Thread by @Limits2Growth

Disclaimer: this is not a qualified scientific statement, just our opinion after reading the BBC story.

“Prof Jog believes Parkinson's disease reduces the signals coming back to the brain - breaking the loop and causing the patient to freeze.”

bbc.com/news/health-47…

If Parkinson’s Disease is a consequence of problems with the feedback loops, this could have major implications for research and for the quality of life of patients.

Our body is a very complex system that relies on potentially thousands of féedback loops.

Every single physiological function that keeps us alive, in motion and healthy depends on a complex network of feedback loops. Temperature, blood pressure, heartbeat, hunger, sleep, movement, smell, hearing, waste, immunity, decisions, emotions, you name it.

We tend to associate Parkinson’s with tremors and movement problems. Patients often are treated by Movement Disorder Specialists. But over the years our understanding of the condition has evolved and it is now viewed as a systemic problem.

For patients this translates to an ever increasing list of symptoms that get worse over time. From balance to tremors, from bladder to bowel, from sweat to saliva, from smell to vision, from mood to anxiety, from sleep to apathy, from decision to depression, the list goes on.

For the medical profession it’s challenging to find a proper medication combination for an array of moving targets. Each medication adds its own list of side effects. The most effective drug treatment was discovered in the 60’s and tends to wear off. And there’s no marker.

Exercise and other treatments help but it’s hard to keep a patient motivated under such circumstances. R&D @ScienceofPD has made steady progress. There seems to be enough funding. Folks like MJ Fox and others have certainly played a key role in keeping the flow steady.

But results are slow. The challenges range from the blood brain barrier, to measuring results in the absence of a marker, to understanding the pathogenesis and the pathology, to differentiating symptoms from side effects to recruiting enough people for clinical trials.

The most significant progress seems to be Deep Brain Stimulation, a invasive surgical procedure that inserts electrodes deep into the brain to deliver electrical signals that help keep the tremors under control. But researchers still don’t know why it works and long term impact.

Other than that, there have been new ways of delivering existing medication, repurposing of approved drugs for other conditions. And that’s about it. For the patient in advanced stage the condition is probably very close to unbearable. Doctors say you don’t die of Parkinson’s.

From a system dynamics perspective, skepticism arises. We know that a complex system where feedback loops progressively and relentlessly break down will most likely reach a tipping point and collapse. The most rational decision would be to voluntarily turn the system off.

Except that in the case of rational humans, this path is still a taboo, very much like abortion. A handful of countries allow their citizens to make this kind of choice. But why are we discussing Parkinson’s in the first place? Because this new approach could be a game changer.

As systems professionals observing the resting tremors of some Parkinson’s patients we would probably think: “Hmm, these tremors look like oscillations. This could be due to noise or delay in the feedback.” Such an observation completely reverses the research path.

As per the BBC story “we had thought that the movement problems occurred in Parkinson's patients because signals from the brain to the legs were not getting through”. If this is true, the research community has been looking to the wrong direction. This has major implications.

Wild speculation ahead. To begin with, there’s opportunity for collaboration. The Parkinson’s community can instantly leverage the incredible body of knowledge that has been developed by the SD people. This includes systems principles, modeling best practices, simulation tools.

Second, current Parkinson’s drugs focus on dopamine replacement. Their effects can be somewhat limited. For example, levodopa - considered the gold standard - might be effective to alleviate tremors but could have negligible impact on bowel movements.

But researchers know that the disease affects other neurotransmitters and existing drugs don’t target these other at all. If indeed there’s a feedback problem, by stimulating other nervous feedback paths, this approach could potentially alleviate other symptoms.

Third, this approach could reduce the need for medication, in all stages. This has major implications for those patients with early onset. Long term use of some Parkinson’s treatments result in debilitating side effects like dyskinesia or dystonia.

Another debilitating effect of long term treatment are motor fluctuations. Over time the effects of the medication become a lot less predictable. Significant motor fluctuations occur because of the long path from the digestive system to the brain.

Fourth, as per the story, the treatment showed some persistence that could be related to neural plasticity - the ability of the brain to change over time according to usage. There’s a potential negative feedback know as “use it or lose it” that could be reversed.

Fifth, if indeed Parkinson’s is caused by feedback problems, this would result in a significant shift in the focus of ongoing and new research. Different questions would have to be investigated creating new opportunities, including collaboration with the SD community

Sixth, the direct stimulation of nerves creates a direct path to the brain that can be explored. For example, patients could wear monitoring devices to measure vital signs and adjust the stimulation parameters accordingly.

Of course, this is all wild speculation. We truly hope the new research confirms it’s potential. System Dynamics has evolved into a robust and incredibly versatile approach to study complex dynamic feedback systems. We look forward to increasing our collaboration in this matter.