Unanswered Questions In Parkinson’s Disease Research

Here are some of the most important unanswered questions in Parkinson’s disease research from some of the leading figures in the field. This post first appeared on the Tomorrow Edition website

Sara Riggare

Why are most patients tremor dominant?

Prof. Bas Bloem

Why do rates of progression differ so much between different patients?

Why do patients with a tremor, which is an extra motor sign, have a better prognosis than those without?

Why do some people develop freezing of gait?

Why are there such prominent gender differences in Parkinson’s disease?

Prof. John Hardy

Are alpha-synuclein deposits the cause or consequence of something deeper wrong with neurons?

Prof. Andrew Lees

Is the presence of Lewy bodies at post-mortem essential to confirm the diagnosis of Parkinson’s disease or can it occur without them?

Can we diagnose Parkinson’s disease in the absence of bradykinesia?

Dr. Peter Schmidt

Most genes identified are linked to risk of Parkinson’s but not how it manifests and the rate of progression. What biological factors contribute to the progression rate?

What factors contribute to the risk of cognitive change in PD, which seems to be largely absent in about 50% of cases?

How much do we have to knock down extracellular alpha-synuclein to measurably slow cell to cell transmission (if this approach even works)? Is, for example, a 99% reduction enough?

Dr. Simon Stott

Why does the condition progress so slowly?

Why are some cells in the brain more vulnerable than others?

Why does the condition affect men more than women?

Prof. Gerold Riempp

Is PD really a single illness or is it rather a group of different ailments that all lead to somewhat similar symptoms in the end?

How big is the influence of genetic components of PD?

Why is the incidence of PD lower in countries closer to the equator?

Is there a single way of curing PD?

Prof. Joel Watts

Can we develop an accurate animal model of PD?

Does spreading of protein aggregate pathology contribute to disease progression in PD?

Prof. Roger Barker

When does Parkinson’s disease begin?

Why do some patients with PD do so well?

Does alpha-synuclein really have prion like properties in patients with PD?

Prof. Tanya Gurevich

What is the trigger which activates the cascade of neurodegeneration?

Add your own questions in the comments below!

“The important thing is to not stop questioning. Curiosity has its own reason for existing.”
– Albert Einstein

“What interests me in life is curiosity, challenges, the good fight with its victories and defeats.”
– Paulo Coelho

Team P.R.A.G.

We are an international group of 8 people, connected by Parkinson’s Disease, aiming to influence the Parkinson’s Disease research agenda through research advocacy. We have been working together as a team for nearly a year. Each of us brings significant experience, activism and stamina to the advocacy table. Our group, as well as our readers on social media, is bound together by the urgent need of over 6 million people of a future without the ever increasing burden of Parkinson’s Disease.

2 thoughts to “Unanswered Questions In Parkinson’s Disease Research”

  1. How many sub-groups/phenotypes are there? What are the implications for clinical trial design?

    If PwP have lost 70-80% of substantia nigra neurons already at diagnosis, how does the SN apparently function pre-diagnosis with so much loss?

    Why do symptoms vary so much from day to day?


  2. Great questions Kevin, I know this is kind of a rhetorical exercise, but I wanted to try and answer your questions….

    – Nobody knows how many subgroups there are, some experts say each case is unique and need to be treated as such, some say that they all fall under the same general category and that we may be able eventually devise one treatment to more or less treat everyone. Certainly an unanswered question, though there are many attempts being made to answer this question, most using a person’s genetic makeup, to develop clinical trials for specific sub-types.

    – This one I believe does have an answer, we just haven’t filled in all of the exact details of the answer yet. The brain has all sorts of compensatory mechanisms that allow us to function properly, even when there is significant damage to a certain area. Also, evolution has given us an overabundance of dopamine production in that area because it ‘knows’ that as we age some of those cells will become more vulnerable and lose their function. For most people, that aging just happens at about the same rate as the rest of their body and they never notice any impairment. So, if somehow has a loss of only 40% of dopamine production from the substantia nigra, they don’t see any of the symptoms that we call Parkinson’s because there is either enough dopamine coming from other areas to compensate for that loss, and/or we just don’t need a 100% to function properly. Only when a certain threshold of dopamine production is loss (50-80%), do we start to see symptoms of this disease we call PD.

    – The short answer, cus we are incredibly complex machines and every part of us is in some way related to the whole system that keeps us alive and healthy. There are so many factors that go into how a person feels, and how one’s symptoms of a particular disease might manifest themselves which change slightly every day, that we just don’t have the ability to keep track of them all. To do so we need to take into account all food one eats that brings nutrients to every cell in your body, any virus that one’s immune system might be fighting off, how much sunlight one was exposed to that now pumps the vitamin D hormone throughout the body, etc. etc. etc….it would really be an almost endless list of factors that we would need to account for if we really wanted to understand the day to day changes of a person’s symptoms.

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