The Growing Epidemic of Parkinson’s Disease in the Netherlands: Bas Bloem’s Optimistic Mission to Find a Cure

Bas Bloem starts with the bad news. In the Netherlands, the number of people with Parkinson’s disease has grown by 30 percent in ten years. There are now a total of 63,500 people with this incurable disease in the Netherlands. “And it is worldwide doubled, while Alzheimer’s stabilizes after adjustment for age. Parkinson’s is the fastest growing brain disease.”

Anyone who receives the diagnosis knows that things will not get better: not only exercise, but also sleeping, thinking and sex deteriorate. Many patients become depressed. It is striking that someone who has to deliver bad news so often manages to radiate so much optimism. With the mentality of the premier league volleyball player he once was, he says: “My fierce ambition is for the Netherlands to become the first country without Parkinson’s.”

There is no lack of support. Bloem, professor of neurology at Radboud University Medical Center, received the highest award in Dutch science last year, the Stevin Prize of 2.5 million euros. Including for his research into fall prevention, which means that Parkinson’s patients break their hip much less often. “He calls it the “Stevin team bonus”. Bloem is surrounded by forty PhD students, and more studies are being conducted under his supervision than he can mention, all over the world.

This Thursday afternoon, the team at Radboud University Medical Center is mainly busy organizing a large event Parkinson Weekend (September 22-24) that he offers to patients and the city of Nijmegen. With lectures, art, film, dance, music, sports and an organic dinner. He doesn’t want to call it a gift. “It remains a shitty disease.”

Eight genes

The reason for this conversation was the continuing stream of publications about ways to detect Parkinson’s early, long before the first symptoms appear – slower movement, stiffness, walking differently, shaking. Studies on biomarkers in cerebrospinal fluid, blood and intestines, scans that show abnormalities in the retinaresearch into damage to the DNA of mitochondria (the energy factories of cells), motion meters those risks show years before Parkinson’s manifests itself. These are all steps towards an increasingly earlier diagnosis.

But first that growth. “I see something new,” wrote James Parkinson in 1817, when he saw people “tremble with paralysis.” “Before that time, only rare cases were described,” says Bloem. An older population means more Parkinson’s, but what Bloem means: the growth cannot be explained solely by aging. “Eight genes together cause approximately 10 percent of Parkinson’s. One of those eight genes, the GBA mutation (glucocerebrosidase), is eight thousand years old. If that were the cause, we would have seen it before, so there must always be a risk factor involved. If you give that mutation to mice and you give them a pesticide, they will become twice as sick.”

Bloem published about it this year trichloroethylene, used in laundries and dry cleaners. And he calls paraquat, a pesticide that is still permitted in the US. “And air pollution in the broadest sense of the word. All linked to Parkinson’s,” says Bloem.

Also read: ‘Parkinson is partly a man-made disease’

Irreversible

As a scientist, he knows, you cannot simply speak of a causal relationship. “But when you see that it did not occur before industrialization and farmers and gardeners have a greater risk. If you know that these substances destroy the Parkinson’s area in the brain in mice. And when… I think about my PhD research. Seven Californian addicts injected a homemade type of heroin. That stuff, MPTP, looks exactly like paraquat. Those seven young men immediately developed the end stage of Parkinson’s after the needle, irreversibly. Those three stories together make me think that pesticides cause Parkinson’s. Parkinson’s is one man made disease.”

There are also protective factors. People who exercise a lot throughout their lives, follow a Mediterranean diet and drink a few cups of coffee every day have a lower risk. Not recommended, but striking: smokers are also less likely to develop Parkinson’s. “Possibly because smoking makes the intestines and nasal epithelium less permeable to pesticides,” says Bloem.

Omens

In Parkinson’s, nerve cells in the ‘black core’ in the middle of the brain die at an accelerated rate. These cells produce dopamine, the signaling substance that is important for movement. If the dopamine level becomes too low, the symptoms that make Parkinson’s so visible occur. But it may have been dormant for twenty or thirty years. “And when the diagnosis comes, almost 70 percent of the dopamine area is already destroyed,” says Bloem. “That also explains why all attempts to slow down Parkinson’s in that phase have failed so far.” That is why so much research is now focused on the signs, on the prodromal phase: constipation, reduced sense of smell and a lot of exercise during deep dream sleep. A little later comes asymmetrical shoulder pain and depression, and only then do motor skills.

Parkinson’s is called a brain disease, but it might be better to speak of a systemic disease, Bloem explains. The brain is attached to the vagus nerve, the nerve highway between the brain and the intestines, at the bottom of the brain stem. “The idea now is that Parkinson’s spreads in the form of incorrectly built proteins, alpha-synucleins. The stacked proteins, which accumulate in Lewy bodies, leave the diseased nerve cell, enter a healthy nerve cell and make it sick too. What we now think is that in many people Parkinson’s starts in the intestines and reaches the bottom of your brain stem via the vagus nerve. That’s where the dream center is. That’s where the sleep disorder starts. In the meantime, the wave expands and reaches the Parkinson’s area at the top of the stem. Eventually it also reaches the cerebral cortex. Then you become demented and everything goes wrong.”

Mess

Alpha-synuclein is not only found in the cerebrospinal fluid, but also in the blood. And researchers are finding it in the skin, in the intestines, even in salivary glands. Bloem has just come from a conference in Copenhagen. “They were at each other’s throats over a new definition of Parkinson’s.” Better call it ‘neuronal alpha synuclein disease’, a number of experts thought. Not a good idea, Bloem thinks. “There are many patients who do not have that protein accumulation and do have all the symptoms. Moreover, you label people as patients who may never develop Parkinson’s.”

There are probably two types of Parkinson’s, says Bloem. “One variant starts in the brain and is more genetically determined. The other comes through the intestines or by inhalation – that is, through junk.” Research has been done on mice that developed less severe Parkinson’s disease with sterilized intestines and which became more seriously ill with transplanted feces from a Parkinson’s patient. And with A large group of Swedes whose vagus nerve was severed in the 1950s to inhibit stomach acid showed much lower rates of Parkinson’s.

It is clear that the composition of the intestinal bacteria in Parkinson’s is different: more inflammatory markers are visible in these people. “One explanation is that pesticides directly change the microbiome, another is that you get constipation because the nerve cells are damaged years before the first symptoms, and that changes the microbiome.” Eventually, everyone with Parkinson’s will develop constipation, but for some it starts with that, and for others it comes later.

Intensive exercise

Nowadays, with medications that stimulate dopamine release and broad care with a variety of therapists, symptoms can be treated quite well and patients have been given more good years of life. But most studies into slowing or preventing the disease yield little. “The only exception, and I am proud of it, is our comparative study of intensive exercise.” Half of the participants had to get their heart rate up considerably on an exercise bike three times a week. The control group only received stretching exercises. Two years later, brain scans in the control group showed shrinkage in the brain. “The decline in the sports group had stopped. The Parkinson’s areas also made new connections with the healthy cerebral cortex. And the great thing is, this process is not concerned with that alpha-synuclein mechanism.”

How quickly people deteriorate cannot so much be explained by dopamine, Bloem thinks, but by how well the cortex still functions. “Perhaps in the manifest phase we should no longer focus on the dopamine system, which is already almost completely broken, but on protecting the cortex. Exercise is now the first and only treatment that can tentatively claim to slow progression.”

That sounds promising, but how can you exercise if your body no longer wants to? For that reason alone, Bloem is extremely excited about the study that is being started with Stevin money to anticipate that moment. People with a REM sleep disorder, reduced sense of smell or lazy intestines – all possible signs – receive a game via smartwatch and telephone that gives the wearer simple movement commands. Alpha-synuclein and other markers are measured to see whether they develop more favorably in athletes than in the control group. “Very exciting, because no one comes to the hospital anymore. We all measure vibrations and inertia, for example, via the smartwatch. It can go wrong in a hundred ways and it can only go right in one way. Will it work remotely? Is it possible to motivate people who are not yet ill to change their behavior?”

Disease inhibiting drugs

Then another question: what good is it to hear at the age of fifty that you will probably get Parkinson’s, without the prospect of a medicine that prevents or cures the disease? “There is an ethical dilemma,” Bloem readily admits. “If you report to a sleep center with a REM sleep disorder and Bas Bloem comes by to explain that you have a 60 to 70 percent chance of developing Parkinson’s, you also create unrest. But for science we want to gather evidence, from associations to causation. We give people the opportunity to contribute to this.”

Who knows, disease-inhibiting drugs may emerge. In the meantime, testing for genetic predisposition is already easy, and yet most people don’t want to know, says Bloem. “It’s not necessary. Whether you have those genes or not: everyone benefits from healthier eating and exercise and less exposure to pesticides.”

A version of this article also appeared in the September 23, 2023 newspaper.
2023-09-21 12:46:06
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