Parkinson's disease

"We are tremendously excited by these results which take us closer to making a diagnostic test for Parkinson's Disease that could be used in clinic"

"As a person with Parkinson's, it's hugely frustrating to think that one decision can actively hold back research that holds promise to transform lives. Patients with neurodegenerative diseases dream of the day when disease-modifying treatments are found, instead of therapies that simply mask symptoms. Disease-modifying therapies create the possibility of newly diagnosed patients never having to experience full-blown disease. The Michael J. Fox Foundation has long championed the scientific freedom to pursue all promising paths to finding these treatments. Biomarker discovery and stem cell science are among the innovative areas of biomedical research that hold potential to speed progress. So while our foundation gears up to launch its most ambitious biomarker discovery project to date, the Parkinson's Progression Markers Initiative, with ADNI as a precedent, we'll also be standing with Parkinson's patients, their loved ones and the majority of Americans who want us to move beyond political agendas and advance the promise of stem cell research."

"The intestine is one of the first affected organs in Parkinson’s disease (PD). PD subjects show abnormal staining for Escherichia coli and α-synuclein in the colon. ... In PD, the number of Lactobacillus was higher, while the sum of analyzed bacteria, Clostridium coccoides group, and Bacteroides fragilis group were lower than controls. Additionally, the sum of putative hydrogen-producing bacteria was lower in PD. A linear regression model to predict disease durations demonstrated that C. coccoides group and Lactobacillus gasser subgroup had the largest negative and positive coefficients, respectively. As a linear regression model to predict stool frequencies showed that these bacteria were not associated with constipation, changes in these bacteria were unlikely to represent worsening of constipation in the course of progression of PD. In PD, the serum lipopolysaccharide (LPS)-binding protein levels were lower than controls, while the levels of serum diamine oxidase, a marker for intestinal mucosal integrity, remained unchanged in PD. ... The permeability to LPS is likely to be increased without compromising the integrity of intestinal mucosa in PD. The increased intestinal permeability in PD may make the patients susceptible to intestinal dysbiosis. Conversely, intestinal dysbiosis may lead to the increased intestinal permeability. One or both of the two mechanisms may be operational in development and progression of PD."

"Parkinson’s disease primarily affects the central nervous system, but autopsy and small patient studies have revealed autonomic nervous system pathology in most cases. We looked for α-synuclein pathology in routinely acquired biopsies from patients and matched controls. Immunocytochemistry was performed and assessed blind to the clinical diagnoses. ... This large scale study demonstrates that accumulation of α-synuclein in the gastrointestinal tract is a highly specific finding that could be used to confirm a clinical diagnosis of Parkinson’s disease. We have shown that α-synuclein accumulation occurs prior to the onset of motor symptoms in the upper, as well as the lower gastrointestinal tract, remains present in serial biopsies until the onset of motor symptoms and is predominantly composed of phosphorylated α-synuclein."

"The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson’s disease (PD). … In addition to increased local inflammatory activity in the intestine, there is also evidence of increased systemic inflammatory activity in Parkinson’s disease. Thus, the working group around Williams-Grey and Bordacki detected increased levels of proinflammatory cytokines such as TNF-α, INF-gamma, IL1-β, IL-2, IL-4, IL-6 and IL-10 within the blood of PD patients … In this context, it has already been suspected that proinflammatory cytokines lead to a disruption of the blood-brain barrier and consequently are indirectly involved in the activation of glial cells … in a mouse model of PD transplantation of the microbiome of patients with PD into receptive mice led to motor symptoms as opposed to the transplant sample of healthy individuals … Furthermore, recently it has also been shown that gut-associated bacteria differ in their ability to decarboxylate levodopa to dopamine via tyrosine decarboxylases in the proximal small intestine and thereby influence the levodopa dosages needed for symptom control … In this regard, a conserved tyrosine decarboxylase (TyrDC) has been detected within Enterococcus faecalis … In addition, a negative correlation between the frequency of Firmicutes and the use of entacapone has been reported … These data suggest that in future the microbiome might be a crucial component in the management of side effects as well as in the therapy of PD."

"It has been established (Inaudible) for example, for Parkinson disease, you can use fetal brain cells from an abortus(?), or for treating diabetes, you can use eyelet cells from corpses. That works, this cure to the patients. The problem is, you need for one patient, for one Parkinson patient, the ... six abortuses, fetal brains, and there are not enough corpses to supply the needy patients with eyelet cells. The conclusion from all this is that only embryonic stem cells could provide the cells needed for an effective medical application."

"The propensity to lean forward becomes invincible, and the patient is thereby forced to step on the toes and the fore part of the feet, whilst the upper part of the body is thrown so far forward as to render it difficult to avoid falling on the face."

"For the past 15 months we have been engaged in a long-term study of the effects of levodopa on 60 severely disabled patients with Parkinson's disease, half postencephalitic and half idiopathic, who have been institutionalized for many years in our chronic disease facility. In common with published reports (summarized in an editorial in Brit Med J 1:446-447, 1970) we have found that the drug was effective, though to a varying degree, in the majority of our patients. However, in contrast to these reports we have observed that the period of benefit has been of limited duration and has been followed in all cases by adverse effects, the latter often progressive, sometimes serious, and occasionally dangerous."

"All patients with Parkinson's disease learn tricks of various sorts—to "unfreeze" themselves, to initiate and control motion, to transfer tremor and rigidity from limb to another, etc, etc. Such tricks or strategies, were analysed in detail by A R Luria in the 1920s and by James Pardon Martin (especially in his 1967 book, The Basal Ganglia and Posture), but these analyses would not have been possible without the aid of patients."

"While the etiology and pathogenesis of Parkinson’s disease (PD) is still obscure, there is evidence for lifestyle factors influencing disease risk. Best established are the inverse associations with smoking and coffee consumption. In other contexts there is evidence that health effects of lifestyle factors may depend on gut microbiome composition."

"The International Parkinson and Movement Disorder Society Evidence‐Based Medicine Committee's recommendations for treatments of PD were first published in 2002, updated in 2011, and now updated again through December 31, 2016. … The evidence base for treating a range of nonmotor symptoms in PD has grown substantially in recent years. However, treatment options overall remain limited given the high prevalence and adverse impact of these disorders, so the development and testing of new treatments for nonmotor symptoms in PD remains a top priority."

"Intestinal inflammation has been suggested to play a role in development of Parkinson’s disease (PD) and multiple system atrophy (MSA). To test the hypothesis that IBD is associated with risk of PD and MSA, we performed a nationwide population-based cohort study. ... This nationwide, unselected, cohort study shows a significant association between IBD and later occurrence of PD, which is consistent with recent basic scientific findings of a potential role of GI inflammation in development of parkinsonian disorders."

"Parkinson’s disease (PD) is a devastating and highly prevalent neurodegenerative disease for which only symptomatic treatment is available. In order to develop a truly effective disease-modifying therapy, improvement of our current understanding of the molecular and cellular mechanisms underlying PD pathogenesis and progression is crucial. For this purpose, standardization of research protocols and disease models is necessary. As human dopaminergic neurons, the cells mainly affected in PD, are difficult to obtain and maintain as primary cells, current PD research is mostly performed with permanently established neuronal cell models, in particular the neuroblastoma SH-SY5Y lineage. This cell line is frequently chosen because of its human origin, catecholaminergic (though not strictly dopaminergic) neuronal properties, and ease of maintenance."