In Development: Neuralink’s Brain Implants , to Treat PD

The latest invention from Neuralink is ultra-thin “threads” that could be injected into the brain to examine neuron activity. These brain-chip interfaces could hopefully be used to treat chronic conditions like PD. One of the goals of this new technology is to allow humans to keep up with the constant leaps and bounds of AI tech. So far there have only been animal trials of Neuralink’s new technology but with astounding results. Neuralink president, Max Hodak said that the company is close to clinical trials in neurological disorders.

The first human trials will focus on paralysis patients and will involve installing four of the new devices into the patient’s brains. If successful, Neuralink will probably release some developer API. The new technology has the potential for use on PD patients and could be used to improve deep brain stimulation therapy. Deep brain technology already exists but not at the level that Neuralink will hopefully be offering.

Source: Musk’s Neuralink close to clinical trials of “brain interface” device –

The Link Between Helicobacter Pylori and PD?

This 2018 report from the Journal of Parkinson’s Disease examines the association between the gut bacteria Helicobacter pylori and PD. H. pylori is a common gut bacterium that causes ulcers, gastritis, and can lead to stomach cancer. The majority of PD cases are caused by unknown environmental factors, and bacterial infections could be one of them. This has led doctors to look at the link between H. pylori and PD. After reviewing past studies on the subject four important points were noted: H. pylori-infected PD patients experience worse motor function issues than those not infected; people with PD are more prone to be infected by H. pylori and eradication of H. pylori could improve motor function and levodopa absorption in people with PD.

Source: Eradicating Helicobacter pylori Infections May Be a Key Treatment for Parkinson’s Disease

Types of Keto Testing, Blood Glucose Testing, and Types of Exogenous Ketones

Mike Mutzel from High Intensity Health (author of Belly Fat Effect) talks to Frank Llosa of KetoneAid. KetoneAid produces a Ketone Ester (raw beta-hydroxybutyrate (BHB) ketone) supplement that can get you into a deep state of ketosis within 30 minutes. You would have to fast or go on an intense ketogenic diet to reach the same ketosis state. There are different types of Keto testing, blood glucose testing, and different types of exogenous Ketones. Ketosis is influenced by BHB salts; Ketone supplements. There have been many discussions about the link between PD and the ketogenic diet. In one study PD patients were put on a ketogenic diet for a month and the results showed a 43% improvement in the Unified Parkinson’s Disease rating scale. There is no doubt that PD is affected by diet and nutrition so the ketogenic diet may offer relief from some symptoms.

Keto for PD: The William Curtis Story

Mike Mutzel from High-Intensity Health (author of Belly Fat Effect) talks to William Curtis about his PD journey and how a ketogenic diet changed his life. Curtis suffered from PD for over 17 years before he started exercising, fasting, and following a low-carb, ketogenic diet that remarkably improved his PD symptoms. Through trial and error, Curtis found the right balance in his diet. The William Curtis’ program for easing PD symptoms is not appropriate for everyone. For example, PD patients that have balance problems could do more harm to themselves if they followed Curtis’ diet. After 12 hours of fasting through the night, Curtis has a bulletproof coffee in the morning prepared with butter, heavy cream, coconut oil, and Stevia. This helps his PD symptoms and increases the ketone D-betahydroxybutyrate (BHB).

good results in rats
www.ncbi.nlm.nih.gov/pmc/articles/PMC4912670/

keto vs low fat
8 weeks
both diets had good results, keto was better
pubmed.ncbi.nlm.nih.gov/30098269/

some ways Keto help are not well understood
www.ncbi.nlm.nih.gov/pmc/articles/PMC5790787/

Curtis has a website
ketonesforparkinsons.com/

Could Fasting Help Control PD Symptoms?

This 2019 report in the National Library of Medicine (National Center for Biotechnology Information) looks at lifestyles and dietary habits associated with PD. A fasting mimicking diet (FMD), fasting 3 days followed by 4 days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting the involvement of BDNF in FMD-mediated neuroprotection. The findings showed that FMD also inhibited neuroinflammation and modulated the shifts in gut microbiota composition.

Source: Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites – PubMed

Interaction of Mitochondria, a-Syn, and the Endo-lysosomal System

A 2019 study published in the International Journal of Molecular Sciences looked at the interaction of mitochondria, a-synuclein and the endo-lysosomal system. PD is characterized by dopaminergic neuronal loss and the alpha-synuclein-containing Lewy body inclusions in the substantia nigra. Genetic investigations have revealed evidence of the involvement of mitochondrial function, alpha-synuclein (α-syn) aggregation, and the endo-lysosomal system, in disease pathogenesis. Although familial parkinsonism makes up less than 10% of adult parkinsonism, the findings generated from genetic studies have enhanced the understanding of the neuron degeneration processes. These include mitochondrial dysfunction, disruption of network integrity, and α-syn accumulation; the functions of the proteasome and endo-lysosomal pathways in cellular degradation. Mitochondrial dysfunctions, endo-lysosomal disruptions, and α-syn aggregation mutually interact within neurons, while α-syn prion-like propagation may also be associated with PD in an inter-neuronal manner. Both mitochondria and endo-lysosomal dysfunction contribute to the development of α-syn pathology, however, the specific organelle playing the most important role might be decided by genetic and environmental factors. Most likely, a vicious cycle may develop once one system becomes dysfunctional. Further elucidation of the precise molecular mechanisms involved in the pathogenesis of PD may lead to the development of future therapeutic targets to treat PD.

Source: The Overcrowded Crossroads: Mitochondria, Alpha-Synuclein, and the Endo-Lysosomal System Interaction in Parkinson’s Disease

Could α-Synuclein Inhibition be a Treatment for PD?

A 2020 publication in the MDPI journal, Biomolecules looks at targeting a-syn for PD therapeutics. PD is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy Bodies (cytoplasmic inclusions). The Lewy Bodies are clumps of protein that can build up and create problems in the brain. The Lewy Bodies contain the aggregated a-synuclein protein that can propagate throughout the brain. Many PD studies have looked at ways of inhibiting a-synuclein accumulation to ease PD symptoms. There are various approaches to a-syn inhibition and multiple clinical trials that examine the link between PD and a-syn, with the hope that a treatment may be found for PD using a-syn. Given the central role of α-syn in PD pathology and progression, α-syn met the criteria to be a tantalizing and evident therapeutic target for PD. Promising strategies include predominantly immunization, anti-aggregative molecules, and an increase in α-syn clearance.

Source: Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

Ridding Cells of Harmful Protein Aggregates by Inducing Autophagy

This short, enlightening video clip is an extract from a FoundMyFitness interview with Dr. Guido Kroemer. PD is characterized by protein aggregation of a-synuclein and mitochondrial dysfunction, partly due to mitophagy failure. A recently proposed strategy in preventing (or perhaps treating) neurodegenerative diseases like PD is to starve the cells or use biochemical methods to induce general autophagy and thus help the cell rid itself of protein aggregates. Here Dr. Kroemer describes how mitophagy contributes to the pathophysiology of neurodegenerative diseases like PD and Alzheimer’s and how autophagy might mitigate these processes.

Can RYR supplements Potentially be Related to a High Risk of PD?

Red yeast rice (RYR or red Koji) is an ingredient in dietary supplements often used for people with dyslipidemia or with statin-intolerance. These supplements contain monacolin K (lovastatin). This 2017 study published by NCBI made a case-by-case assessment highlighting myopathies and liver injury as potential safety issues, thus suggesting that the safety profile of RYR is similar to statins. RYR is used in Chinese medicine as a natural statin to improves blood circulation by decreasing cholesterol and triglyceride levels. Certain studies have shown that statin use and a higher risk of PD are related and that PD symptoms appear to be stronger following use of statins. These findings raise the hypothesis that the safety profile of RYR is highly similar to that of synthetic statins and warrants further investigation to finally characterize the safety profile of RYR. The conclusion of this report is that the safety profile of RYR is similar to that of statins and the risk profile of these supplements needs to be examined and regulated.

Source: Adverse reactions to dietary supplements containing red yeast rice: assessment of cases from the Italian surveillance system

Neuronal Autophagy and the Predisposition for PD

A study by Dr. Yue published by the Michal J. Fox Foundation tested the hypothesis that neuronal autophagy is critical for the regulation of alpha-synuclein protein levels and protective against neuronal death; dysfunction of autophagy predisposes to the pathogenesis of PD in dopamine neurons. This was done by establishing conditional knock-out mice in which an essential autophagy gene, Atg7, is deleted specifically in dopamine neurons. These pre-clinical models were used to investigate whether alpha-synuclein wildtype or PD-mutant A53T will be accumulated and deposited into Lewy body-like inclusions in the mutant dopamine neurons. In addition, they studied the effect of inactivation of autophagy on oxidative stress level, striatal dopamine content, and dopamine neuron degeneration. results suggest that neuronal autophagy is critical for the regulation of alpha-synuclein protein levels and protective against neuronal death; dysfunction of autophagy may predispose dopamine neuron to PD-like pathology.

Source: Autophagy in Dopamine Neurons: Clearance of Alpha-synuclein and Neuroprotection

PD and Autophagy Impairment in Synucleinopathy

A 2019 study published by NCBI discusses the active participation of autophagy impairment in alpha-synuclein accumulation and propagation, as well as alpha-synuclein-independent neurodegenerative processes in the field of synucleinopathy. There is genetic and post-mortem evidence suggesting that autophagy is involved in synucleinopathies. Also, studies demonstrate the role of autophagy in the pathology of synucleinopathy. α-syn is mainly degraded by both macroautophagy and chaperone-mediated autophagy. Thus, autophagy defects induce intracellular α-syn accumulation, participating in its aggregative state towards the formation of α-syn-positive intracytoplasmic inclusions. Plus, autophagy defects also increase the α-syn secretion by the non-autophagic exosomal pathway, leading to increased cell-to-cell transmission of the protein, and thus the propagation of the α-syn-linked pathology in different brain regions of the CNS. However, autophagy defects also cause detriment effects in cellular homeostasis: (i) lysosomal impairment through structural or functional defects leads to accumulation of non-degraded products and increased production of ROS; (ii) decreased mitophagy leads to neuronal bioenergetic imbalance, and (iii) defective cargo trafficking impairs the addressing of vesicles to lysosomal clearance. There is increasing evidence that inducing the autophagy pathways (by natural, chemical, or genetic approaches), has become a relevant therapeutic approach to counteract the deleterious effects of autophagy impairment in synucleinopathy.

Source: Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery

Prebiotics to prevent and treat constipation

This 2020 NCBI meta-analysis takes a close look at prebiotics which play a role in augmenting the presence of gut microbiota such as Bifidobacterium, Clostridium, Bacteroidetes, and Lactobacilli which have been demonstrated in functional gastrointestinal disorders. There are only a few studies of the efficacy of prebiotics for chronic constipation and the utility of different commercially available prebiotics in patients with functional and chronic idiopathic constipation. 21 randomized controlled trials were reviewed showing prebiotics to be effective treatments for chronic idiopathic constipation; improvement in stool consistency; the number of bowel moments, and bloating.

Source: Therapeutic Effects of Prebiotics in Constipation: A Review – PubMed

What is the Potential of Stem Cell Treatment for PD? (YouTube Webinar)

This webinar is a recording of a live broadcast that took place in June 2019 and consisted of a panel discussion on cell-based therapy for PD. Chairing the panel is Professor Patrik Brundin. The panel of experts includes Gaynor Edwards, a person affected by PD; Parkinson’s neurologist, Clair Henchcliffe and Dr. Roger Barker, consultant neurologist. The panel discusses what kind of stem-cells exist; the source of stem-cells; the uses of stem-cells, and specifically dopamine stem-cells. The panel talks about current trials and the timeline for when stem-cells will be a viable treatment for PD. One of the issues raised is whether we will be able to produce stem-cells in large enough quantities. The panel of experts takes questions from viewers and gives answers on subjects like stem-cell tourist and the cost of treatment. The final word on the subject is that despite the cost of potential stem-cell treatment it will save money spent on the medical care of untreated patients in the long term.

Could Coenzyme Q10 be Used as a Supplement for PD Patients?

A paper by Robert Alan Bonakdar, MD, and Erminia Guarneri MD, published by aafp.org in 2005 looks at coenzyme Q10 and its use in the treatment of a variety of disorders including PD, plus cardiac, immunologic, and oncologic conditions. Coenzyme Q10 appears to be a safe supplement with minimal side effects and low drug interaction potential. As yet, coenzyme Q10 has not been approved for the treatment of specific diseases in the USA. A randomized, double-blind, placebo-controlled, multicenter study of 80 patients found that 1,200 mg per day of coenzyme Q10 was associated with up to 44 percent less functional decline in patients with Parkinson’s disease, including activities of daily living. A study of 28 patients with Parkinson’s disease also demonstrated mild symptom improvement with daily oral dosing of 360 mg of coenzyme Q10. These results are awaiting confirmation.

Source: Coenzyme Q10 – American Family Physician

Initial Pramipexole vs. Initial Levodopa in Early PD – Which is Better?

A study published on the JAMA Network focused on the long-term effect of initiating pramipexole vs levodopa in early PD. The subjects were followed for up to two years and after six years. Disability was assessed using the modified Shwab and England Activities of Daily Living Scale. Other factors that were assessed included daytime sleepiness; disease severity; dopaminergic events; edema; depression; cognitive impairment and quality of life. Self-reported results were similar. Dopaminergic motor complications were more common in the initial levodopa group (68.4%) although disabling dyskinesias were uncommon in both groups. The mean (SD) Epworth Sleepiness Scale score was significantly higher in the initial pramipexole group. Mean (SD) changes from baseline in the total Unified Parkinson’s Disease Rating Scale score did not significantly differ. The study concluded that persistent differences favoring initial pramipexole were seen in the rates of dopaminergic motor complications, with less severe somnolence favoring initial levodopa.

Source: Long-term Effect of Initiating Pramipexole vs Levodopa in Early Parkinson Disease | Movement Disorders | JAMA Neurology | JAMA Network

Should Pramipexole be Used in PD Treatment?

A 2003 study published on Springer.com looked at pramipexole in comparison with I-dopa. The study subjects were twenty right-handed patients with early or mild PD. They were evaluated using neuropsychological and clinical assessments during three treatment modalities. 1. When in the off treatment condition; 2. When on pramipexole and 3. When on i-dopa. In comparison to the off treatment condition, the DA-agonist pramipexole produced a significant impairment of short term verbal memory, attentional-executive functions, and verbal fluency, while l-dopa did not. Pramipexole opposite to l-dopa, failed to improve FAS and Stroop tests. Pramipexole may worsen cognitive functions although not exceeding normative values.

Source: Pramipexole in comparison to l-dopa: a neuropsychological study | SpringerLink

Potential PD Treatment with Repurposed Drugs

A 2018 Springer article examines drug repurposing in PD due to the ever-increasing costs and lengthy processes for drug development. Existing compounds are being approved for other indications as novel treatments in PD. Advances in rational and systemic drug repurposing have identified a number of drugs with potential benefits for PD pathology and offer a potentially quicker route to drug discovery. Among the drugs being considered for repurposing for PD are ambroxol; isradipine; Inosine; ursodeoxycholic acid; deferiprone; exenatide; Nilotinib and Simvastatin. Despite the potential advantages offered by drug repurposing, as a strategy, it offers unique challenges, including the unavoidable need for expensive and risky clinical trials to demonstrate safety and efficacy in a new population while the limited patent protection often means a lack of commercial interest or incentive for further investment.

Source: Drug Repurposing in Parkinson’s Disease

The Potential of Ambroxol for PD Treatment

Dr. Stephen Mullin of the University of Plymouth talks for The Cure Parkinson’s Trust about the research into GBA Parkinson’s and the current convergent studies which all seem to be pointing towards GBA. In terms of the prospects to develop drugs to slow the development of PD, GBA is the most advanced. The next phase will be identifying PD patients who are carriers of the mutations in the GBA gene and beginning clinical human trials. Simultaneously there needs to be research into how GBA causes PD in humans. The prospects for ambroxol as a disease modifying agent in GBA PD are strong. Ambroxol has already been used by many patients and may be able to reverse some of the effects that lead to PD.

Source: The Ambroxol Trial – The facts | The Cure Parkinson’s Trust

Low‐Fat vs Ketogenic Diet for PD?

A 2018 study published in NCBI  aimed to compare the plausibility, safety, and efficacy of a low‐fat, high‐carbohydrate diet versus a ketogenic diet in PD patients. Primary outcomes were within‐ and between‐group changes in MDS‐UPDRS Parts 1 to 4 over 8 weeks. 47 patients were randomized, of which 44 commenced the diets and 38 completed the study (86% completion rate for patients commencing the diets). The ketogenic diet group maintained physiological ketosis. Both groups significantly decreased their MDS‐UPDRS scores, but the ketogenic group decreased more in Part 1 (−4.58 ± 2.17 points, representing a 41% improvement in baseline Part 1 scores) compared to the low‐fat group (−0.99 ± 3.63 points, representing an 11% improvement) (P < 0.001), with the largest between‐group decreases observed for urinary problems, pain and other sensations, fatigue, daytime sleepiness, and cognitive impairment. The trial found that It is plausible and safe for PD patients to maintain a low‐fat or ketogenic diet for 8 weeks. Both diet groups significantly improved in motor and nonmotor symptoms; however, the ketogenic group showed greater improvements in nonmotor symptoms.

Source: Low‐fat versus ketogenic diet in Parkinson’s disease: A pilot randomized controlled trial (© 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

 

Health Solutions Library for Critical Diseases Including PD

If you’re dealing with a chronic disease or you know someone who is then Chris Kresser’s Health Solutions Library can provide you with resources. Among the resources are books and ebooks that cover preventing and reversing chronic illness and guides for living a healthier life. There are also courses you can take in health care and articles focused on health written by leading specialists. Kresser offers an easy-to-use index to help you find the resources for your particular ailment.

Source: Health Solutions Library | Chris Kresser