yearly research conference. What were some of the most promising highlights?
Dr Fiske: A lot of interesting work was discussed at this meeting. The goal was to highlight some of the areas that the MJFF has invested in and where we see really interesting promise. When we invite our grantees to present at this meeting, the goal is to try to build some of that excitement and interest in those project areas. Two talks during the session that focused on disease-modifying therapeutics were of particular interest.
One was from Dr Lars Wahlberg from NsGene; he was talking about his program around delivering the growth factor glial cell line-derived neurotrophic factor (GDNF) to people with PD, which is work he has been doing for quite some time now with us. The idea is packaging GDNF within what he's calling an "encapsulated cell" therapeutic approach; these encapsulated cells will secrete GDNF into the brain of people with PD, with the goal of protecting dopamine neurons.
It's an interesting idea. As a field, we've researched neurotrophic factors before, and there are a lot of challenges and problems that we've faced. I think what's interesting about this approach is that it's a novel twist on how to deliver a growth factor to the brain. He's really gearing up now for potential future human trials, and he's doing some additional work to try to better understand the capabilities of the system. It's really interesting to see the continued progress in that area.
Medscape: What has previous GDNF research in animal models of PD shown?
Dr Fiske: In general, the growth factor field has tried a couple of different approaches, including delivering both GDNF as well as another growth factor, called neurturin, in a variety of different ways. These include infusing the protein directly through a pump mechanism into the brain and also using something more novel, such as gene therapy.
Different companies have tried these approaches; unfortunately, the trial results to date have not been particularly positive, for a lot of reasons that people are still trying to figure out. In general, I think that there is still promise in neurotrophic factor therapeutics if we can do the trials correctly and safely, and in the right people.
Medscape: You described the mechanism as being cellular packets. Are these stem cells that release the growth factor?
Dr Fiske: These are engineered cells that Dr Wahlberg has basically created to produce GDNF. The technology here is that they're encapsulated in a way such that you could put them in the brain, but you could also remove them if you needed to—either for safety reasons or other reasons, to manipulate how you deliver them. It's like using the pump that infuses into the brain: If need be, you can turn off the pump. Gene therapy is obviously more of a permanent production, so if you put a gene into the brain, it will continue to produce GDNF. This was sort of a compromise between the two.
The encapsulation approach also helps to ensure that the cells are protected from possible immune rejection by the patient, which is obviously another important concern.
Medscape: So a neurosurgeon would place these packets in the substantia nigra or some other region of interest? 
Dr Fiske: Yes, and then it would produce GDNF, secreting it from these cells and acting as neurotrophic support for the brain.

Identifying Genetic Targets for Drug Development

Medscape: That's fascinating. What other research presented at the meeting shows particular promise, in your opinion? 
Dr Fiske: I think the other interesting highlight was around a genetic target for PD. There is a gene called leucine-rich repeat kinase 2 (LRRK2); in about 2004, some of the mutations within the gene were first discovered to be associated with PD. Since that time, people have really become excited about this target for a few reasons. One is because of the genetics; there is a strong genetic link to PD.
But also, the gene encodes for a type of protein called a kinase, and because of that, drug companies have become very interested in developing drugs that target it. They are very familiar with making drugs against kinases from other fields, such as oncology. Because of the really strong genetics and the compelling biological function of the protein, it's had a robust response from drug-makers working in the PD field.
What was interesting about the presentation at the conference—which was presented by one of our research staff members, Dr Marco Baptista—was a lot of work that we've been doing in the past year or so, looking at the potential safety of LRRK2-targeted targeted drugs. It started about a year or two ago, when some initial data came out showing that Genentech's version of an LRRK2 drug, when delivered into nonhuman primates, was showing some cellular abnormalities in lung tissue. We very quickly worked with them to try to verify that finding, to be sure that we could replicate it and understand it to determine whether it was really true or not. We've been working to verify those findings, first with Genentech and then ultimately with other companies.
Marco presented the outcomes of some of these studies, looking to demonstrate whether or not we can see this lung cellular abnormality in primates treated with LRRK2 inhibitors. We've also been trying to better understand what this could actually mean. For example, is it causing any functional changes in the lung, and are there detrimental effects? So far, we don't see any functional impact on the lung tissue at all, and the cellular abnormality is reversible when the drug is stopped, so our sense is that many companies will continue to pursue their LRRK2 inhibitor programs regardless of this potential finding. We'll need to decide in future clinical trials whether we need to put in particular safety measures to look for lung function changes in people.
Medscape: How far off do you think human trials of LRRK2 inhibitors are? 
Dr Fiske: It's hard to say. I think it really depends on a variety of factors. It's been relatively easy to make LRRK2 drugs because of the chemical knowledge people already have around this type of protein and drug target. I think the real challenges are more around the trials.
Obviously, if you're going to be moving into a clinical trial, presumably you're going to want to start first with people who carry the LRRK2 mutation. Making sure that we could actually find enough of those people, and at the right stage of PD, to actually be able to do this type of trial is one logistical challenge.
Another important issue is what types of biomarkers you would want to measure in these individuals, to know that your drug is actually affecting not only PD-relevant biology but also LRRK2-relevant biology specifically. I think we will see some of these drugs start moving into the clinic in the next couple of years, on the basis of our initial forecasting.

Using Biomarkers in Predictive Modeling for PD

Medscape: How about biomarkers? Was there anything new this year at the conference?
Dr Fiske: Yes, there was some interesting work around biomarkers. Obviously, this has been a big effort for the MJFF, and we've invested quite heavily in this area—in particular with regard to a large study, the Parkinson's Progression Markers Initiative (PPMI). Now that the study has been ongoing for 5 years, we're starting to get really meaningful data out of it.
One presentation that I think was particularly interesting was from Dr Andrew Singleton at the National Institute on Aging, which is part of the National Institutes of Health. He has been utilizing some of the data from PPMI, along with other data, to devise predictive models that could be used to help determine whether someone is at risk for PD. He's looking at a combination of genetics and some clinical features that basically allow you to distinguish people with PD from those without PD. The idea is that you ultimately predict whether someone might be at high risk for getting PD. These data were actually published in Lancet Neurology this year.[1]
A nice feature of the PPMI study is that the data that we collect are made available in real time, so people can have access to them as soon as we're able to get them out through the distribution mechanisms. People are then able to do these types of studies far more easily.

The Prion Hypothesis: An Update

Medscape: How about the idea that PD might be a prion-like disorder? Have there been any recent updates in the field here? 
Dr Fiske: This continues to be an interesting area. What's most exciting about alpha-synuclein in the therapeutic space right now is that we have multiple companies conducting clinical trials with various alpha-synuclein–based therapeutics: AFFiRiS, Prothena, Biogen, and Neuropore are developing therapeutic programs around alpha-synuclein in the clinic.
The prion hypothesis is very interesting, but whether it will necessarily affect existing therapeutic approaches is unclear. Most of these approaches are not targeting the actual mechanism of the alpha-synuclein spread, but rather trying to target alpha-synuclein directly and lower it or get rid of it. Hence, we don't think that answering the question about whether alpha-synuclein spreads in a prion-like mechanism is necessarily going to affect current therapy, but you never know.
Medscape: Do you think that the prion theory could be the unifying factor between PD and other neurodegenerative disorders, including Alzheimer disease?
Dr Fiske: I think it's an interesting question to ask. And I do think that the idea of an abnormal protein causing other proteins to become abnormal and spreading across the brain could potentially be a common thread underlying a number of neurodegenerative diseases. I think it is something that we continue to monitor very closely. Obviously, if that is true, it gives you some common areas and ways to target those kinds of mechanisms that could then have an impact beyond PD.
Generally, in the field of neurodegenerative research, people are starting to home in on these kinds of common biological pathways—how proteins are handled and distributed and gotten rid of in cells, and also how bioenergetic mitochondrial dysfunction might be involved. I think as we understand more about these diseases, we may start to realize that there might be more similarities than differences.
Medscape: Are there any final highlights from the research conference you'd like to share? 

New Formulations, New Technologies

Dr Fiske: Dr Warren Olanow from Mount Sinai Hospital discussed the plethora of options that are now coming to patients in terms of different ways to deliver dopamine therapeutics. In the past, it's always been just the traditional dopamine approaches (eg, Sinemet® [carbidopa/levodopa]), and then some of the dopamine agonist drugs that are available. We're now starting to see additional types of drugs becoming available, including intestinal gels (Duopa™) and extended-release formulations (Rytary™), for example.
Dr Ray Dorsey from the University of Rochester discussed another interesting area: the growing trend to use different technologies in PD care, in particular wearable devices and smartphones. We're investing in this area ourselves and trying to collect data in novel innovative ways from people with the disease, so that we can better understand their day-to-day experience. I think we will continue to see this type of movement in the field as we better understand the technologies we have, and what we do ultimately with the data they can supply.