Fall 2016
What’s in the Parkinson’s Medications Pipeline?
When will newer and better medications be available for people with Parkinson’s disease (PD)? How
will they help you or a loved one who lives with PD?
We cannot know these answers for sure, but we
can observe the possibilities by looking at the research
pipeline — the process by which researchers find and
test new treatments.
Currently, scientists
are focusing on two major
categories: therapies that
aim to ease the symptoms of PD, and those
that show promise to
slow or stop its progression. Treatments in both
categories are making their way through the pipeline.
While it is difficult to predict which ones will come to
market next, we can look at trends to see where we are
now and where we might be in the future.
The Drug Development Process
Scientists typically identify new medicines in
one of two ways. One is to test compounds that are
IN THIS ISSUE
2 | Letter from Leadership
3 | Solving PD Side Effects
4 | Cognitive Issues: Advice for
Parkinson’s Care Partners
9 | PD Take 3: How Can I Cope
with Pain in Parkinson’s?
10 | Join the Upcoming Series of
PDF PD ExpertBriefings
10 | PDF Champions in Action
11 | Meet the Team Helping to
#EndParkinsons
11 | PDF News & Events
already approved by the US Food and Drug Administration (FDA) for use in treating other diseases to see
whether they might also work for Parkinson’s disease.
The other is to theorize a new pathway that may be
applicable to Parkinson’s disease, and then to find a
compound that can be developed to target it.
Under both approaches, the therapy must travel
through a multi-step process before it can be approved
for the market, and reach the people who live with PD.
Basic/preclinical research. In this phase, scientists
look at the building blocks of PD (the brain, neurons
and chemical reactions) seeking clues to help us better understand the disease. They identify new compounds that have potential to treat PD, and test them
— first in simple PD models, such as cells in a Petri
dish; later, in more complex models, like yeast and fruit
flies; and then, in complex models, such as rats.
Clinical trials. Once a potential new drug has
been “validated” through animal testing, it may
move to the phase where it needs to be tested on
humans, called clinical trials. Clinical trials typically
>> Read more on page 6
proceed through four phases.
Science News |
Study Links Traumatic Brain Injury with Parkinson’s
A new study finds that a single traumatic brain injury from a blow to the head, with
loss of consciousness of more than an hour, may increase a person’s risk of developing Parkinson’s disease (PD) decades later. The results appear in the July 11 online
edition of JAMA Neurology. This topic has been in the news lately, given the widespread coverage of the death of boxing legend Muhammad Ali, and the concerns
about the neurological implications of repeated head injuries experienced by ath>> Read more on page 8
letes. This new study differs in that it looks at the effects of
Inhaled Levodopa Provides Relief for “Off” Periods
An experimental inhaled form of levodopa may help to rapidly relieve Parkinson’s
disease (PD) motor symptoms during “off” periods, the times when symptoms return
between regular doses of levodopa. The results appear in the April 19 online edition
of Movement Disorders. Carbidopa/levodopa, most often prescribed as Sinemet®, is
the most effective treatment for PD movement symptoms. But many people find that
as PD progresses, the effects of Sinemet wear off in between doses. Researchers led
by Peter A. LeWitt, M.D., M.M.Sc., at Wayne State University in >> Read more on page 8
www.pdf.org
Letter from Leadership
Dear Friends:
It was exactly 20 years ago when
Muhammad Ali, the best-known athlete in the world of his time, sounded
the gong at the opening of the
Olympic Games and startled millions
“[W]e have been
busy creating an
exciting transformation within
the Parkinson’s
community.”
Robin Elliott
of viewers with the Parkinson’s tremor
that was so evident in his posture. In
the years that followed, he did much
to give a poignant, brave human face
to Parkinson’s disease.
Since that moment, much progress has been made in the Parkinson’s community. In fact, because
of your support in particular, PDF
investments have helped to advance
research, care and patient advocacy.
Evidence of this can be seen on
pages 6 to 7, where our scientific team
reviews the drug pipeline, and on
page 11, where you can “meet” the
talented members of our team.
More recently, as some of you may
know, we have been busy creating
an exciting transformation within the
Parkinson’s community. Now the moment has come. In August, the Boards
of Directors of the Parkinson’s Disease
Foundation (PDF) and the National
Parkinson Foundation (NPF) announced
a signed agreement creating an historic
merger between the two organizations.
The new entity, which will be
known as the “Parkinson’s Foundation,” is expected to have an initial
Pre-order the
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annual budget of close to $20 million,
a professional staff of almost 100,
and — most importantly — a solid
commitment to taking on the two
most important challenges that face
our community: pursuing the cure for
Parkinson’s, and — for as long as this
eludes us — providing the care on
which the people who live with the disease, along with their families, depend.
It is a transformative moment and
we believe it will be a bright source
of new hope for the over 10 million
people worldwide who live with Parkinson’s disease.
If you have questions or suggestions as to how we might better serve
the community, I invite you to contact
me personally at (212) 923-4700 or
[email protected]. I and my colleagues
will do our best to answer them. And
if you are already a contributor to PDF,
or wish to become one, I hope the
news of this historic move will increase
your confidence in us and your support for our work.
Finally, a very personal note.
Muhammad’s dramatic TV appearance
in 1996 took place just a few weeks after I began my own tenure at the helm
of PDF. His public role and contributions to our community, through to his
death just a few months ago, bracket
the timeline of my own modest contributions almost exactly. My admiration
for what he was able to achieve both
reinforces my pride in what PDF (now
PF) has been able to do over these two
decades — and reminds me of how
much remains to be done.
PDF Advisory Council Reflects on
Muhammad Ali’s Impact on the Cause
In the weeks following Muhammad Ali’s
death, many in the Parkinson’s community
shared their reflections about his impact on
the cause. The following sentiments were
shared by members of the PDF People with
Parkinson’s Advisory Council.
Ali’s presence and optimism as a boxer were
second to none, and he carried that same
spirit over to his journey with Parkinson’s. He
lived every day as if it were his last, exemplifying his own admonition to ‘make the days
count.’ The Parkinson’s community mourns
the passing of a man who left us with this
legacy: to live well and make each day count,
while we search for the cure.
Daniel Novak, Ph.D., Fort Worth, TX, Chair
Ali’s efforts to raise awareness advanced
the cause for all of us. I hope that, as a
society, we take this opportunity to invest in
the research that will finally give Parkinson’s
disease the knockout blow that millions of us
worldwide so urgently need.
A.C. Woolnough, Sandpoint, ID, Vice Chair
Inspiration was ‘The Greatest’s’ greatest gift,
helping countless people living with Parkinson’s to overcome the depression, apathy and
anxiety that are the invisible symptoms of this
chronic, incurable disease. By living with the
disease for nearly half his life with dignity, humor and compassion, he showed us that when
it comes to Parkinson’s, fighters always win.
Jay Phillips and Marilyn Phillips, P.T., Summerville, SC
In the face of a glaring media spotlight and
a chronic, progressive neurological disease,
Ali made the absolute best out of Parkinson’s
and allowed the world to witness it. As a fellow person living with Parkinson’s, I’m grateful for how he motivated many others with
PD to live life to the fullest, and for the many
wonderful things he did to bring awareness
to the disease.
Alan B. Zimmerman, Knoxville, TN
Robin Anthony Elliott
CEO
2017 Creativity and Parkinson’s Calendar
Featuring the inspiring artwork of people living with PD.
(800) 457-6676 | www.pdf.org/creativity | [email protected]
2 | PARK IN SON ’S D IS E A S E F O U NDAT I O N
Share comments and
suggestions with the
Parkinson’s Disease
Foundation at 1359 Broadway,
Suite 1509, New York, NY 10018,
[email protected] or (800) 457-6676.
Spotlight on Research |
Solving PD Side Effects: Dr. Björklund Tests New Technology to Ease
Dyskinesia in Parkinson’s
Are you one of the many people who experience side effects from Parkinson’s disease (PD) medications? Among common side effects are the involuntary twisting and writhing movements called levodopa-induced dyskinesia (LID) that often
accompany long-term treatment with carbidopa/levodopa (Sinemet®). Luckily, Tomas Björklund, Ph.D., of Lund University in
Sweden, a scientist funded by the Parkinson’s Disease Foundation (PDF), is seeking solutions. In 2013, he was awarded a twoyear PDF research grant, which he used to explore cutting-edge technology to help us understand and ease dyskinesia in PD.
Q. Why did you choose to study LID in Parkinson’s?
A: For me, there are two major reasons. The first is
to help people with PD. Since we cannot prevent or
cure PD, we rely on levodopa as our best treatment.
While it can improve quality of life dramatically, it
also has flaws. If we could reduce or prevent LID, we
could have a real
impact on quality
“[W]e identified
possible drug
of life for many
targets that we
people. This is
believe may
a strong driving
silence serotonin
force behind our
neurons and ease
LID in PD.”
research. The
second reason is
Dr. Tomas Björklund
to understand the
brain and how it adapts to new situations, including
changes caused by Parkinson’s. Such knowledge may
help us understand how Parkinson’s develops.
Q. Can you summarize your research?
A: To understand the brain changes behind dyskinesia, we looked at three types of brain cells: dopamine
neurons (the kind lost in PD), acetylcholine neurons
and serotonin neurons. There are many challenges
to studying brain cells, but two new technologies
have helped us to overcome them. The first was the
development of an animal model: rats with PD symptoms that are very similar to humans. The second was
the development of chemogenetics, which allowed us
to use designer drugs/chemicals to turn geneticallymodified brain cells “on” or “off” like a light switch.
It took us nearly a year to make the technology work,
but when it did, we were able to study — more closely
than ever before — brain cells in a rat model of PD.
We studied the effects of the technology both in rats
that received levodopa and in rats that received cell
replacement, to understand LID in Parkinson’s.
Q. What did you learn about LID?
A: We discovered information about how the brain
works to cause dyskinesia. Our studies showed that
LID is caused in part by an imbalance in two types of
brain cells — dopamine and acetylcholine neurons.
We also found that a third type of brain cell — serotonin neurons — contribute to this imbalance. Lastly,
we identified possible drug targets that we believe
may silence serotonin neurons and ease LID in PD.
Q. What is your plan for advancing this research?
A: The next step is to move this research closer to
the clinic. Making discoveries in animals is an important first step in research, but turning that knowledge
into drugs that can help people is a far more daunting
task. The good news is that there are already drugs
similar to the ones we have identified in development.
But right now, they are being tested for diseases
other than PD. Our team has begun discussions with
the pharmaceutical industry about the possibility of
testing the drugs in PD. A second goal is to develop
a “designer drug” technology, similar to the one used
in rats, for people. This is not an easy task, but we
think that we are on the right track.
Q. Is there anything else you’d like readers to
know about this work?
A: First, I would like to direct a big thank-you to all
the people who have supported PDF and thereby,
indirectly, our work. It is easy to think that a small
contribution isn’t that important, but it is! The sum of
this support can make all the difference for enabling
a radically new idea to be tested. In my case as a
young group leader, it was very tough to get support
for my high-risk projects, but the PDF grant made it
possible. I hope that PDF can continue to provide
this crucial support to others in the future.
FA LL 2 016 PD F NE WS & REVIEW | 3
Cognitive Issues: Advice for Parkinson’s Care Partners
By Rebecca Gilbert, M.D., Ph.D.
Are you the care partner of a person who lives with
Parkinson’s disease (PD)? Many care partners report that
the cognitive changes that can develop with Parkinson’s
disease are among the most worrisome of PD symptoms.
How can you and your loved one cope with these symptoms? Here are some tips.
“[A]ll of us can benefit from a simple
strategy: get enough rest, learn new
things, exercise, do one thing at a
time, focus on what you can do, maintain a social life and keep busy.”
Rebecca Gilbert, M.D., Ph.D.
Overview
Over the course of PD, most people experience
some degree of cognitive change. The brain changes
that underlie the disease can affect a person’s ability to
multi-task, to pay attention and to think quickly. Common
symptoms include feeling distracted, and having trouble
with solving problems, planning and recalling information.
Some people may develop more serious challenges, such
as dementia. Like any other symptom of PD, the experience will vary from person to person. Some people will
notice changes at the time of diagnosis, while others will
not experience them until years down the road. For many
people, symptoms fluctuate from one day to the next, or
from one hour of the day to another.
Causes and Imitators
A person’s cognitive abilities can be affected by a
variety of factors, including medications and the presence
of health issues other than PD. Care partners play a key
role in identifying these other issues, and bringing them
to the attention of the neurologist.
Medical Conditions. We know that imbalances in
thyroid hormones and deficiencies in vitamin B12 can affect thinking and cognition. Your primary care doctor can
rule these out with blood tests, and treat them if needed.
In addition, some illnesses and infections — for example,
urinary tract infections and pneumonia — may cause sudden cognitive changes. Remember that in PD, cognitive
changes happen slowly over time. If changes are sudden,
ensure your loved one sees a doctor as soon as possible.
Medications. Some medications can cause cognitive
issues. For example, those prescribed early in PD may
cause cognitive issues later. These include drugs with an-
4 | PARK IN SON ’S D IS E A S E F O U NDAT I O N
ticholinergic properties, such as PD medications including
benztropine mesylate (Cogentin®) or trihexyphenidyl (Artane®) and others that are used to treat urinary frequency
and urgency, depression and allergies. Other medications that can impair cognition include steroids, narcotics
for pain, and benzodiazepines used to treat anxiety and
sleep, including lorazepam (Ativan®), diazepam (Valium®)
and alprazolam (Xanax®). If your loved one with PD is
experiencing cognitive changes, bring a list of all medications to the neurologist to discuss adjustments.
Sleep Issues. We know that being well-rested is the
foundation for feeling mentally sharp. But most people with PD have trouble getting a good night’s sleep.
Causes include sleep apnea, a disorder in which breathing stops and starts during sleep; restless leg syndrome
(RLS), which may interfere with sleep; and REM sleep behavior disorder, during which people act out their dreams,
sometimes violently. In addition, PD itself and some PD
medications can cause daytime sleepiness.
If you have trouble going to sleep at night, or you find
yourself waking up frequently, talk to your neurologist.
Sleep problems can be treated with melatonin or other
sleep aids. Sleep apnea can be helped with a device
called a CPAP (continuous positive airway pressure). RLS
may be treated with medications such as dopamine
agonists, opioids and gabapentin, while REM sleep behavior disorder can be treated with the drug clonazepam
(Klonopin®). If getting better sleep does not help you stay
awake during the day, your doctor may prescribe a stimulant such as modafinil (Provigil®) or armodafinil (Nuvigil®).
Low Blood Pressure. Many people with PD experience a sharp drop in blood pressure when they stand up,
a condition that is known as neurogenic orthostatic hypotension. This not only causes lightheadedness; it also can
affect cognition. Be sure to drink enough water, and consider using pressure stockings or an abdominal binder (a
medical version of a girdle, available in drugstores). Also,
try raising your head slowly while getting up. In addition,
your doctor may prescribe a medication such as an alpha
agonist, fludrocortisone or droxidopa (Northera®).
Apathy and Depression. Care partners sometimes
say that they cannot tell whether an instance of their loved
one not accomplishing a task is a matter of inability or
lack of will. Keep in mind that apathy — that is, the loss
of interest in life — is a very common symptom of PD.
And depression, which is also common, affecting up to
60 percent of people with PD, may exacerbate or mimic
cognitive changes. Again, discuss these with the neurologist, who may suggest an antidepressant to help.
Caring in Parkinson’s |
Tips for Care Partners
• Focus on your partner’s abilities
Memory Boosters for People
with Parkinson’s
• If you find that you are becoming frustrated, take
time for yourself
• Write down appointments and events while
repeating each item out loud
• Do activities with your partner that you both enjoy
• Join a care partner support group
• Make to-do lists, then cross off each item as it
is accomplished
• Seek help for yourself — for example, counseling
or financial planning
• Set aside particular places for keeping keys,
wallet and other items
• Ask for help from your support network
• Avoid multi-tasking
Hallucinations in PD. Many people who take carbidopa/levodopa (Sinemet®) for PD motor symptoms experience visual hallucinations as a side effect. These are not
necessarily a sign of cognitive decline. Talk to your loved
one’s neurologist about possible medication adjustments.
Treating Cognitive Difficulties
If you have ruled out or treated these other causes,
and the person with Parkinson’s continues to experience
cognitive issues that are related to PD, what can you do?
Exercise. Many studies have shown that when
people with PD exercise, their scores on tests of attention and working memory improve. Clinical studies have
shown that exercises for stretching, balance and building
strength with weights are all effective. Encourage your
partner to do whatever exercise it is that he or she enjoys.
Train the Brain. Researchers are studying cognitive rehabilitation programs for PD, to improve memory,
attention and executive function. Right now, these
programs are unavailable outside of clinical trials, but occupational therapists offer similar tools. In the meantime,
encourage a loved one to keep cognitively fit by learning
new things, engaging socially and staying busy.
Medical Therapies. One medication — rivastigmine
(Exelon®) — has been approved to treat cognitive issues
(dementia) specifically in PD. Other medications used in
PD but approved for cognitive decline in other conditions
include memantine (Namenda®). Clinical trials are studying new drugs (e.g., one called SYN120) for their potential.
Coping Skills for Care Partners
Care partners whose loved ones are experiencing
cognitive changes often wonder, how much should I push
my partner? For example, if my partner has difficulty using the cell phone, should I simply place the call for him?
Or should I insist that my partner “use it or lose it” when it
comes to tasks that require attention or planning?
No single answer fits every situation. Consider
whether the person with PD is becoming frustrated or
anxious. If so, an offer of help may be welcome. If the
person wants to accomplish a task on his or her own, try
breaking it down into a series of steps.
Care partners often ask what to do when a loved one
with PD is unaware of cognitive issues. Again, there is no
one-size-fits-all solution. Keep in mind that the person
may be aware of the changes, but may deny them, in order to maintain a sense of self. This can be a good thing
if it motivates him or her to stay active. But cognitive
changes need to be discussed if your loved one wants to
do something that poses a safety risk, such as driving.
Lastly, how can you cope, both individually and as a
team? Find support, whether it is in the form of friends,
support groups or counseling (see box above). Focus on
what your partner can do, whether it is dancing or watching a movie, and do it together.
Conclusions
When it comes to staying mentally sharp, all of us
can benefit from a simple strategy for maintaining mental
and physical health: get enough rest, learn new things,
exercise, do one thing at a time, focus on what you
can do, maintain a social life and keep busy. If this isn’t
enough, visit the neurologist with your loved one with PD
to discuss possible medical treatment. Care partners can
also help their loved ones to stay physically, mentally and
socially active at home. Finally, care partners need to take
time to care for themselves — both for their own health,
and to provide the best care for their loved ones.
Dr. Gilbert is Clinical Associate Professor of Neurology,
Marlene and Paolo Fresco Institute for Parkinson’s and
Movement Disorders at NYU Langone Medical Center.
FA LL 2 016 PD F NE WS & REVIEW | 5
What’s in the Parkinson’s Pipeline? | Continued from page 1
• Phase I: A drug is tested in 10 to 30 people for safety.
• Phase II: A drug is tested in a group of 50 to 150 people
for safety and efficacy in treating PD.
• Phase III: A drug is tested, typically in a group of 300
people (but as many as 3,000) at multiple locations. This
is the definitive study which determines whether a drug
is both safe and effective — and therefore deserves
FDA approval — or whether it falls by the wayside.
• Phase IV: A drug, after it has been approved, may be
monitored in a “post-market” trial to find out more
about how it works or if it has additional uses.
Recent Successes & Disappointments
In less than two years, three new PD therapies have
emerged from the pipeline and received FDA approval.
Two provide new ways to deliver carbidopa/levodopa, the
gold standard medication for PD, while a third addresses
symptoms of Parkinson’s disease psychosis.
• Carbidopa/Levodopa Extended-release Capsules
(Rytary™). This extended-release formulation of carbidopa/levodopa aims to reduce “off” time for people who experience this difficulty when taking other
levodopa-based PD therapy.
• Carbidopa/Levodopa Enteral Suspension (Duopa™).
This gel form of the drug is pumped directly into the
intestines to provide continuous therapy and avoid
wearing-off. It requires the surgical placement, in the
stomach, of a tube through which the drug is delivered.
• Pimavanserin (Nuplazid™). This is the first drug to be
approved for treatment of PD-related symptoms of
psychosis, such as hallucinations and delusions.
In addition to the approval of new Parkinson’s treatments, we have seen the approval of new uses for an
existing treatment. Deep brain stimulation (DBS) surgery,
which was originally approved for advanced PD in 2002,
has now been approved for earlier stages of Parkinson’s
BASIC
RESEARCH
DRUG
DISCOVERY
PREDISCOVERY
disease. The surgery is available to people who have
lived with PD for at least four years, and who are experiencing either (i) recent onset of motor complications, or
(ii) motor complications for a longer duration that have
not been adequately controlled by medications.
By contrast, take a look at the following medications.
What do they have in common? The answer is that each
of them showed promise in the early stages of research,
but in later-stage trials, were shown to be ineffective.
• AFQ056
• Creatine
• Cere-120
• Preladenant
• Cogane
• PYM50028
• Coenzyme Q10
• Ubiquinone
It is disappointing that these drugs didn’t prove effective in treating PD, but it is important to know that the
work done to test them is helping to inform new research.
Pipeline Trends: Therapies to Watch
After a drug has been shown to be safe and effective
in a phase III clinical trial, its sponsors must submit a New
Drug Application (NDA) to the FDA. If the FDA approves
the application, the drug can be marketed and sold in the
US. Right now there is one NDA pending review by the
FDA. Look for news about this drug soon.
• Safinamide (Xadago®). An add-on drug taken with levodopa to extend “on” time. It is approved in Europe.
Pipeline Trends: Therapeutic Agents
Currently, there are many therapies on the market
that help to ease the movement symptoms of Parkinson’s
disease. In the therapeutic pipeline (see page 7, top of
page), scientists are testing new medications and new formulations of existing medications to help better control
Parkinson’s movement symptoms, lessen side effects, or
treat symptoms for which effective medications do not exist (e.g., cognitive issues).
FDA
REVIEW
CLINICAL TRIALS
PHASE I
PHASE II
PHASE III
POST-APPROVAL
RESEARCH &
MONITORING
PHASE IV
1 FDAAPPROVED
MEDICINE
PIPELINE OF POTENTIAL NEW MEDICINES
6 | PARK IN SON ’S D IS E A S E F O U NDAT I O N
Research |
For example, most people with Parkinson’s are
familiar with carbidopa/levodopa, the gold-standard
medication for PD that is often prescribed as Sinemet®.
Sinemet affects the dopamine system in the brain. Two
therapies in the pipeline test new ways of taking the drug
(for example, with an inhaler) with the goal of overcoming
challenges like “wearing off.”
Meanwhile, a new class of Parkinson’s drugs called
A2A antagonists have been working their way through
the pipeline as well. Unlike other PD drugs, A2A antagonists do not affect the dopamine system. Thus, many
in the Parkinson’s community are hoping the drugs may
help to improve PD symptoms and enhance the effects of
levodopa, without worsening dyskinesia.
In the Pipeline: Therapeutic Agents
Phase I
• AAV2-hAADC. A gene therapy that works by allowing cells
in the body other than neurons to process levodopa.
• Donepezil (Aricept®). An Alzheimer’s therapy being tested
for dementia and mild cognitive impairment in PD.
• IPX203. An updated formulation of Rytary™, this
intermediate-release formulation of carbidopa/levodopa is
intended to improve upon the existing drug.
• OXB-102. A gene therapy that modifies neurons so that
they produce dopamine.
• ODM-104. A COMT inhibitor that enhances the effects of
levodopa by blocking the COMT enzyme.
Phase II
• PF-06649751. A dopamine agonist designed to offer fewer
side effects than currently-approved drugs in the class.
• SYN120. A new class of combination drug (dual antagonist
of the 5-HT6 and 5-HT2A receptors) being tested for treatment of cognition and psychosis in PD.
Phase III
• APL-130277. A new formulation of an existing PD drug,
apomorphine, that is placed under the tongue for rescue
from “off” periods in PD.
• CVT-301. An inhaled form of levodopa used as a rescue for
“off” periods.
• Istradefylline. An A2A receptor antagonist, already approved in Japan, that is designed to reduce “off” time and
suppress dyskinesias.
• NDO612H. A formulation of levodopa delivered through a
subcutaneous pump (needle placed just under the skin) to
even out symptom fluctuations.
• Tozadenant. An A2A receptor antagonist designed to
reduce “off” time and suppress dyskinesias.
• Vercise Primary Cell (PC) Deep Brain Stimulation system. A
new DBS surgery technology that aims to reduce side effects.
Phase IV
• Rivastigmine tartrate (Exelon®). The only medication approved by the FDA to treat dementia in PD; it is now being
tested for its potential to treat mild cognitive impairment.
In addition, gene therapies for PD continue to be
tested. In this type of treatment, a harmless virus carries
new genes into the brain cells affected by PD to either
promote dopamine production (to help treat symptoms)
or boost levels of substances that protect brain cells (to
potentially stop the disease).
Another approach to finding more effective Parkinson’s
therapies is finding ways to improve deep brain stimulation surgery. Researchers are testing DBS devices that may
better focus electrical stimulation on specific points in the
brain, or target new areas of the brain altogether. The goals
of these approaches are to reduce side effects and address
symptoms like gait and balance difficulties.
Pipeline Trends: Neuroprotective Compounds
People with Parkinson’s know all too well that we
urgently need therapies that can slow or halt disease progression. Although to date, none have been proven to
do this, some new approaches are working their way into
early clinical studies (see box at right, bottom of page).
Several of the potentially neuroprotective compounds in the PD pipeline focus on alpha-synuclein,
the protein that forms toxic clumps in the brain cells of
people with PD. Potential therapies would harness the
immune system to clear alpha-synuclein or use vaccines
to prevent or halt alpha-synuclein build-up. In addition, a
few others — for example, isradipine — have been used
for years to treat other health conditions.
A Look Ahead
It is difficult to predict which potential therapies will
work and which will not. For every potential therapy
that enters the process, one in a thousand will end up
being approved for PD. While we can’t know exactly
what’s next, we can be optimistic at the level and type
of research ongoing for Parkinson’s, all of which aims to
improve and more importantly, reverse the course of Parkinson’s for all of those living with the disease.
In the Pipeline: Neuroprotective Agents
Phase I
• AAV2-GDNF. A gene therapy treatment designed to boost
levels of GDNF, a naturally occurring protein that may
protect dopamine neurons in the brain.
• BIIB054. An immunotherapy that clears alpha-synuclein, a
protein whose build-up is thought to contribute to PD.
• NPT200-11. A drug designed to stabilize the brain protein
alpha-synuclein, whose misfolding is related to PD.
• PRX002. An immunotherapy that clears alpha-synuclein, a
protein whose build-up is thought to contribute to PD.
Phase II
• Nilotinib (Tasigna®). A drug approved for treatment of
blood cancers being tested for efficacy and safety due to
possible serious side effects.
Phase III
• EGCG. A compound found in green tea that works by
stopping alpha-synuclein clumps from forming in the brain.
• Isradipine (Prescal®). A calcium channel blocker that is approved for treatment of high blood pressure.
• Inosine. A nutritional supplement that converts to urate,
a natural antioxidant found in the body. A phase III trial
recently completed enrollment.
Phase IV
• None.
FA LL 2 016 PD F NE WS & REVIEW | 7
Science News |
Brain Injury and Parkinson’s* | Continued from page 1
single head injuries among older people who are more
representative of the general population. Researchers
led by Paul K. Crane, M.D., M.P.H., at the University of
Washington in Seattle, analyzed self-reported data, collected between 1994 and 2014, from 7,130 people who
had enrolled in various studies of memory, cognition and
aging. Study participants were 80 years old, on average, at
the time of the report and did not have dementia, Parkinson’s disease or Alzheimer’s disease (AD) at the time they
enrolled. Brain tissue was examined on autopsy for 1,589
participants, for signs of PD and AD.
Results
• A total of 117 new cases of PD were diagnosed.
• Among all participants, 865 reported having experienced a traumatic brain injury with loss of consciousness
at some point in their lives. A previous traumatic brain
injury with loss of consciousness of longer than one
hour, even decades earlier, was associated with three
and a half times increased risk of developing PD.
Inhaled Levodopa* | Continued from page 1
West Bloomfield, MI, tested a new inhaled formulation of
levodopa (CVT-301) to see if it would help to ease debilitating “off” episodes. The scientists recruited 86 people
with PD who reported experiencing at least two hours of
“off” time per day. On average, they were 62 years old
and had been taking levodopa for about eight years. For
four weeks, half of the participants used a special inhaler
to take CVT-301 when they experienced “off” periods, and
the other half took a placebo. All continued taking oral
levodopa. Participants were not informed as to whether
they were taking the drug or the placebo.
Results
• Participants used their inhalers, on average, twice a day.
• Participants who took inhaled levodopa, compared with
those who took placebo, showed significant improvement in motor symptoms — for example, their “off”
• A person’s history of traumatic brain injury was associated with accumulation of Lewy bodies in brain cells, the
hallmark of Parkinson’s disease.
• Microinfarcts — the microscopic strokes in the brain that
may cause dementia — were found more often than
average in the brains of people who had experienced
traumatic brain injury accompanied by loss of consciousness of more than one hour.
What Does It Mean?
Previous research has linked head injuries to neurodegenerative disease. This study illustrates a more specific
finding: that a single blow to the head causing a loss of
consciousness for more than an hour, even if it happened
long ago, may lead to a three-fold increased risk of PD
decades later. Although the vast majority of people who
experience head injury will not develop PD, this research
underscores the importance of preventing head injuries in
general. It also suggests that further research to explore
the connection between brain injury and Parkinson’s disease could be used to help reduce PD risk.
periods were shorter by almost one hour.
• Inhaled levodopa took effect within 10 minutes and
lasted for longer than 60 minutes.
• The inhaled levodopa did not cause dyskinesias, the
involuntary movements that can happen at the time that
oral levodopa is having its peak effect.
• While experiencing PD symptoms, participants were
able to prepare and take the drug themselves.
• CVT-301 generally was well tolerated, but some participants experienced dizziness, coughs and nausea.
What Does It Mean?
“Off” periods can be disabling, and currently, there are
very few options for coping with them. In this context, the
results of this small, early study are encouraging. Additional research, involving larger groups of study participants,
is underway, and the results will need to be evaluated critically before CVT-301 can be considered for FDA approval.
More Science News on PDF.org
• Parkinson’s Biomarker
Detected in Urine
• New Gene Discovered That
Causes Inherited PD
* To read the full summaries of these two stories, visit www.pdf.org/science_news.
8 | PARK IN SON ’S D IS E A S E F O U NDAT I O N
www.pdf.org/science_news
Understanding Parkinson’s |
3
PD Take
Tips & Tools from the PD Team:
How Can I Cope with Pain in Parkinson’s?
The Movement Disorders Specialist
Pain is a common symptom of Parkinson’s, yet it often goes unrecognized
by people living with the disease, their families and health professionals.
Keep a Pain Diary. Write down such events as when you take medications, when you experience the pain,
where it is located (neck, shoulder, foot, etc.), how long it lasts and any intervention that makes it better or
worse. Is the pain dull and achy, or is it sharp and stinging? Does it happen in the morning or when medications wear off? Share the diary with your doctor to help you both better understand and manage your pain.
Jori Fleisher, M.D., M.S.C.E.,
Assistant Professor of
Neurology and Population Health, Marlene and
Paolo Fresco Institute for
Parkinson’s and Movement Disorders at NYU
Langone, New York, NY.
The Physiatrist
Talk to Your Doctor. Ask your movement disorder specialist if pain might be due to PD-related rigidity. People with PD often experience shoulder tightness and pain, and may resort to injections and surgeries before
realizing it’s related to PD. Yet the PD-related rigidity that causes “frozen shoulder” often improves with medication, physical therapy and exercise … no scalpel needed!
Stay Active. This may seem counterintuitive to a person who is experiencing PD-related pain, but physical
therapy and exercise can be a big help. Research shows that people who are active rate pain as less severe and
less bothersome than people who are not. Try gentle exercises such as yoga, tai chi, stretching or swimming.
Pain can have a significant impact on quality of life for a person with Parkinson’s. If you
experience pain, make sure your health care team is aware of it.
Ask Your Doctor if Your Medications Should be Adjusted. Pain can occur in PD as a non-motor “off”
symptom, meaning that it fluctuates with the schedule of your PD medications. If this is a problem for you, it
may help to adjust those medications. Pain can also be aggravated by under-treatment of PD motor symptoms
(e.g., rigidity) or as a consequence of severe dyskinesia, a common side effect of PD medications.
Heather Baer, M.D., Associate Professor, Physical
Rehabilitation Medicine
and Neurology, University of Colorado School
of Medicine, Denver, CO.
The Psychologist
Maintain Your Exercise Schedule. Studies show that exercise can help with pain management for various reasons, including the release of natural opioids in the body. There is also some evidence to support the idea that
exercise may help people with Parkinson’s because of its likely effect on the brain’s pain-reducing pathways.
Consider Consulting a Pain Psychologist. Psychotherapy has been shown to be beneficial in managing pain.
Not only that, it’s also helpful in treating depression. Since depression is known to weaken tolerance for pain,
addressing it may help in the overall treatment of PD-related pain.
It is now well understood that the overwhelming majority of people who live with Parkinson’s experience disabling non-motor symptoms, such as acute and chronic pain.
Chart Your Course. Like Dr. Fleisher, I recommend that my patients keep a diary for as long as two weeks. Use
it to record the impact of stress, and of negative feelings (e.g., anger, depression and anxiety) on pain. Identify
the experiences that trigger your pain at its worst, to help you find ways of getting it under control.
Roseanne D. Dobkin,
Ph.D., Associate Professor
of Psychiatry, Rutgers,
The State University of
New Jersey, Robert Wood
Johnson Medical School,
Piscataway, NJ.
Stop Pain in Its Tracks. Develop a list of “go-to” coping strategies (e.g., listening to music, meditating, finding
distractions) and try using them at the very first sign of pain. It is much easier to control pain when it is in its
early, mild stages than to wait until it becomes severe.
Try to Put Pain in Its Place. Living with pain is not easy. But focusing on it intently may make it even worse. If
you notice negative thoughts, think of all you can do — for example, “I don’t like this, but I can stand it!” or,
“Here are strategies that I can use to manage it and live well.”
FA LL 2 016 PD F NE WS & REVIEW | 9
PDF News & Events |
Join the Upcoming Series of PDF PD ExpertBriefings
Find practical tips for taking charge of PD. Available online or by phone.
Getting Around: Transportation
and Travel with PD
Tuesday, September 13
Sara Riggare, Ph.D. Candidate, Karolinska
University and Rebecca Gilbert, M.D., Ph.D.
NYU Langone Medical Center
Parkinson’s Disease: Financial, Legal and
Medical Planning Tips for Care Partners
Diagnosis PD, Now What? Managing
the First Few Years with Parkinson’s
Tuesday, March 7, 2017
Suketu Khandhar, M.D.
Kaiser Permanente Sacramento
Medical Center
Is It Related to PD? Runny Noses, Skin
Changes and Overlooked PD Symptoms
In recognition of National Family Caregivers Month
Tuesday, November 8
Martin M. Shenkman, C.P.A., M.B.A., J.D.
Shenkman Law
In recognition of Parkinson’s Awareness Month
Tuesday, April 18, 2017
W. Lawrence Severt, M.D., Ph.D.
Mount Sinai Beth Israel Medical Center
Pain in Parkinson’s Disease
Tuesday, January 10, 2017
Jori E. Fleisher, M.D., M.S.C.E.
NYU Langone Medical Center
Sleep and Parkinson’s
Tuesday, June 13, 2017
Aleksandar Videnovic, M.D., M.Sc.
Harvard Medical School and
Massachusetts General Hospital
Each PD ExpertBriefing takes place LIVE online from 1:00 - 2:00 PM ET and then becomes a recording on PDF’s website.
Pre-registration is recommended; phone participants can access each LIVE seminar by dialing (888) 272-8710 and when prompted, entering code 6323567#. CEUs are available for some professionals via PDF’s sponsorship of the American Society on Aging.
This series has been made possible by educational grants from AbbVie, Inc. and Lundbeck LLC.
www.pdf.org/parkinsononline
WHAT’S YOUR PASSION?
See how PDF Champions are putting their passion to work for PD.
From left to right: On August 2, Rachel Isenberg raised nearly $5,000 through her Maclaren Glacier hiking-kayaking expedition in Alaska. On July 29 and 30, Bernadette
Lindquist hosted a garage sale for PDF in Reynoldsburg, OH, in honor of her husband, raising over $850. From July 28 through August 2, Jamie Malam’s 514-mile Cycle
for a Cure from San Francisco to Huntington Beach, CA, raised more than $2,000 for PDF. In late July, Stanley Fenn of Idaho Falls, ID, raised nearly $1,500 by flying his
plane across the Western US in Going to the Sky for Parkinson’s. On July 17, A.C. Woolnough and his grandson Nathan kayaked 50 miles around Lake Pend Oreille, ID,
to raise $700 in Paddle for Parkinson’s. On May 14, the NJROTC at Colts Neck High School in NJ raised $3,411 at their second annual Chase the Rainbow 5k Color Run.
Would you like to join our Champions? Contact us today. Our team will provide you with guidance and support.
@PDFChampions | www.pdf.org/champions
10 | PAR K IN SON ’S D I S E A S E F O U NDAT I O N
PDF News & Events |
Meet the PDF Team Helping to #EndParkinsons
PDF’s strategy for ending Parkinson’s is to build a team of leaders in research, health care and the patient community,
and then mobilize them to work together toward the cure. Meet members of the PDF team helping to #EndParkinsons.
Meet our research leaders. In July, PDF announced $4 million in research investments. Awardees include, left to right: Ignacio Fernandez Mata, Ph.D., of the
University of Washington (with his son) and James Dahlman, Ph.D., of the Georgia Institute of Technology, both recipients of Stanley Fahn Junior Faculty Awards;
Rosalind Roberts, D.Phil., of McGill University, a PDF Postdoctoral Research Fellow; and Emily Ong, of Lake Forest College, a PDF-APDA Summer Student Fellow.
Meet our health leaders. This summer, PDF held three trainings for The Edmond J. Safra Visiting Nurse Faculty Program at PDF and a pilot training for the
Physical Therapy Faculty Program at PDF. Our new nurse and physical therapy Scholars trained (left to right) at UCSF Medical Center, Park Nicollet Struthers PD
Center and Boston Medical Center. At far right, PDF Advocate Cindy Bittker spoke to the professionals who trained in Boston, MA, about life with Parkinson’s.
Meet our newest patient leaders. In July, PDF welcomed 20 people with PD and care partners to our advocacy network. They join 325 patient leaders who are
helping PDF to end PD. Pictured left to right are: the new PDF Research Advocates and faculty; Kirk Hall, M.B.A., of Denver, CO, faculty and veteran PDF Research
Advocate, and Benzi Kluger, M.D., of Denver, CO, faculty; and Sharlene Young of Chicago, IL and Jackie Robinson of Bellwood, IL, both new Research Advocates.
Community Events |
November
Moving Day® Miami
Date: Sunday, November 13
Place: Museum Park, Miami, FL
www.movingdaymiami.org
14th Annual Music for Parkinson’s
Wines on the Bay
www.pdf.org/music
www.winesonthebay.org
Date: Sunday, November 13
Place: Congregation Emanu-El,
Rye, NY
Date: Wednesday, November 30
Place: Coral Reef Yacht Club,
Coconut Grove, FL
Find more events or list yours on our website: www.pdf.org/event_calendar
Photo Credits: Page 10, photo six (Credit: The Journal); Page 11, row two, photo two (Credit: Boston Medical Center); Page 11, row three, photos one,
two, three and four (Credit: Chris Jorda Photography).
FA LL 2 016 PD F NE W S & REVIEW | 11
Fall 2016
1359 Broadway, Suite 1509 | New York, NY 10018
November is National Family Caregivers Month
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| [email protected]
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Disclaimer If you have or believe you have Parkinson’s disease, then promptly consult a physician and
follow your physician’s advice. This publication is not
a substitute for a physician’s diagnosis of Parkinson’s
disease or for a physician’s prescription of drugs,
treatment or operations for Parkinson’s disease.
©2016 Parkinson’s Disease Foundation
Board of Directors
John Kozyak, Esq., Chair
Howard Morgan, Vice Chair
People with Parkinson’s
Advisory Council
CEO
Julio Angulo, Ph.D.
Scientific Editor
Robin Anthony Elliott
Stephen Ackerman, Assistant Treasurer
Mary Bendelow, Ph.D.
Andrew Albert, Chair, Nominating and
Governance Committee
Elaine Casavant, R.N.
Carol Fox
Editor
Constance Woodruff Atwell, Ph.D., Interim
Chair, Scientific Advisory Committee
Anthony Geraci, M.D.
Christiana M. Evers
J. Gordon Beckham, Jr.
Andrée Jannette
Rebecca Miller, Ph.D.
Managing Editor
Marshall Burack, Esq., Assistant Secretary
Karen Elizabeth Burke, M.D., Ph.D.
Alessandro Di Rocco, M.D.
Alberto Dosal, Treasurer
G. Pennington Egbert III, Chair,
Development Committee
Stanley Fahn, M.D.
Richard Field
Guido Goldman, Ph.D.
Stephanie Goldman
Girija Muralidhar, Ph.D.
Daniel Novak, Ph.D., Chair
Leslie Peters
Blair Ford, M.D.
Melissa Barry
Staff Writer
Margaret DeJesus
Jay Phillips
Marilyn Phillips, P.T.
Paul Rohrlich, Ph.D.
Judi Sechter
A.C. Woolnough, Vice Chair
Alan B. Zimmerman
Arlene Levine
Mindy McIlroy
Robert Melzer
Gail Milhous
Michael S. Okun, M.D.
Timothy A. Pedley, M.D.
Gregory Romero, Secretary
please recycle