Status of research in PD: Is there hope? – Webinar notes

Status of research in PD: Is there hope? – Webinar notes

In early June, Stanford Parkinson’s Community Outreach offered a webinar on the current status of research on PD, featuring Brent Bluett, DO, a movement disorders specialist at Stanford. He covered research efforts so far in PD, what is in the near-term and long-term pipelines for PD treatment, and how people can learn more and get involved in research. There was also a question and answer session. We at Stanford Parkinson’s Community Outreach viewed the webinar and are sharing our notes.  

The webinar was recorded and can be viewed here.

If you have questions about the webinar, you can contact Stanford Parkinson’s Community Outreach at (650) 724-6090 or Robin Riddle, Stanford PD Support, at rriddle@stanford.edu.

Dr. Bluett mentioned several ways to get involved and participate in research:

  • The Michael J. Fox Trial Finder is a free online tool that helps match people with clinical studies. Learn more here.
  • The US National Library of Medicine provides an online database where you can search for clinical trials by diagnosis, geographic area, and recruitment status.
  • The Davis Phinney Foundation highlights research related to PD and offers grants.
  • The Parkinson’s Foundation also funds and highlights current PD research.

Now… on to our notes from the webinar.

– Lauren

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Status of research in PD: Is there hope? – Webinar notes

Presented by Stanford Parkinson’s Community Outreach

June 2, 2020

Summary by Lauren Stroshane, Stanford Parkinson’s Community Outreach

Dr. Brent Bluett is a movement disorders specialist at Stanford. He started with an overview of PD and its increasing incidence in the worldwide population, then discussed research efforts so far, current and future areas of research, lessons from Huntington’s disease, and what those with PD can do now.

The motor symptoms of PD are familiar to most: tremor, slowed movement (bradykinesia), stiffness (rigidity), and, often, imbalance. The neurotransmitter dopamine acts as fuel for the brain, allowing different brain regions to communicate with each other and permitting smooth, purposeful movement. In PD, the neurons (brain cells) that normally produce dopamine start to die off, depriving the brain of this necessary neurotransmitter. In addition, clumps of abnormal proteins called Lewy bodies start to collect in the brain, likely contributing to neuronal death. The protein that makes up these Lewy bodies is called alpha-synuclein.

Cases of PD continue to climb; in 1990, 2.5 million people had PD, compared to 6.1 million people with PD in 2016. Neurological disorders are the biggest source of disability worldwide, and PD is the fastest growing of these diseases.

There are a number of different ways to go about reducing the incidence – the number of cases – of PD:

  • Prevention, by increasing physical activity earlier in adulthood and reducing exposure to pesticides and other chemicals known to increase the likelihood of developing PD
  • Improving access to care and treatments, such as levodopa
  • Increasing research funding to understand the underlying causes of PD and develop new therapies

Since PD is on the rise globally, governments should accordingly increase funding to research this disease.

Types of research for treating PD

Past research into treatment of PD can be grouped into broad categories:

  1. Prevention or delay of disease progression
  2. Symptomatic monotherapy (treatment of symptoms with a single drug)
  3. Symptomatic adjunct therapy to levodopa: (treatment of symptoms with levodopa and another drug)
    1. In early or stable PD
    2. In PD patients optimized on treatment for specific or general motor symptoms
  4. Prevention or delay of motor complications (motor fluctuations and dyskinesia)
  5. Treatment of motor complications (motor fluctuations and dyskinesia)

Treatment of non-motor complications

What has research shown to date?

So far, dietary or nutritional supplements such as coenzyme Q10, creatine, and vitamin D remain popular, but there is no evidence of clinical benefit for PD. Physical exercise has also recently been investigated as a method of disease modification in PD:

  • Preclinical studies suggest dopamine cell loss is reduced with exercise
  • Exercise promotes brain derived neurotrophic factor (BDNF), growth factors that may help neurons stay healthy
  • Results of studies to date are mixed but the studies were generally low quality
  • Therefore, the clinical practice implication is “investigational”

Research into exercise has suggested it may be beneficial for slowing progression of PD, but much of the evidence is underwhelming or inconclusive. This may be in part due to the many confounding factors and limitations in how we study this currently; for instance, we don’t have a way to objectively monitor motor symptoms such as tremor or slowness. Most studies do not yet separate out participants according to PD stage or type of symptoms. It is widely recognized that PD presents very differently among individuals, and that it may actually represent more than one disease. Not to mention, there are many different types of exercise! Perhaps certain types or frequencies of exercise are more beneficial than others; there are many variables.

All of these factors mean research into the impact of regular exercise in those with PD has opportunities for improvement; most movement disorders specialists still believe exercise to be very beneficial and important for their PD patients.

Research on neuroprotective agents

Ultimately, no studies so far have identified a clinically useful intervention to prevent or delay progression of PD.

Several epidemiological studies have found an inverse correlation between tobacco smoking and risk of PD; the NIC-PD clinical trial evaluated the potential of transdermal nicotine to modify disease progression in early PD, but concluded that transdermal nicotine does not slow progression in early PD and may worsen symptoms of PD.

Levodopa in early Parkinson’s disease (LEAP) trial

The “ELLDOPA” trial demonstrated that patients with early PD still received clinical benefit from levodopa two weeks after the medication was stopped. It was unclear whether this was meant the disease itself had been modified in those patients, or if the symptom relief was simply more prolonged than expected.

The “LEAP” trial randomized patients into two groups:

  • carbidopa-levodopa for 80 weeks (early-start group)
  • placebo for 40 weeks followed by carbidopa-levodopa for 40 weeks (delayed-start group)

Results showed no difference in the severity of symptoms between the early-start group versus the delayed-start group. There was no significant difference between the rates of dyskinesia and levodopa-related motor fluctuations at 80 weeks between the early-start and delayed-start groups.

Opportunities for improvement in PD research

We have no truly objective measures of disease progression in PD. Having a biomarker that could be detected in the blood, some type of imaging that could count healthy dopamine-producing neurons, or devices that track and measure motor symptoms would greatly help scientists to study and draw conclusions about disease progression. Currently, movement disorder specialists use clinical rating scales such as the UPDRS, which are useful but not objective; they do not provide data about subtle changes.

We also cannot yet account for the different subtypes that are likely present within PD, which presents very differently between different people. Some have tremor; some don’t. Some have significant imbalance earlier in the disease; others don’t. Certain PD subtypes might respond better to certain treatments, and might have different expected progression of their disease. Most clinical trials do not account for these subtypes, which may greatly affect the accuracy of the data.

Additionally, most interventions – such as drug trials – are tested on patients with early motor symptoms of PD. But studying interventions in the prodromal phase – very early in the disease, before the motor symptoms have fully manifested – would likely prove more effective. This is because those therapeutic interventions might be more effective in people with less‐advanced pathology, who have more health dopaminergic neurons remaining, for instance.

Early identification of Parkinson’s disease

Prodromal features of PD occur long before the onset of motor symptoms, sometimes developing years before a diagnosis of PD is made:

  • REM sleep behavioral disorder (RBD)
  • Constipation
  • Anosmia (lost sense of smell)
  • Excessive daytime sleepiness
  • Orthostatic hypotension (drops in blood pressure due to changes in posture)
  • Urinary dysfunction
  • Erectile dysfunction
  • Depression
  • Anxiety without depression

Over 90 percent of PD patients have an impaired sense of smell at the time of diagnosis. Twenty percent of the general population, by contrast, suffers from decreased sense of smell.

Smell tends to be fairly normal in those with atypical parkinsonian syndromes, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and drug-induced parkinsonism.

REM sleep behavior disorder (RBD) seems to be another strong indicator of the presence of alpha-synuclein pathology; fifty to seventy percent of patients with confirmed RBD are found to develop a synucleinopathy.

Constipation is very common in the general population, so it is certainly not diagnostic for PD. Yet those with constipation have a 2.3 to 4.5 times higher likelihood of developing PD.

Dr. Bluett reported that criteria identified by the Movement Disorders Society (MDS) for prodromal symptoms of PD are 98.8 percent specific in predicting later development of Parkinson’s disease. You can read more about the MDS criteria here.

Eventually, rather than trying to find interventions that slow progression of PD, we hope to study how to prevent its development in the first place.

Targeting alpha-synuclein to prevent disease progression in Parkinson’s disease

In pre-clinical lab studies, cell-to-cell transmission of the harmful forms of alpha-synuclein protein can be blocked, which is encouraging. Human clinical trials of monoclonal antibodies and vaccines against alpha-synuclein have begun.

These include the PASADENA and SPARK studies, which will be discussed further, along with the AFFiRiS study.

  • Monoclonal antibodies against toxic αlpha-synuclein
    • PASADENA — phase 2 study of RG7935/PRX002 (Prothena/Roche)
    • SPARK — phase 2 study of BIIB-054 (Biogen)
  • Active immunization against αlpha-synuclein
    • AFFITOPE subcutaneous vaccine PD01A and PD03A (AFFiRiS)

Monoclonal antibodies against toxic αlpha-synuclein in Parkinson’s disease

The PASADENA study is a phase 2 study evaluating the efficacy of a monoclonal antibody drug called Prasinezumab (RO7046015/PRX002) in individuals with early-stage PD. It is the first anti-alpha-synuclein antibody with the potential to be disease-modifying to be evaluated for efficacy in patients with PD. The drug targets alpha-synuclein and is designed to slow the protein’s misfolding and decrease the spread of abnormally-folded alpha-synuclein in the brain.

The drug showed promise in various cellular and animal models of related disease. The PASADENA study is active but no longer recruiting at this time.

Another study evaluating a monoclonal antibody is the SPARK study, a phase 2 clinical trial evaluating the safety and efficacy of BIIB054 in those with PD. It is also active but no longer recruiting.

Immunization against toxic αlpha-synuclein in PD

The prospect of someday having a vaccine against pathological misfolding alpha-synuclein is exciting. The AFFiRiS study is aphase 1 clinical trial evaluating the safety and tolerability of the AFFITOPE subcutaneous vaccine. Studies of PD01A and PD03A, two versions of the vaccine, have been completed.

Much like the influenza vaccine, it prompts the body to produce alpha-synuclein antibodies. PD01A triggered an immune response in 19 of 22 (86%) of vaccinated subjects. Of those, 12 of the 19 developed alpha-synuclein antibodies in their blood. This suggests the injected vaccine successfully produced antibodies against alpha-synuclein.

A phase 2 trial of PD01A will start soon, with study locations to be announced.

Targeting alpha-synuclein to prevent PD progression

There are a number of different research approaches to combating the spread of alpha-synuclein. Companies Neuropore Therapies and UCB have sponsored a trial of drug NPT200-11 to prevent alpha-synuclein from aggregating.

Studies of the drug nilotinib, a chemotherapy agent, have evaluated whether it can prevent alpha-synuclein clumping and improve clearance of the protein. A small phase 1 trial at Georgetown university demonstrated proof-of-concept and suggested the treatment may improve motor skills and cognitive function in those with PD. Then a phase 2 study of this drug met its primary objectives, demonstrating that nilotinib is safe and tolerated for those with PD. Next, Phase 3 trials will be conducted, with study sites still to be determined.

Lastly, the family of drugs known as β2-adrenoreceptor agonists shows some potential for decreasing the expression of the protein alpha-synuclein. Drugs that may be studied include salbutamol and clenbuterol.

Genetic therapies to prevent PD progression

Dr. Bluett feels genetic therapies may be the most promising among the different areas of PD research. Potential genetic treatments for PD tend to focus on genetic mutations that have been most clearly linked with PD, including LRRK2 and GBA mutations. Denali Therapeutics is funding a phase 1 study of small molecules DNL201 or DNL151 to see if inhibiting LRRK2 activity in patients with that mutation could safely treat PD. The phase 1 trial was successful, however, there are concerns about long-term toxicity to the lungs and kidneys from these drugs.

For those with a mutation in the GBA gene, there are a number of relevant drug studies:

  • GZ/SAR402671 — glucosylceramide synthase inhibitor. This is a GBA enhancer in patients with early-stage PD carrying a GBA mutation (MOVES-PD — Sanofi/Genzyme); ClinicalTrials.gov ID#: NCT02906020.  
  • Ambroxol (AiM PD) — inhibitory chaperone that refolds and upregulates Glucocerebsidase and enables its transport to the lysosomes and their exocytosis, which leads to reduction of αlpha-synuclein (ClinicalTrials.gov ID#: NCT02941822).
  • CSF administration of AAV9 vector carrying the normal GBA gene (Medpace/Prevail.

Lessons from Huntington’s disease (HD)

We can learn some lessons from research into HD, a neurodegenerative disorder that had no FDA-approved medications until 2008. The genetic causes of HD are well understood, and are confined to just one gene, providing a highly specific target for therapies.

The medication tetrabenazine (Xenazine) was approved for treatment of HD chorea in the US in 2008, but had already been in use in the UK since 1971. Then, in 2017, the medication deutetrabenazine (Austedo) was approved for HD chorea as well.

The GENERATION-HD1 trial, sponsored by Roche and Genentech, evaluated the safety and tolerability of the huntingtin-lowering drug BN40423. This is an antisense oligonucleotide therapy (ASO). In a group of 46 early onset HD patients, the drug lowered levels of the mutant protein associated with HD by up to 60 percent, a dramatic and exciting result with the potential to reverse HD symptoms. A phase 3 clinical trial of this drug is now in progress and Dr. Bluett is honored to be involved.

He pointed out that, until the last 12 years, we had no treatments specifically for HD symptoms at all. Due to the identification of the specific gene mutation that causes HD in 1993, scientists have been able to come up with drugs that target the underlying causes of this disease. This is a useful lesson for PD: once we gain a better understanding of the science and genetics of PD (which is a far more heterogeneous disease than HD), it will be easier for scientists to target the causes rather than just the symptoms.

Other possible targets to prevent the progression of PD

The following are other areas of research in PD that Dr. Bluett did not have time to discuss in detail, and which seem less immediately promising:

  • Altered calcium homeostasis with the drug isradipine (phase 3 trial, STEADY-PD)
  • Iron chelation with the drug deferiprone (phase 2 trial, FAIRPARK II) deferasirox, deferoxamine
  • Insulin resistance with the drug exenatide (glucagon-like peptide 1 receptor agonist)
    • Oxidative stress with MAO-B inhibitor drugs selegiline, rasagiline, and safinamide, as well as inosine — phase 3 trial (SURE-PD)
    • SURE-PD 3 trial discontinued early due to lack of signal efficacy
  • Autophagic dysfunction with sirolimus, trehalose, MSDC-0160, retinoic acid derivatives, enhance transcription factor EB by beta-cyclodextrins or by genetic overexpression
  • Lysosomal dysfunction with drugs NCGC758 and NCGC
  • Mitochondrial dysfunction with drug EPI-589 (NCT02462603)
  • Neuroinflammation with autologous adipose-derived stromal stem cells (NCT01453803)

What can someone with PD do while waiting for a cure?

Eating a Mediterranean diet is likely to be beneficial for those with PD, based on evidence in neuroscience, nutrition, and other areas of medicine. This means consuming non-refined cereals and grains, fruits, vegetables, legumes, potatoes, fish, and healthy fats like olive oil, while limiting intake of red meat, poultry, and full-fat dairy products. Research suggests the Mediterranean diet is associated with a lower probability of prodromal PD, as well as lowered risks of depression, constipation, daytime sleepiness, and urinary dysfunction. It may be that the antioxidant and anti-inflammatory effects of this diet may help prevent degeneration of neurons and clumping of alpha-synuclein into Lewy bodies.

Despite the mixed results from exercise studies, it is highly probable that exercise improves the symptoms of PD in those who already have it. Dr. Bluett recommends at least 30 to 45 minutes of exercise a day, 4 to 5 days per week. The best options provide aerobic exercise, working your cardiovascular system, and designed to improve balance and stability:

  • Bicycling (a stationary bike is fine and carries less risk of falls)
  • Walking, jogging, or running are safe as tolerated
  • Tai Chi or yoga
  • Swimming

Make sure your existing PD treatment is optimized. Talk to your movement disorders specialist to make sure you are on the medications that will provide you the maximum benefits with the fewest side effects. Stay informed about new therapies that are being developed, and keep yourself in the best shape you can.

Lastly, stay up to date on current research!Talk with your healthcare provider about ongoing clinical trials that may be right for you. Dr. Bluett recommends seeing a movement disorders specialist who is aware of or is participating in clinical trials.

You can also enroll in the Michael J. Fox clinical trial finder.

Search clinicaltrials.gov for relevant trials that are currently recruiting in your area.

Review the websites of other organizations dedicated to helping those with Parkinson’s disease:

Discuss studies you are interested in with your movement disorders specialist.

Main takeaways:

  • The incidence of Parkinson’s disease is increasing rapidly. This will encourage greater funding into research for a cure.
  • Several promising therapies are being studied:
    • Targeting alpha-synuclein by monoclonal antibodies or immunization
    • Gene modifying therapy
  • Remember the lessons from Huntington’s disease: there was nothing for a long time, then important treatments came along.
  • Continue to live a healthy lifestyle by eating right and exercising frequently
  • Optimize your condition with the help of your movement disorders physician
  • Stay up to date on current research efforts

In conclusion: yes, there is hope!

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Question and Answer Session

Q: What does “DO” stand for, and are you a movement disorders specialist?

A: Dr. Bluett gets this question a lot; it stands for “Doctor of Osteopathic Medicine.” It is nearly the same training as a medical doctor (MD), except that he also learned about osteopathic manipulative treatment (similar to chiropracty or massage therapy) during his training as well, and a more holistic approach. He still did an MD residency and fellowship, has worked in movement disorders for many years, and is a movement disorders specialist.

Q: Given the Covid-19 pandemic, what is the status of research and funding for research at the present time?

A: Basically, it means there was a delay. Clinical trials have been halted at most sites in the country and around the world, which has delayed but not stopped things. If we have been paused for six months, it means the study is delayed by six months, not generally anything more concerning than that. Even here in the Bay Area, research is starting to ramp up again.

Q: What country is considered the cutting edge of PD research?

A: It’s hard to say, but probably Europe in general. The FDA is important; it protects us, but also delays and prohibits things to ensure safety. European countries tend to be a bit more “cutting edge” than the US in terms of medical research.

Q: How does research on inherited (genetic) PD inform our knowledge of idiopathic (non-genetic) PD?

A: By understanding genetic forms of PD, we can better understand the “downstream” effects that we see in PD by understanding the “upstream” causes.

Q: Are there clinical trials for PD going on in the Bay Area right now?

A: Absolutely! Among others, Dr. Chad Christine at UCSF is currently doing a trial to slow degradation of dopamine in the brain. You can learn more here.

Recently, Stanford was one of the sites for the PASADENA study, which is no longer recruiting.  

There are some other studies coming up that he could not go into detail about yet.

If you are living in the Bay Area, you are in a good place to participate in studies: UCSF, Stanford, and the Parkinson’s Institute all do a lot of research.

Q: What triggers the death of neurons in the substantia nigra? Is it changes in the microbiome, caffeine, inflammation, insomnia, or environmental toxins?

A: All of the above, including mitochondrial degeneration and clumping of misfolded alpha-synuclein proteins as well.

Q: When can we expect a cure for PD?

A: Dr. Bluett started practicing in movement disorders 5 years ago, after his fellowship training. At that time, many people expected a cure in 5-10 years. We are working hard, but it has all taken longer than many hoped. The research pipeline in the US is long; once we find a potential cure, it will still have to go through the standard vetting with the FDA to ensure its safety. Now, he thinks we are looking at about a decade before something is here and readily available for all who need it.

Q: What do autopsy studies reveal about medication-resistant PD? Deep brain stimulation (DBS) in the STN has controlled my symptoms well, though levodopa did not.

A:  It is unusual to get DBS if you did not have a response to levodopa, but that is great you are receiving benefit from it. At this time, he does not know of any studies specifically looking at this question.

Q: Is there any “proof of concept” for slowing or eliminating PD?

A: Yes, there have been thousands; translating them into reality is the challenge. For research, we have cellular models, mouse models, and then humans; there is often a big gap between getting potential treatments to translate effectively between them.


Q: What organizations or institutions are leading the way in the cure or treatment of PD?

A: The Michael J. Fox Foundation is highly involved in research; the Davis Phinney Foundation is a great resource to look to as well.

Q: What do we know about whether PD causes dementia? My wife has PD; how can I know if her dementia is caused by her PD?

A: PD can cause dementia, often called Parkinson’s disease dementia (PDD). If she has PD and dementia, then the dementia is likely due to her PD. We think this is because the Lewy bodies have spread out into the cortex of the brain, affecting cognition. However, we are finding now that it is possible to have both PD and Alzheimer’s disease (AD) pathology at the same time. It may not be possible to know for sure. A neurologist or a neuropsychologist may be able to help identify what cognitive tasks she struggles with, which can give insight into what type of dementia she is experiencing.

Q: What is the status of research on stem cell therapy to replace lost dopaminergic neurons?

A: There was a lot of excitement about this initially, but injected stem cells tended to take on the characteristics of the PD cells they were intended to replace, and didn’t end up producing dopamine. Now, instead of using human fetal tissue cells, researchers are using human pluripotent stem cells (HPSCs). Dr. Bluett recently read a review about the current status of this in the journal Nature, which indicated that this research still has a ways to go before it may be practical and effective. Efforts are ongoing.


Q: Is it safe to go to Ireland or Australia to participate in research, for instance in drug trials of Immufloxin?

A: From the limited information he could find online, this drug appears to be an immunosuppressant, similar to a chemotherapy agent, which can be quite dangerous. This should be vetted first in phase 1 and 2 trials to ensure it is safe for humans. Unfortunately, there are a lot of people who will take advantage of those with PD. It is best to seek treatment and research involvement in well-known, academic medical centers. You should be able to participate in research without paying any money.

Q: What role does the DaTscan play? What does it cost?

A: A DaTscan is most useful for trying to differentiate PD from atypical parkinsonism, such as MSA, PSP, or CBS. It is fairly accurate – perhaps slightly more so than a movement disorders specialist – at diagnosing PD. However, it can be prohibitively expensive, sometimes thousands of dollars out of pocket, depending on your insurance.

Q: How does PD compare with essential tremor (ET)?

A: The type of tremor is generally a bit different; those with ET typically experience “action” tremor that occurs when they are trying to perform an action, such as grabbing a cup of water. Those with PD tend to have “resting” tremor that is more prominent when resting the hand. ET only causes tremor, not other motor symptoms or non-motor issues. For someone who has only a tremor and no other features of PD, they may have ET. Complicating matters, sometimes those with ET can go on to develop mild PD as well.

Q: Is ocular instability used to make a diagnosis of PD?

A: No, ocular instability is more commonly found in cerebellar disorders or in PSP.

Q: If Sinemet (carbidopa-levodopa) has no effect on my tremor, is it a good idea to stop taking it or reduce my dose to decrease the risk of developing dyskinesias down the road?

A: Yes, if your only PD symptom is a tremor, then why take a medication if it isn’t benefitting you?

Q: How can I tell if Sinemet is working? I do not see much noticeable difference after three years. Should I go up or down on the dose?

A: Ideally, you should very gradually increase Sinemet to avoid triggering side effects while getting used to the drug; this gradual titration can mean it is difficult to notice improvement at first. If you haven’t noticed any progression of your PD symptoms in 3 years, then likely the Sinemet is doing something. It may be having more of an effect than you think it is. One way to tell is to gradually decrease the dose (under the guidance of your doctor) to see if you notice any worsening of your PD symptoms.

Q: What are the alternatives to Sinemet if it isn’t well tolerated?

A: There are several; there are options such as dopamine agonists, such as pramipexole (Mirapex); MAO inhibitors such as rasagiline (Azilect); or Amantadine, among others.

You should discuss this with your movement disorder specialist to see what is likely to work best for you.

Q: What are treatments for dementia? Does it matter if it is PD dementia or some other type of dementia?

A: There are a number of medications that show modest benefit for dementia symptoms, typically cholinesterase inhibitors. It does matter whether the dementia is likely related to PD or not; other medications may be more useful for Alzheimer’s dementia. Rivastigmine (Exelon) or donepezil can be useful. Another medication, which is for PD psychosis specifically, is pimavanserin (Nuplazid).

Q: What is the future of DBS? Do you think closed-loop DBS is likely to offer a better quality of life, or just longer battery life?

A: Closed loop is likely the future of DBS. Its goal is to provide more tailored, adaptive therapy that should provide more effective stimulation therapy, which should improve quality of life.

Q: Is delaying the progression of PD a cure?

A: Great philosophic question. It is not truly a cure, but is still an important piece of the puzzle, particularly for those living with the disease now.

Q: How is insomnia treated?

A: It’s important to practice good sleep hygiene, such as keeping regular hours, not looking at bright screens right before bed, and having a quiet, restful sleep environment. Warm milk can be helpful due to the tryptophan. Exercise before evening.

[Editor’s note: The Stanford Parkinson’s Community Blog recently published a summary of a webinar on sleep issues in PD that may be relevant. You can access it here.]

Q: What is your opinion of the medicine ambroxol to reduce alpha-synuclein buildup?

A: Dr. Bluett was not aware of this medication.

Q: Don’t we need “good” alpha-synuclein? Wouldn’t a potential vaccine destroy the good alpha-synuclein along with the bad?

A: We look at intra-cellular (within the cell) and extra-cellular (outside the cell) versions of preventing the accumulation of alpha-synuclein. What we need to do is prevent the aggregation of big clumps of misfolded alpha-synuclein, while leaving alone the regular, healthy alpha-synuclein proteins throughout our body.

Q: How is Huntington’s disease (HD) related to PD?

A: HD is a fully genetic disorder in which a particular gene is repeated multiple times. They are not related in terms of pathology, but it is also a movement disorder, like PD, and can have a range of psychiatric and cognitive effects. The connection he wished to draw is simply that, for a long time, there were no real treatments for HD; then, in the last ten years or so, we suddenly have a lot of things on the horizon. The same could be true of PD.  

Q: Could you address some mental health issues in PD? How can friends and family members help people with PD who have mental health issues?

A: This can be really hard for everyone involved. Support is the most important thing to provide. Be supportive; understand what is part of the disease, and what is not. Remember that you are frustrated with the condition, not the person.

Q: How varied is the presentation of PD from one person to another?

A: There are a number of different ways we know of that PD presents, and there are likely others that we haven’t identified yet. This is being researched currently.

Q: How long, on average, do non-motor symptoms precede motor symptoms like tremor?

A: It can be 5-10 years before motor symptoms appear.

Q: Why does lack of smell/taste change throughout the day?

A: This is unusual; true anosmia – lost sense of smell – does not fluctuate at all.

Q: Can you talk about pain in PD?

A: This is a part of PD, due to the changes in the brain. Pain is more readily felt, and can be exacerbated by other factors such as depression or poor sleep.

[Editor’s note: The Stanford Parkinson’s Community Blog recently published a summary of a webinar on pain in PD that may be relevant. You can access it here.]