Parkinson’s Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects

Ramprasad, Chethan; Douglas, J. Yellowlees; Moshiree, Baharak

doi:10.1007/s11938-018-0201-3

Cited by 22 publications

(17 citation statements)

References 136 publications

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“…It is also of relevance that some ghrelin receptor agonists have moved to clinical trials for gastroparesis and constipation (Acosta et al, 2015; Mulak and Bonaz, 2015; Shin and Wo, 2015; Mosińska et al, 2017). Collectively, these findings suggest that ghrelin agonists may be of benefit to alleviate PD symptoms (Ramprasad et al, 2018).…”

Section: Introductionmentioning

confidence: 95%

Multiple Beneficial Effects of Ghrelin Agonist, HM01 on Homeostasis Alterations in 6-Hydroxydopamine Model of Parkinson’s Disease in Male Rats

Minalyan

Gabrielyan

Pietra

et al. 2019

Front. Integr. Neurosci.

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Background and objective : Developing therapy for non-motor symptoms of Parkinson’s disease (PD) is important for improving patients’ quality of life. Previously, we reported that the ghrelin receptor agonist, HM01 normalized the decreased 4-h fecal output and levodopa-inhibited gastric emptying in 6-OHDA rats, and activated selective areas in brain and spinal cord. In this study, we evaluated whether chronic HM01 treatment influences motor functions and/or has beneficial effects on non-motor symptoms including alterations of body weight and composition, defecation, feeding and water intake in 6-OHDA rats. Methods : Male rats were microinjected unilaterally into the medial forebrain bundle with either vehicle or 6-OHDA. Three weeks later, we assessed basal body weight, and 24-h fecal output (pellets, weight, dry weight and water content), water intake and food intake (ingested and spillage). Then, HM01 (3 mg/kg) or vehicle was given per gavage daily for 10–12 days and the same parameters were re-assessed daily. Motor behavior (stepping and rotations tests), body composition were monitored before and after the HM01 treatment. Results : 6-OHDA rats showed motor deficits in rotation test induced by apomorphine and stepping test. They also displayed a significant reduction in body weight, water consumption, fecal weight and water content and an increase in food spillage compared to vehicle microinjected rats. Daily oral treatment of HM01 did not modify motor alterations compared to vehicle but significantly increased the body weight, fat mass, and 24-h fecal weight, fecal water content, food and water intake in 6-OHDA rats, while HM01 had no significant effect in vehicle microinjected rats. Fecal weight and water content were both correlated with water intake, but not with food intake. Fat mass, but not body weight, was correlated with food intake. HM01 effects were significant after 24 h and remained similar during the treatment. Conclusions : Chronic treatment with ghrelin agonist, HM01 improved several non-motor symptoms in the rat PD model induced by 6-OHDA lesion including the decrease in body weight, water consumption, fecal weight and water content, and increased food intake while not improving the motor deficits. These findings provide pre-clinical evidence of potential benefits of ghrelin agonists to alleviate non-motor symptoms in PD patients.

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Section: Introductionmentioning

confidence: 95%

Multiple Beneficial Effects of Ghrelin Agonist, HM01 on Homeostasis Alterations in 6-Hydroxydopamine Model of Parkinson’s Disease in Male Rats

Minalyan

Gabrielyan

Pietra

et al. 2019

Front. Integr. Neurosci.

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“…Nevertheless, a very recent randomized and controlled study showed that domperidone may be a safe and effective therapeutic for remission of symptoms in children with abdominal pain predominant functional gastrointestinal disorders (19). Domperidone has also been used for patients with gastroparesis (20,21), and have proved to improve success rate of enteral nutrition in the intensive care unit (18,22).…”

Section: Discussionmentioning

confidence: 99%

Can domperidone decrease transit time of pediatric video capsule endoscopy? A randomized controlled trial

Wu¹,

Xue²,

Huang³

2021

Transl Pediatr

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Background: The complete examination rate of video capsule endoscopy can be increased by reduced gastric transit time (GTT) and or small bowel transit time (SBTT). This study aims to examine whether the prokinetic domperidone reduces GTT and/or SBTT in pediatric patients undergoing video capsule endoscopy (VCE).Methods: We performed a single-center randomized controlled trial (n=200) to evaluate the effect of domperidone on GTT and SBTT among pediatric patients in a tertiary university-affiliated hospital for children. We explored whether patients randomized to domperidone had increased GTT, SBTT (primary outcomes) or higher complete examination rate (secondary outcome). The safety outcomes were the adverse effects in the domperidone group. This study was registered on ClinicalTrials.gov (NCT03662113).Results: Demographic features including gender and age were similar between the 100 patients of the domperidone group and the 100 patients of the control group. The median GTT was 67.5 minutes (44.8-117.5) in the domperidone group and 80.0 minutes (42.0-128.0) in the control group, while the median SBTT was 317 minutes (231-436) and 323 minutes (225-426), respectively. There were no significant differences in GTT (P=0.49) and SBTT (P=0.52) between the two groups. The complete examination rate was 97% and 98% in the domperidone and control groups, respectively (P=1.00).Conclusions: Domperidone shows no effect on GTT, SBTT and complete examination rate in pediatric patients receiving VCE.

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“…Antibiotics as treatment regime in PD have mostly focussed on targeting constipation and gut dysbiosis. Antibiotics such as rifaximin with poor systemic absorption may be used to treat small bowel bacterial overgrowth, which is also observed in PD [236]. Particularly, minocycline may have some neuroprotective activity in various experimental models including PD, [28,237,238].…”

Section: Antibiotics and Probioticsmentioning

confidence: 99%

Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease

et al. 2020

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Neuronal lesions in Parkinson’s disease (PD) are commonly associated with α-synuclein (α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems of patients, with the enteric nervous system also being especially vulnerable. Here, we bring together evidence that the development and presence of PD depends on specific sets of interlinking factors that include neuroinflammation, systemic inflammation, α-Syn-induced cell damage, vascular dysfunction, iron dysregulation, and gut and periodontal dysbiosis. We argue that there is significant evidence that bacterial inflammagens fuel this systemic inflammation, and might be central to the development of PD. We also discuss the processes whereby bacterial inflammagens may be involved in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that iron chelation, pre-and probiotics, as well as antibiotics and faecal transplant treatment might be valuable treatments in PD. A most important consideration, however, is that these therapeutic options need to be validated and tested in randomized controlled clinical trials. However, targeting underlying mechanisms of PD, including gut dysbiosis and iron toxicity, have potentially opened up possibilities of a wide variety of novel treatments, which may relieve the characteristic motor and nonmotor deficits of PD, and may even slow the progression and/or accompanying gut-related conditions of the disease.

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Parkinson’s Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects

Cited by 22 publications

References 136 publications

Multiple Beneficial Effects of Ghrelin Agonist, HM01 on Homeostasis Alterations in 6-Hydroxydopamine Model of Parkinson’s Disease in Male Rats

Multiple Beneficial Effects of Ghrelin Agonist, HM01 on Homeostasis Alterations in 6-Hydroxydopamine Model of Parkinson’s Disease in Male Rats

Can domperidone decrease transit time of pediatric video capsule endoscopy? A randomized controlled trial

Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease

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