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Breakthrough in Early Detection and Treatment of Parkinson’s Disease

Breakthrough in Early Detection and Treatment of Parkinson’s Disease

June,5,2019

Israeli researchers devise microscopic technique that can detect earliest symptoms of degenerative disorder

Israeli researchers, in conjunction with peers in Germany and the United Kingdom, have developed a new method to detect the earliest signs of Parkinson’s disease and, therefore, potentially delay its progression. The discovery could enable scientists to treat the neurodegenerative disorder in its infancy and track the evolution of symptoms.

Parkinson’s, which has no known cure, affects nerve cells in the brain that are responsible for producing dopamine. It leads to tremors as well as changes in cognition, speech and gait, among others. An estimated 10 million people suffer from the disease worldwide.

Scientists from Tel Aviv University – in collaboration with researchers at the Max Planck Institute and Cambridge University – were primarily responsible for the discovery of a process that identifies the aggregation of the alpha-synuclein protein, which is a hallmark of the Parkinson’s.

“Until now, you could detect this aggregate usually at the post-mortem stage via brain biopsies or something invasive,” Professor Uri Ashery, co-author of the study and head of Tel Aviv University’s Sagol School of Neuroscience, told The Media Line. “It is possible to treat the accumulation at early stages but in the past we wouldn’t have known about it, so it’s very important to be able to detect this [as soon as possible].”

Ashery said that scientists used special microscopes to spot changes in the quantity of alpha-synuclein proteins in mice.

“We took samples from mice brains… [and] found that we really can detect the aggregation process and define the bio-markers that represent the development of the disease,” Ashery elaborated. He emphasized that these bio-markers were different from those that are already identifiable in the later stages of Parkinson’s.

Thanks to the new Israeli discovery, researchers were able to study the effects of the drug anle138b, which was created by members of the Max Planck Institute to treat the disorder.

“There was a recovery in motor function [and an increase in] dopamine release, so everything was very positive,” Ashery stressed, adding that the next step is to develop a non-invasive way to implement the breakthrough detection method on humans.

Dr. Dana Bar-On of Tel Aviv University’s Sagol School of Neuroscience, another co-author of the study, told The Media Line that the project started four years ago and is ongoing.

“The earlier you treat the more effective [it will be] because with Parkinson’s there is a great problem. Symptoms appear when 80 percent of the dopaminergic cells in the patient’s brain are already dead, so it’s too late,” Bar-On explained.

“So it is our belief,” she continued, “that we can use this new method, for example on relatives of Parkinson’s patients. The microscopy enables you to see [the disorder]…from a very early stage because of the resolution. It can already track a single protein.”

Bar-On further noted that researchers at Cambridge University developed a unique transgenic mouse that contracted the disease spontaneously. Its appearance in mice was previously almost always a function of mutations, she said, thus “the new model is more reflective of the situation of Parkinson’s, which is not all genetic.”

It is Bar-On’s hope that in the future doctors will be able to use the Israeli detection method to diagnose early-stage Parkinson’s, possibly by taking biopsies from the skin or the gut.

Click here for the original article from The Medialine website

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Parkinson’s Disease Vaccine Shows Preclinical Promise

Parkinson’s Disease Vaccine Shows Preclinical Promise

Date: Nov 15, 2018

The biotech company United Neuroscience has developed a candidate Parkinson’s disease vaccine that targets a protein linked to the condition.

The vaccine teaches the immune system to attack aggregations of alpha-synuclein. When this protein aggregates in neurons, it can lead to several neurodegenerative disorders, including Parkinson’s.

In United Neuroscience’s preclinical study, the vaccine was able to prevent the protein from aggregating in cell cultures, in mice and in post-mortem brain tissue of patients with Parkinson’s, Lewy body dementia and multiple system atrophy.

The company, headquartered in Dublin, has not specified when the vaccine might go to the clinic. As alpha-synuclein is involved in other diseases such as Lewy body dementia and multiple system atrophy, this vaccine could target several diseases in the clinic.

United Neuroscience has used the same platform to make a vaccine against Alzheimer’s disease, which is currently being tested in Phase II, with results expected at the end of this year.

There are companies that have Parkinson’s immunotherapies in the clinic already. Earlier this year, Affiris, an Austrian biotech, reported good safety results for its own alpha-synuclein vaccine in 24 patients in Phase I. Another Irish company, Prothena, in partnership with Roche, is running a Phase II trial with a different approach: injecting alpha-synuclein antibodies directly into patients.

 Click here for the original article from Parkinson’s Disease Vaccine website

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World-first pill may stop Parkinson’s

World-first pill may stop Parkinson’s

A new therapy that appears to stop Parkinson’s disease “in its tracks” will begin phase-one clinical trials in humans next year.

The therapy, developed by researchers at the University of Queensland – and partly under-written by the Michael J Fox Foundation – is a world first because it stops the death of brain cells in Parkinson’s sufferers rather than managing symptoms.

If human trials echo the stunning results in animal testing, the inflammation of the brain that causes so much of the progressive damage in Parkinson’s disease (PD) could be halted by taking a single pill each day.

UQ Faculty of Medicine researcher Associate Professor Trent Woodruff said the key to the new therapy is a small molecule, MCC950 – a compound developed and abandoned 10 years ago by a big pharma company that didn’t understand how it actually worked.

At that stage, though, inflammation in the Parkinson’s brain was less well understood.

Parkinson’s disease, said Dr Woodruff, is characterised by the loss of brain cells that produce dopamine, a chemical that co-ordinates motor control – and it’s the loss of dopamine that has been the focus of treatment. But it is also accompanied by this chronic inflammation that occurs as an immune response gone haywire.

It works like this: Inflammation is activated in our cells by complex proteins called inflammasomes. About five years ago, Dr Woodruff and his team found that the immune system causes the NLRP3 inflammasome to light up in Parkinson’s patients, with signals found in the brain and even in the blood.

They then found that the tiny molecule MCC950, given orally once a day, in experiments with mice, “blocked NLRP3 activation in the brain and prevented the loss of brain cells, resulting in markedly improved motor function”.

UQ Institute for Molecular Bioscience researcher Professor Matt Cooper – who initially experimented with MCC950 in the treatment of an auto-inflammatory disease called Muckle-Wells syndrome that can cause deafness and kidney failure – said drug companies had traditionally tried to treat neurodegenerative disorders by blocking neurotoxic proteins that build up in the brain and cause disease.

“We have taken an alternative approach by focusing on immune cells in the brain called microglia that can clear these toxic proteins,” he said.

“With diseases of ageing such as Parkinson’s, our immune system can become over-activated, with microglia causing inflammation and damage to the brain.”

He said MCC950 effectively “cooled the brains on fire”, turning down microglial inflammatory activity, and allowing neurones to function normally.

This was achieved with three different models of Parkinson’s on mice. It took a further two years of tests in order to convince the editors of the prestigious journal Science Translational Medicine of the efficacy of treatment. The researchers’ paper was published on October 31.

The progress of MCC950 to market appears to be happening rather quickly. Both the Michael J Fox Foundation for Parkinson’s Research and the Ireland-based drug company Inflazome are keen for human trials to start as soon as possible.

Dr Woodruff said much of the preclinical work was already completed.

The biggest hurdle, apart from funding, is that MCC950 came off a patent. This means the researchers have had to develop variations of the original drug for intellectual property reasons. Those new drugs are currently being tested and, according to Dr Woodruff, proving to be even more effective.

There are 10 million people with Parkinson’s disease worldwide. They still have a few years to wait and see if the magic in the lab can be replicated in people.

The phase-one tests next year will determine whether or not the drug is safe in healthy people. All going well, volunteers with Parkinson’s will be recruited for phase-two testing in 2020.

Whether Michael J Fox himself will be one of those volunteers is not yet known.

 Click here for the original article from pill may stop Parkinson’s website

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Kyoto University to begin iPS clinical test for Parkinson’s disease

Kyoto University to begin iPS clinical test for Parkinson’s disease

July 30, 2018
A Kyoto University research team said Monday it will begin a clinical test this week using induced pluripotent stem cells to treat Parkinson’s disease, in what will be the world’s first application of iPS to the progressive neurological disorder.

The team led by Jun Takahashi, a professor at the university’s Center for iPS Cell Research and Application, has received government approval and is soliciting seven patients to participate in the trial to be conducted at Kyoto University Hospital.

The research team said one of the patients taking part in the study will be selected from those currently being treated at Kyoto University Hospital.

The researchers are aiming to develop the method as a new treatment covered by national health insurance.

While some experts call for careful application due to concerns that such iPS cells could turn into malignant tumors, Takahashi said at a press conference the trial could provide patients with a “promising choice of treatment.”

Parkinson’s disease reduces dopamine-producing neurons in the brain and results in tremors in the hands and feet, and stiffness in the body. While there are treatments to relieve the symptoms, there is currently no cure for the disease.

In the clinical test that will start on Wednesday, nerve cells derived from other people and stored at the university will be transplanted into the brains of patients to supplement damaged nerve cells.

The nerve cells are created using cells from people who have types of immunity that make them less prone to transplant rejections.

The team has already tested the process on monkeys in a preclinical study, in which the movement of the affected animals improved without seeing any tumors that could develop into cancer in the brain over a two-year observation period.

In Japan, an estimated 160,000 people suffer from Parkinson’s disease. Many patients develop symptoms in their 50s or older, and the number of patients is rising due to the aging of society.

Kosei Hasegawa, representative chairman of the Japan Parkinson’s Disease Association, said patients have huge expectations of the iPS therapy.

Hasegawa said many people are hoping to join the clinical research, adding, “I want the method to be established as a treatment available for anyone as soon as possible.”

In one of the currently available treatments, electrodes are placed inside the brain to send electric signals and alleviate symptoms, even though it is not effective for all patients.

A woman who was diagnosed with Parkinson’s disease more than 10 years ago said, “If iPS treatment is established, it will offer more choices for patients with progressed symptoms,” she said.

Among other clinical tests of iPS cells, the government-backed Riken institute conducted the world’s first transplant of retinal cells grown from iPS cells to a patient suffering from a serious disease in 2014.

IPS cells can grow into any type of body tissue and are seen as a promising tool for regenerative medicine and drug development. Shinya Yamanaka, who heads the iPS center, won the Nobel Prize in physiology or medicine in 2012 for discovering iPS cells.

 

 Click here for the original article from iPS clinical test for Parkinson’s disease website

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