motor symptoms

Stool transplant could improve motor symptoms in Parkinson’s disease

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stool transplant syringes
A small new trial suggests that stool transplants could be a helpful treatment option in early-stage Parkinson’s disease.
  • Parkinson’s disease is one of the leading causes of disability worldwide, and while treatment options are available, they can become less effective over time.
  • A recent paper has highlighted the potential effect of fecal transplants on motor symptoms, which are one of the main markers of Parkinson’s disease.
  • The study could pave the way for further research into the role of the gut microbiome on neurodegenerative conditions, say experts.

Fecal transplants could have an effect on the motor symptoms of people with Parkinson’s disease, a recent study suggests.

A small, single-center clinical trial carried out in Belgium found that people with Parkinson’s disease who received a single dose of a fecal transplant from a healthy donor, had improved symptoms compared to those who received a placebo.

Results, published in eClinicalMedicine, suggested that the motor score for people who received a donor transplant had improved by 5.8 points after 12 months, compared with an improvement of 2.7 points in people who received a placebo transplant.

Significant improvements were also found for an objective measure of constipation (colon transit time), although there was no significant difference in patient-reported scores for constipation.

Mild gastrointestinal symptoms were a common negative side effect at the time of the transplant and were more frequently observed in people who received the donor transplant. Donor transplant recipients were also more likely to have worsened fatigue after 12 months.

Fatigue: A negative side effect of fecal transplantation?

For the study, a total of 22 participants with early-stage Parkinson’s disease received the transplants from healthy donors, and 24 received their own fecal matter as a placebo, as part of the GUT-PARFECT trial carried out at Ghent University Hospital, Belgium between December 1, 2020 and December 12, 2022.

The fecal transplant for both the treated cohort and the placebo cohort was delivered via a tube inserted in the jejunum, a part of the small intestine, via the nose.

Researchers followed up with the participants at 3, 6 and 12 months post-transplant. They collected data on gastrointestinal symptoms, non-motor symptoms, depression and anxiety, sleep and fatigue, and cognition.

While people who received fecal transplants from healthy donors registered improvements in their motor symptoms, they appeared to experience increased fatigue.

The reason for this negative effect was unclear, said lead author of the study Patrick Santens, MD, PhD, professor of neurology at Ghent University Hospital.

“We don’t have a good explanation [for this phenomenon], but suspect that inflammatory mechanisms may be involved. Fatigue is prevalent in inflammatory gut disorders,” he told Medical News Today.

Can ‘placebo’ fecal transplants also help?

One of the limitations of the study is that a strong placebo effect was observed, potentially because the placebo treatment was likely to have been viewed as invasive by the participants.

There is evidence to suggest that the more invasive a placebo treatment is, the greater the placebo effect.

It was also possible that some of the effect seen in the placebo group, was not just placebo effect, Santens suggested:

“The placebo effect was quite large. This may be due to the nature of the treatment with large expectations, on the one hand. On the other hand, there is preliminary evidence that [fecal transplant] with one’s own stool might also have a limited positive effect, at least on gut function. Therefore, we will try placebo treatment with colored inactive solutions in the next steps.”

The gut-brain axis in Parkinson’s disease

Small improvements have been seen in other trials of fecal transplants in Parkinson’s disease patients.

Herbert DuPont, MD, clinical professor of medicine – infectious disease at Baylor College of Medicine, Houston, TX was the first author of a paper published in Frontiers In Neurology in 2023, which showed that fecal transplants could have some effect on the symptoms of Parkinson’s disease.

He was not involved in this latest research, but in commenting on its findings for MNT, he explained that disturbances to the microbiome in Parkinson’s disease patients have been known about for years, and there are various ways in which the gut can affect Parkinson’s disease.

“One is through the central nervous system, through the vagus nerve to the enteric nervous system through spinal nerves to the brain, and that’s direct neural connections.“ he said.

“The other way is through the immune system. Eighty percent of immune cells of the body are in the gastrointestinal tract, and our immune response is dependent on a healthy microbiome,“ DuPont added.

“And then the final thing is hormone production,“ he told us. “Chemicals, biochemicals and metabolites produced by the microbes go through the bloodstream or through the vagus nerve to the brain and have an effect. These three routes are all very important.”

Braak’s hypothesis of Parkinson’s disease

Relevant to the context of this research is Braak’s hypothesis of Parkinson’s disease, which proposes that Parkinson’s disease starts to develop when a pathogen enters the body through the nose, reaches the gut, and initiates the accumulation of alpha-synucleinTrusted Source in the nose and the digestive tract.

Some researchers think that this then spreads to the nervous system and brain, potentially causing Parkinson’s disease.

DuPont explained:

“We believe that neural connections are very important in the movement of alpha-synuclein, the small protein that is involved in producing cell death in the brain. And this is the so-called Braak’s hypothesis. And I think this is correct, but I think the biochemicals are very important. And I think the immune system is very important.”

Single dose of fecal matter could improve symptoms

“I thought [it] was very important to show that a single dose [fecal transplant] could have a durable effect,“ DuPont told us, commenting on the study findings.

“I felt if it was a chronic disease where there are genetic disorders and chronic changes in the body then you would have to give [fecal matter] multiple times to have an effect and that’s been the way we’ve done our studies. But this shows that [even] one dose will have an effect,” he added.

Multiple dosing may necessitate providing the transplant via capsules, for example, which would involve processing the fecal matter in a way that might destroy many of the cells, microorganisms, enzymes and biochemicals that could be beneficial.

Previous research conducted by DuPont looked at transplants carried out with fresh, frozen, and freeze-dried fecal matter. “This study has given me an encouragement to think about giving, maybe, frozen or fresh samples in the future,“ DuPont told us.

“I think the Parkinson’s studies are a lead into [similar research for] other neurodegenerative disorders. Multiple sclerosis and Alzheimer’s may well follow, and may well have a similar success story,” he hypothesized.

Santens told us that the team behind the latest study was conducting further research into the microbial compositions of the different participants in relation to the recent study outcomes.

“We hope to get funding for a larger and multicenter trial, taking into account the findings of this pilot trial […] We are also looking at patient profiles to potentially delineate subgroups that might be optimal candidates for this treatment,” he told us.

Pharmacological Treatment of Parkinson Disease A Review.

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Importance  Parkinson disease is the second most common neurodegenerative disease worldwide. Although no available therapies alter the underlying neurodegenerative process, symptomatic therapies can improve patient quality of life.

Objective  To provide an evidence-based review of the initial pharmacological management of the classic motor symptoms of Parkinson disease; describe management of medication-related motor complications (such as motor fluctuations and dyskinesia), and other medication adverse effects (nausea, psychosis, and impulse control disorders and related behaviors); and discuss the management of selected nonmotor symptoms of Parkinson disease, including rapid eye movement sleep behavior disorder, cognitive impairment, depression, orthostatic hypotension, and sialorrhea.

Evidence Review  References were identified using searches of PubMed between January 1985 and February 2014 for English-language human studies and the full database of the Cochrane Library. The classification of studies by quality (classes I-IV) was assessed using the levels of evidence guidelines from the American Academy of Neurology and the highest-quality data for each topic.

Results  Although levodopa is the most effective medication available for treating the motor symptoms of Parkinson disease, in certain instances (eg, mild symptoms, tremor as the only or most prominent symptom, aged <60 years) other medications (eg, monoamine oxidase type B inhibitors [MAOBIs], amantadine, anticholinergics, β-blockers, or dopamine agonists) may be initiated first to avoid levodopa-related motor complications. Motor fluctuations may be managed by modifying the levodopa dosing regimen or by adding several other medications, such as MAOBIs, catechol-O-methyltransferase inhibitors, or dopamine agonists. Impulse control disorders are typically managed by reducing or withdrawing dopaminergic medication, particularly dopamine agonists. Evidence-based management of some nonmotor symptoms is limited by a paucity of high-quality positive studies.

Conclusions and Relevance  Strong evidence supports using levodopa and dopamine agonists for motor symptoms at all stages of Parkinson disease. Dopamine agonists and drugs that block dopamine metabolism are effective for motor fluctuations and clozapine is effective for hallucinations. Cholinesterase inhibitors may improve symptoms of dementia and antidepressants and pramipexole may improve depression. Evidence supporting other therapies for motor and nonmotor features is less well established.

Answering Questions on Deep Brain Stimulation.

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Answering Questions on Deep Brain Stimulation

NOTE: The medical information contained in this article is for general information purposes only. The Michael J. Fox Foundation has a policy of refraining from advocating, endorsing or promoting any drug therapy, course of treatment, or specific company or institution. It is crucial that care and treatment decisions related to Parkinson’s disease and any other medical condition be made in consultation with a physician or other qualified medical professional.

The most common surgical treatment for Parkinson’s disease is deep brain stimulation (DBS). Similar to available drug treatments, DBS does not slow down the disease or restore sick and dying nerve cells affected by Parkinson’s disease, but rather offers symptomatic benefits. In DBS, a thin electrode is implanted into the brain, targeting motor circuits that are not functioning properly. Small electrical pulses from a device similar to a cardiac pacemaker are then used to stimulate a small brain region and block the signals that cause some Parkinson’s symptoms.

This past November, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) hosted a Webinarfeaturing Dr. William J. Marks, Jr. discussing DBS. Participants in the Webinar had additional questions which Dr. Marks has answered below:

MJFF: When in the disease course is DBS recommended?
WM: The standard answer is that DBS is intended to be used for “advanced Parkinson’s disease,” but that phrase isn’t all that practically helpful and may be misleading. A better way to think about DBS candidacy is that it should be considered when motor problems produced in PD (slowness, stiffness, shaking, walking problems, wearing off of medication, fluctuations of motor symptoms, dyskinesia) are no longer sufficiently treated by an optimized medication regimen.
MJFF: How does a physician decide whether to recommend DBS?
WM: A physician will assess the extent to which PD motor symptoms are sufficiently controlled (from the patient’s perspective) to determine whether and when to recommend DBS. One effective means for assessing this is to consider what percentage of the day motor symptoms are adequately controlled and what percentage of the day they are not. If motor symptoms present difficulty for a significant extent of the day (perhaps 20 percent or greater) it may be an indicator of insufficient medication control. Another important factor is how severe motor symptoms are when they do emerge, and the extent to which they interfere with a person’s ability to engage in the everyday activities of a patient’s life.
MJFF: Can DBS be performed too early or too late in the course of PD?
WM: Currently, many would consider the use of DBS to be “too early” if all PD motor symptoms for a patient were adequately controlled through the entire day with a medication regimen that produced no unacceptable side effects. “Too late” refers to the concept that in the later stages of PD, for some patients, they may develop symptoms that do not respond to medication or to DBS, such as severe balance problems or significant cognitive difficulties. These resistant symptoms might be responsible for disability and their persistence would overshadow any benefit to motor symptoms that DBS might provide. If a patient has become severely disabled for a long period of time, it may be more difficult to “rescue” individuals than it would have been to use DBS as a preventative measure.
MJFF: Is there an age limit for DBS?
WM: There is no absolute age cut-off for use of DBS although some centers find that older (70 or above) patients may not experience as robust a response as younger patients. Other factors (such as types of symptoms present, responsiveness to levodopa, cognitive function) are probably more important to consider than age per se.

MJFF: What symptoms does DBS treat? Which does it not treat?
WM: Most patients find that DBS is just as effective as a successful levodopa regimen in treating:

  • Slowness or lack of movement (bradykinesia and akinesia)
  • Stiffness of muscles (rigidity)
  • Shaking of the limbs (tremor)
  • Gait problems that remain responsive to levodopa
  • Mild balance problems that remain responsive to levodopa
  • Motor fluctuation (variations in level of motor symptoms and their control by medication)
  • Dyskinesia (involuntary, excessive movements of the body, usually occurring when medications peak)
  • Dystonia (painful abnormal muscle activation that causes toe curling or twisting of hand or feet)
  • Nighttime motor symptoms that emerge due to lack of frequent medication doses
  • Body pain from PD (sometimes)

As with levodopa, DBS does not typically improve:

  • Speech problems
  • Swallowing problems
  • Cognitive problems
  • Mood problems (depression, anxiety)
  • Freezing of gait or other movement that occurs when medications are working at their best
  • Moderate or greater balance problems
  • Bladder, bowel, or sexual dysfunction

MJFF: How common are infections associated with DBS?
WM: Clinical experience and formal studies commonly show an infection rate of three to four percent. Such infections most commonly occur in the chest region at the site where the neurostimulator (“pacemaker”) is implanted. Infections most commonly occur weeks or months after the surgical procedure to implant the device. Treatment usually entails removal of the device component in the infected area, treatment with intravenous antibiotics, and then re-implantation of a brand new replacement device. In cases where the infection involves the chest region, usually the brain leads can be left in place (as long as the infection has not spread), so that no additional brain surgery would be required. Rarely, infection can originate in the brain at the level of the electrode which can be more serious, and in some cases require the removal and re-implantation of the electrode.

MJFF: What causes the infections?
WM: Any time the human body is opened during surgery—and particularly when foreign objects like medical devices are inserted inside—bacteria and other organisms can enter, grow, and cause an infection. Other possible sources of infection arise from the bloodstream and can “seed” other parts of the body, though this mechanism is less likely.