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Parkinson’s Breakthrough August 2021

Research Breakthrough Will Help Develop Future Treatments Against Parkinsons Disease

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Researchers from the University of Dundee have discovered a small molecule that helps to eliminate a Parkinsons disease-causing protein

Researchers from the University of Dundee have discovered a small molecule that helps to eliminate a Parkinsons disease-causing protein.

Parkinsons disease is a progressive neurodegenerative disorder affecting more than 10 million people worldwide. No cure is available and current treatment is limited to symptomatic management.

Researchers from the Universitys Centre for Targeted Protein Degradation and MRC Protein Phosphorylation and Ubiquitylation Unit have made significant strides towards developing new therapies through the design of XL01126, a small molecule that degrades a protein known to play a key role in the development of Parkinsons.

The protein, Leucine Rich Repeat Kinase 2 , is one of the most important and promising targets for developing treatments for Parkinsons disease, but until now scientists have only been able to inhibit its function rather than destroying it completely.

XL01126 eliminates LRRK2 from within the cell by utilising the cells natural waste disposal system. The research also demonstrated that XL01126 can be taken orally and can be detected in the brain in mice, two sought-after features of drugs targeting neurodegenerative diseases that can be very challenging to achieve.

The article is available and open access here:

Artificial Intelligence Model Can Detect Parkinsons From Breathing Patterns

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Parkinsons disease is notoriously difficult to diagnose as it relies primarily on the appearance of motor symptoms such as tremors, stiffness, and slowness, but these symptoms often appear several years after the disease onset. Now, Dina Katabi, the Thuan and Nicole Pham Professor in the Department of Electrical Engineering and Computer Science at MIT and principal investigator at MIT Jameel Clinic, and her team have developed an artificial intelligence model that can detect Parkinsons just from reading a persons breathing patterns.

The tool in question is a neural network, a series of connected algorithms that mimic the way a human brain works, capable of assessing whether someone has Parkinsons from their nocturnal breathing i.e., breathing patterns that occur while sleeping. The neural network, which was trained by MIT PhD student Yuzhe Yang and postdoc Yuan Yuan, is also able to discern the severity of someones Parkinsons disease and track the progression of their disease over time.

Over the years, researchers have investigated the potential of detecting Parkinsons using cerebrospinal fluid and neuroimaging, but such methods are invasive, costly, and require access to specialized medical centers, making them unsuitable for frequent testing that could otherwise provide early diagnosis or continuous tracking of disease progression.

New Protocols Extend Therapeutic Benefits Of Deep Brain Stimulation

Date:
Carnegie Mellon University
Summary:
Researchers have found a way to make deep brain stimulation more precise, resulting in therapeutic effects that outlast what is currently available. The work will significantly advance the study of Parkinsons disease.

Researchers from Carnegie Mellon University have found a way to make deep brain stimulation more precise, resulting in therapeutic effects that outlast what is currently available. The work, led by Aryn Gittis and colleagues in CMUs Gittis Lab, will significantly advance the study of Parkinsons disease.

DBS allows researchers and doctors to use thin electrodes implanted in the brain to send electrical signals to the part of the brain that controls movement. It is a proven way to help control unwanted movement in the body, but patients must receive continuous electrical stimulation to get relief from their symptoms. If the stimulator is turned off, the symptoms return immediately.

Gittis, an associate professor of biological sciences in the Mellon College of Science and faculty in theNeuroscience Institute, said that the new research could change that.

By finding a way to intervene that has long-lasting effects, our hope is to greatly reduce stimulation time, therefore minimizing side effects and prolonging battery life of implants.

Teresa Spix, the first author of the paper, said that while there are many strong theories, scientists do not yet fully understand why DBS works.

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Amneal Tests A New Formulation

AmnealPharmaceuticals plans to report Phase III safety results for IPX-203, a reformulation of the common generic PD treatment combination of carbidopa and levodopa that could reduce symptom fluctuations. The company said the Phase III, open-label extension study will have results available by the end of the second quarter of 2022.

CD/LD can lead to troughs and spikes of plasma levels that generate side-effects like dyskinesia, Kordower explains. A new extended-release version of CD/LD could smooth out these drops, he notes.

If approved, IPX-203 will join several other marketed reformulations of CD/LD. Amneals own extended-release capsule Rytary, Schwarz Pharmas orally disintegrating tablet Parcopa, and AbbVies enteral suspension Duopa all have FDA approval in PD. A GlobalData consensus forecasts pegs peak IPX-203 sales at $127 million in 2028.

In a separate, placebo-controlled Phase III trial , IPX-203 resulted in 0.53 more hours of ON time than immediate-release CD/LD after seven weeks . Earlier, a six-week Phase II trial of IPX-203 reported no serious treatment-emergent adverse events among the 26 patients enrolled. Experts say the long-term safety data will be key in determining IPX-203s place among CD/LD formulations.

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Over The Counter & Complementary Therapies

Parkinson

People with Parkinsons who seek relief from their symptoms may decide to explore complementary therapies, which can support or complement traditional medicine. While there are many kinds of complementary medicine, this section focuses on herbs, vitamins and supplements.

Page reviewed by Dr. Chauncey Spears, Clinical Assistant Professor and Dr. Amelia Heston, Movement Disorders Fellow at the University of Michigan.

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What Are Mesenchymal Stem Cells

Stem cells are the body’s raw materials â cells from which all other cells with specialized functions are created. Mesenchymal stem cells are adult stem cells that have self-renewal, immunomodulatory, anti-inflammatory, signaling, and differentiation properties. Mesenchymal stem cells , self renewal capacity is characterized by their ability to divide and develop into multiple specialized cell types present in a specific tissue or organ.

Mesenchymal stem cells can be sourced from a variety of tissue including adipose tissue , bone marrow, umbilical cord tissue, blood, liver, dental pulp, and skin.

MSCs are widely used in the treatment of various diseases due to their self-renewable, differentiation, anti-inflammatory, and immunomodulatory properties. In-vitro and in-vivo studies have supported the understanding mechanisms, safety, and efficacy of MSC therapy in clinical applications.

Trials Registered On Clinicaltrialsgov

To allow for a comparison with our 2020 report, we initially focused our analysis on just the trials registered on clinicaltrials.gov. Table 1 displays the classification of the clinicaltrials.gov trials by ST and DMT compared to our analysis from 2020 . There has not been a major change in the numbers of trials listed on clinicaltrials.gov, nor in the distribution across phases. The 2021 review contains 83 ST trials, compared to 88 in 2020 with a slightly higher number of DMT trials , a total of 142 vs 145 in 2020. There has, however, been considerable change in the mix of trials, with 45 studies dropping off the list, of which 25 were completed, 4 terminated, 2 withdrawn and 14 moved to unknown status. While these studies were removed, 42 new trials have been added to the list.

Table 1

*clinicaltrials.gov numbers only.

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Exploring Seven Recently Approved Parkinsons Treatments

Remarkably, in the last five years, seven new medications have been approved for the treatment of the motor symptoms of Parkinsons disease , with two approved in 2020. Thats exciting progress! And while it is great to have so many choices, the various options can be confusing so today I will describe these new medications and their uses.

Blood Biomarkers Identified For Cognitive Changes With Parkinsons

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Blood levels of small vesicles originating in neurons and containing proteins related to Parkinsons disease or Alzheimers disease alpha-synuclein, phosphorylated tau, or insulin receptor substrate 1 can be biomarkers of cognitive impairment in Parkinsons patients, a study reported. Changes in the levels of vesicles carrying these

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Could Low Frequency Dbs Improve Gait In People With Parkinsons

Deep brain stimulation is a surgical procedure in which electrodes are implanted inside the brain to help ease symptoms of the condition. However, for some people, standard DBS treatment can lead to postural instability which can cause trouble with balance while walking.

In a recent small clinical trial, researchers in Australia assessed whether low-frequency DBS could help improve balance problems in people with Parkinsons. The team reported findings for 14 participants who were treated with both standard high-frequency DBS and low-frequency DBS. After each treatment, the participants took part in walking assessments while wearing specialised sensors.

Using the data collected from these sensors, the team analysed the participants walking ability and found that low-frequency DBS led to significant improvements in rhythmic movements compared to high-frequency stimulation.

These findings provide evidence for the potential utility of low-frequency stimulation parameters for post-operative patients who experience gait complications, the researchers wrote. But, they added: It is noteworthy that the low-frequency stimulation strategy was not tolerated by all participants and, in some cases, the gait improvements came at the cost of a re-emergence of tremor.

Read more:

Parkinsons Foundation Seeks To Add To Global Care Network In Us

To help expand patient access to treatments and other services, the Parkinsons Foundation is inviting U.S. medical centers that provide outstanding Parkinsons disease clinical care and resources to apply for membership in its Global Care Network. The network comprises Parkinsons Foundation Centers of Excellence as well as

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Gum Disease May Be Linked To Increased Risk Of Parkinsons

Researchers in South Korea have found that periodontitis, or gum disease, may increase the risk of Parkinsons disease.

As part of the study, the researchers used a population-based database to analyse data from 6,825,684 people over a period of eight years. The results showed that those with mild periodontitis had a 7.6% to 9.5% higher risk of developing Parkinsons disease.

The link between periodontitis and Parkinsons persisted even after the researchers factored in key health and lifestyle factors such as age, sex, BMI, level of income, other medical conditions and smoking, drinking and exercise habits. People with periodontitis and metabolic syndrome a combination of diabetes, high blood pressure and obesity were found to have a 16.7% higher risk of Parkinsons than those without the two conditions.

Reflecting on these results, the study authors concluded: Treatment and prevention of periodontal diseases may benefit systemic health.

Innovative Gel Offers New Hope To Defeat Parkinson’s Disease

Parkinson

When we introduced the gel technology with the stem cells we saw huge improvement in the animals’ coordinated paw movement and overall motor function recovery.

Researchers from The Australian National University , in collaboration with The Florey Institute of Neuroscience and Mental Health, have developed a new type of hydrogel that could radically transform how we treat Parkinson’s disease. The gel also offers hope for patients who have suffered from other neurological conditions such as strokes.

The new material is made from natural amino acids – the building blocks of proteins – and acts as a gateway to facilitate the safe transfer of stem cells into the brain and restore damaged tissue by releasing a growth-enabling protein called GDNF.

The research has been published in the journal Advanced Functional Materials.

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The First Participant Has Been Recruited To A Pioneering Clinical Trial Which Is Testing A New Drug Called Nlx

Parkinsons disease is a condition in which parts of the brain become progressively damaged over many years. The main three symptoms manifest themselves in involuntary shaking of parts of the body, slow movement, and stiff, inflexible muscles.

People with Parkinsons struggle to make enough dopamine. They take medications like levodopa which help their struggling dopamine cells to make more of this chemical and helps improve symptoms, especially difficulty in movement.

However, serotonin cells also get involved in using levodopa to make and release dopamine, but they do so in an erratic manner. This uncontrolled release of dopamine leads to distressing uncontrollable movements called dyskinesia.

The trial is led by researchers at the Karolinska Institute in Stockholm and at 4 other sites in Sweden. A total of 24 participants will be involved, with 16 receiving NLX-112 and the remainder an inactive pill for comparison.

Component #3 Some Form Of Restorative Therapy

Once the condition has been slowed/halted and a neuroprotective/nurturing environment is in place to protect the remaining cells , a curative treatment for Parkinsons will require replacing some of the cells that have been lost.

And until we have developed methods that can identify Parkinsons long before the motor features appear , some form of cell replacement therapy is required to introduce new cells to take up lost function.Cell transplantation currently represents the most straight forward method of cell replacement therapy.

Cell Transplantation

Traditionally, the cell transplantation procedure for Parkinsons has involved multiple injections of developing dopamine neurons being made into an area of the brain called the putamen . These multiple sites allow for the transplanted cells to produce dopamine in the entire extent of the putamen. And ideally, the cells should remain localised to the putamen, so that they are not producing dopamine in areas of the brain where it is not desired .

Targeting transplants into the putamen. Source: Intechopen

Transplanted dopamine neurons. Source: Sciencedirect

The transplanted cells take several years to develop into mature neurons after the transplantation surgery. This means that the actually benefits of the transplantation technique will not be apparent for some time . Once mature, however, it has also been demonstrated that these transplanted cells can produce dopamine.

Source: Fujifilm

Ok, thats it.

I think we are done.

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Parkinsons Disease Pipeline Offers Promising New Options For Treatment

DelveInsights Parkinsons Disease Pipeline Insight report provides comprehensive insights about 150+ companies and 150+ pipeline drugs in the Parkinsons Disease pipeline landscapes.

Los Angeles, USA, Jan. 17, 2022 Parkinsons Disease Pipeline Offers Promising New Options for Treatment | DelveInsight

DelveInsights Parkinsons Disease Pipeline Insight report provides comprehensive insights about 150+ companies and 150+ pipeline drugs in the Parkinsons Disease pipeline landscapes.

The report comprises Parkinsons Disease pipeline drug profiles, including clinical and non-clinical stage products. It also includes the Parkinsons Disease therapeutics assessment by product type, stage, route of administration, and molecule type and further highlights the inactive Parkinsons Disease pipeline products.

Get an overview of pipeline landscape @ Parkinsons Disease Clinical Trials Analysis

Parkinsons Disease is a progressive disorder caused by degeneration of nerve cells in the part of the brain called the substantia nigra, which controls movement.

· Combination· Mono/Combination

Key Questions regarding Current Parkinsons Disease Treatment Landscape and Emerging Therapies Answered in the Pipeline Report

What New Treatments Are Being Developed

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Thanks to the progress we’ve already made, there are many different treatments available for Parkinson’s. And today new treatments are being tested in clinical trials that have the potential to slow, stop or even reverse Parkinson’s.

These include:

  • Stem cell therapies. These aim to use healthy, living cells to replace or repair the damage in the brains of people with Parkinson’s.
  • Gene therapies. These use the power of genetics to reprogramme cells and change their behaviour to help them stay healthy and work better for longer.
  • Growth factors . These are naturally occurring molecules that support the growth, development and survival of brain cells.

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Projects In The Pipeline

A Phase I trial of Affitope PD01A, a compound developed by clinical-stage biotech AFFiRiS , demonstrated the vaccine candidates long-term safety, efficacy and tolerability. In the study, PD01A appeared to provide the longest benefit when administered as an initial shot followed by a booster.

In 2020, AFFiRiS announced it was preparing to advance PD01A into Phase II trials. This July, neurodegenerative disease-focused AC Immune acquired AFFiRiSs portfolio of therapeutics targeting alpha-synuclein, including the companys Parkinsons vaccine candidate.

AC Immune has said it will immediately launch clinical development of ACI-7104, the optimised formulation of PD01A, into an adaptive, biomarker-based Phase II study. The trial will evaluate an initial dose-response of ACI-7104, focusing on immunogenicity against a-syn and pathological a-syn species. The progression of motor and non-motor symptoms of Parkinsons disease will also be monitored, along with digital, imaging and fluid biomarkers.

Another Parkinsons vaccine candidate is UB312, a synthetic peptide-based vaccine developed by United Neuroscience , which recently merged with COVAXX to form biotech company Vaxxinity. UB312 is currently in Phase I trials to assess its safety, tolerability, and immunogenicity in healthy participants and in participants with Parkinsons disease. The study is expected to be completed in June 2022.

What Is Deep Brain Stimulation

A DBS device is essentially a pacemaker for the brain. It is implanted in the upper chest and wired to electrodes in the brain.

It sends electric signals to the parts of the brain responsible for movement to stabilise signals and reduce the symptoms of neurological diseases such as Parkinson’s disease.

Dr Silburn said the treatment was recommended for patients whose condition had deteriorated to the extent that medication no longer improved their quality of life.

“We take away the cardinal symptoms of Parkinson’s and we’re able to take the drugs right down if not stop them all together,” Dr Silburn said.

Treatment involves regular adjustments to the devices, which Dr Silburn said could be needed as regularly as every two weeks.

Abbott’s wireless technology connects specialists such as Dr Silburn with patients like Mr Couperthwaite, via an app installed on paired devices allowing adjustments to be made remotely from anywhere in the world.

“This is going to have a major impact for particularly regional Australians,” Dr Silburn said.

“It reduces the burden of care, whether you’re remote in the bush or an hour away in the car someone has to give up their time to bring you in.

“If you’re way out in the middle of Australia and something goes wrong, you need to have a Careflight, that could be completely eliminated.”

Parkinson’s Queensland data shows more than 18,500 people live with the disease in this state.

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