In early November, the Parkinson Society British Columbia hosted a webinar on Parkinson’s disease (PD) research with Dr. Rebecca Gilbert, the chief scientific officer of the American Parkinson Disease Association (APDA).  In this webinar, Dr. Gilbert discussed the funding fellowships and research grants APDA provides, and different areas of research the APDA prioritizes for research.

The main areas of research that the APDA focuses on include:

• Abnormal accumulation of alpha-synuclein
  • APDA research: how to stop accumulation of alpha-synuclein, molecular mechanisms of Lewy body pathology-associated cell deaths in PD
• Role of other cell types (not neurons, rather Glial cells, gut microbiome)
  • APDA research: understanding the role of glial cells in PD
• Brain circuitry:
  • APDA research: different and better ways to perform deep brain stimulation (DBS) regarding electro placements, DBS in early-stage PD
• The role of exercise in PD
  • APDA research: SPARX study, molecular underpinnings of neuroprotective effects of exercise
• Genetics
  • APDA research: genetic factors for PD in hispanics, differences between men and women with PD
• Digital biomarkers
  • APDA research: Digital biomarker algorithms for monitoring PD 

Dr. Gilbert presented research that highlighted the benefits of exercise in delaying PD progression.  For information on the benefits of exercise, as well as exercise videos and live exercise classes, please see these Stanford Parkinson’s Community Outreach webpages: 

Benefits of exercise

Exercise videos

Live exercise classes

Dr. Gilbert also explained research on the value deep brain stimulation (DBS) may provide for people with PD. For more information on DBS, please see this Stanford Parkinson’s Community Outreach webpage.

For a recording of this webinar, please see this Parkinson Society British Columbia YouTube webpage.

See my notes below of the November 10th webinar. 

Regards, 

– Joëlle Kuehn

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“Pioneering Parkinson’s Research from the American Parkinson’s Disease Association” – Webinar Notes

Speaker:  Dr. Rebecca Gilbert, chief scientific officer, American Parkinson Disease Association (APDA), New York City, New York

Webinar Host:  Parkinson Society British Columbia (PSBC)

Webinar Date:  November 10, 2021

Summary by:  Joëlle Kuehn, Stanford Parkinson’s Community Outreach 

APDA research funding:

• APDA provides funds to PD researchers that wouldn’t have ordinarily received funding
• Funding categories for individuals performing PD research:
  • George C. Cotzias fellowship
    • 3 years
    • Given to a physician scientist (sees patients and does research)
    • Designed to launch a career
  • Post-doctoral fellowship
    • 1 year
    • Just finished PhD, and will work in another persons lab, and need money to make themselves a good candidate to work in someone’s lab
  • Research grants
    • Renewable one year grant
    • Seed money to a an assistant professor level who has finished their post-doc, if they need money to get started
  • Diversity in PD research grant
    • Renewable 1 year grant
    • Someone studying PD in a community that has previously been understudied (women, rural populations, various ethnicities, native populations, etc.)
    • Vital because if we don’t understand PD in all its forms, we will miss out on fully understanding the condition in everyone    
• Also fund centers for advanced research
  • Money given to institutions that are performing PD research, and has a very advanced program going but may have some holes in their funding

PD research – preclinical and clinical:

• Pre-clinical research:
  • Research involving cells, animal models, etc.
  • Takes years
  • Finds the mechanism of what is going on on a molecular level, before seeing if it works on people
  • May or may not lead to a chemical or product to be used by people
  • Have to be open to failure because not everything will succeed and make it through
  • Vast majority do not make it through
• Clinical research:
  • Research involving people

Exciting themes in current research:

• Abnormal accumulation of alpha-synuclein:
  • We know the protein accumulates abnormalls in PD, think that the accumulation affects health of the cell and causes the cell to die 
  • A lot of research is on understanding how it accumulates, and how to make it not accumulate 
  • APDA current project:
    • Dr. Sunil Kumar – how to stop alpha-synuclein from accumulating in PD
      • If we know, we can develop therapies to block it
  • Past APDA project:
    • Dr. Vivek Unni
      • Molecular mechanisms of Lewy body pathology-associated cell deaths in PD
      • Demonstrated that alpha-synuclein plays a role in repair of damaged DNA
      • Understand more how alpha-synuclein affects non-PD people
      • Is a new role for alpha-synuclein and can broaden our understanding about what might happen to cause PD
• Role of other cell types (not neurons):
  • Brain is composed of many different types of cells, not just neurons
  • Supportive cells (ex. Glial cells)
  • May protect or inflame nerves
  • APDA project:
    • Dr. Abby Olsen – understand the role of glial cells in PD
      • Once we know, we can develop glial-based therapies for PD
• Brain circuitry:
  • In order to be productive, nerves need to talk to each other
  • Talk in circuits
  • Circuitry is complex 
  • APDA project:
    • Deep brain stimulation:
      • Neurosurgical procedure in which electrodes are placed deep within the brain to deliver electrical impulses to brain structures in order to improve PD symptoms
      • Electrodes are connected to implantable pulse generator (IPG) in the chest, which can be programmed remotely
      • Deep brain stimulation manipulates circuits, and goal is to try to make the abnormal PD circuitry act more like it should
    • Dr. Enrico Opri – looking for different and better ways to perform DBS, regarding electro placements (see if DLEP brain signals can be used to guide where the DBS electrode is placed during surgery)
  • Past APDA project:
    • Dr. Mallory Hacker – deep brain stimulation in early-stage PD
      • DBS is usually done in later stages of the disease, but Dr. Hacker studied DBS in early-stages
      • Long term clinical outcomes for DBS in early-stage PD
      • Participants in the early DBS + optimal medical therapy group did better at 5 years than those who received optimal medical therapy alone
• The role of exercise:
  • Known that exercise is important for PD
  • Research on why it is important, and understanding what exercise does to make PD better
  • APDA project:
    • SPARX study:
      • 128 early PD patients, not on dopamine medications were enrolled in either:
        • High intensity treadmill (4x/week, 80-85% max heart rate)
        • Moderate intensity treadmill (4x/week, 60-65% max heart rate)
        • Wait-list control group
      • After 6 months, high intensity group had a 0.3 point change in united parkinson’s disease rating scale (UPDRS), while the control group had a 3 point change
    • Dr. Constanza Cortes – why exercise is good for the brain:
      •  Molecular underpinnings of neuroprotective effects of exercise by determining effects of exercise on PD pathology in mouse brain
• Genetics:
  • We all carry genes from parents, and know that propensity to have medical conditions is dependent on the genes we inherent and our environmental exposures
  • Understanding how specific genes may contribute to PD risk
  • Past APDA projects:
    • Dr. Karen Nuytemans – genetic factors for PD in hispanics:
      • Novel variants in LRRK2 and GBA identified in Latino PD population
    • Dr. Elizabeth Disbrow – differences between men and women with PD:
      • Showed men with PD had significantly greater executive and processing speed impairments compared to women despise no differences in demographic variables or other measures of disease severity
• Digital biomarkers:
  • If you have a wearable device (ex. Watch, phone), it may capture information on your movements that can help you diagnose PD or follow trends in PD
  • Biomarkers can help understand how PD manifests in movements we can record
  • Past APDA project:
    • Dr. Yuanfang Guan – digital biomarkers for monitoring PD
      • Study developed algorithm to extract biomarkers of PD from mobile phone accelerometer and gyroscope data
      • Digital biomarkers for self-reported PD

Past research accomplishments of the APDA:

• Novel variants in LRRK2 and GBA genes identified in Latino PD cohort enriched for Caribbean origin
• Sex-specific cognitive differences in PD
• Severity-dependent effects of PD on perception of visual and vestibular heading
• Pedunculopontine nucleus degeneration contributes to both motor and non-motor symptoms of PD

Questions & Answers:

Question: Among research outputs on exercise, are we getting closer to more prescriptive exercise prescriptions?

Answer: We are getting closer to the prescription, exactly what you need to do for your case of PD. The CDC has put out guidelines, which are a recommended 150 minutes of moderate aerobic exercise per week, or 75 minutes of intensive aerobic exercise per week for all older adults along with weight bearing exercise. Moderate exercise means when you are exercising you can carry on a conversation, whereas with intensive exercise you cannot. In terms of additions for PD, the two additional features would be stretching and balance exercise. If that seems daunting, start small. Do tasks that you enjoy and that you know you will do regularly.

Question: Does high intensity exercise mean that running is better for me than walking?

Answer: Probably yes. We don’t want to discourage people and say only high intensity is good, that’s not true. All exercise is good. However, having the aerobic component where you are getting your heart rate going is probably best.

Question: Is there any relationship between exercise produced compounds and BDNF (a protein in the brain)?

Answer: What Dr. Constanza Cortes is working on is probably not going to end up being BDNF, but BDNF has been shown to be important in this process.

Question: Can you elaborate on the possibility of a chemical in a bottle?

Answer: This is so nascent and new that I don’t have much more to say. We just started funding this work, and there is more to come. The general idea is that there may be something produced in an exercising animal, possibly from the muscles, that is neuroprotective and can be harnessed and given to another person who is not doing that exercise.

Question: What are your thoughts on photobiomodulation therapy?

Answer: I don’t know enough about photobiomodulation therapy to answer that, but I have heard that there is light therapy for PD that may be helpful. 

Question: What is the role of the LRRK2 gene in PD development? Is there a test for that?

Answer: There is, you can get genetic testing and LRRK2 would be one of the genes that is tested. We do need to be careful because the different labs will test LRRK2 in different ways. The one way is to sequence the entire gene, the other way is to test for specific mutations, and so you need to know what test is being done to know exactly what information you’ve just received. If you are being tested for a specific mutation and it ends up that you don’t have that mutation, you might actually have that mutation somewhere else that wasn’t captured. If you get the entire gene sequenced, it might identify changes that are irrelevant (there are changes but they don’t have an impact).

Question: Thoughts on later stage alpha nuclear drugs or vaccines?

Answer: There are small molecules that are in clinical trials now, that are in humans, that are meant to break up alpha-synuclein accumulation. There are quite a few in clinical trials. Small molecules will be able to be taken orally. Regarding the concept of vaccines, one strategy to break up the alpha synuclein is giving an injection of either alpha-synuclein which then kicks the body to make antibodies against alpha-synuclein, which then is meant to keep the alpha-synuclein from sticking to each other, the antibody will block the alpha-synuclein and protect it from finding another molecule to accumulate with. 

Question: I have had DBS on both sides. It’s helping my tremor but it’s affecting my speech. Thoughts on this?

Answer: This is something reported, not everybody has this problem, but it has been reported. The way to address it typically is to try to find the DBS settings that don’t do this, that cause the good things from DBS and don’t cause the side-effects. There are today 3 companies and products that have much more advanced programming options than ever before.   

Question: I exercise 2-3 hours a day but haven’t seen a slowing in progression. Why?

Answer: Yes, this is an inexorable disease that progresses no matter what we do to a certain degree. The goal with exercise is not to stop progression, unfortunately, and in addition, there are some people whose progression is more aggressive than others. There is a lot of variability to progression, and a lot we don’t know about why one person progresses worse than another. Our general understanding of what exercise does is that it slows down the progression, it doesn’t stop the progression. In certain people it may not seem to be making a difference at all. There is  huge variability there. I think you’re making a critical point for everyone in that we tend to focus on the positives and the importance of exercise and what it can do, but we cannot ignore or deny the experience of people who don’t find exercise as helpful as we are saying it is, because of that variability.

Question: Do you think there will be a new drug that will be better than levodopa, as that is the gold standard?

Answer: It’s important to note that PD motor symptoms are due to the death of dopamine neurons, which means that someway or other, you need to have dopamine to normalize movement. It just so happens that that fact was discovered a long time ago. It doesn’t mean that dopamine isn’t important because it was discovered a long time ago. We need to replace dopamine, and that I think won’t change. There may be a better way to replace dopamine than giving levodopa. Researchers are working on that and we do think there is a better way to give dopamine in a more even way, instead of giving bursts of levodopa multiple times a day. There is a subcutaneous pump that is being developed, where levodopa is going to be introduced slowly instead of in bursts. There are drugs that release in a slow manner, which is important to introduce levodopa in a more natural and brain friendly way. I don’t think we’re ever going to be able to escape dopamine.

Question: How are the early stage people with PD identified?

Answer: There are many people identified early who don’t need medication, and that may vary based on where you live. It could be that people who have access to big medical centers are diagnosed early, but I don’t have the data on that. The push to identify PD at an early stage and getting an early diagnosis would be to get regular medical care, if your general doctor has familiarity with PD, if your family has familiarity with PD. If we do determine how vital exercise is in those early stages, then it will become even more important for everyone to be diagnosed at that early stage so that we can slow down the disease.

Question: Do you have any ongoing research studying the role of the microbiome?

Answer: The microbiome is the collective bacteria/virus/cellular organisms that live in our gut and affects our health in ways we haven’t fully appreciated or researched. People are starting to study if there is a specific microbiome for people with PD, and if there are specific bacteria that are under or over represented and what it does to the absorption of medication and developing the disease. There is a theory that PD starts in the gut. APDA has funded interesting projects about the microbiome.