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Thursday, June 16, 2022
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When Will There Be A Cure For Parkinson’s

European Biotechs Fire Up Deals To Develop Parkinsons Treatments

When will there be a cure for Parkinson’s?

Last month, European biotechs Ipsen and AC Immune announced multi-million euro deals to acquire or license treatments for Parkinsons disease. For some experts, this increasing interest in the brain disease with the fastest growing prevalence is long overdue.

In July, Swiss company AC Immune bought assets and intellectual property for investigational Parkinsons vaccines valued at nearly 50M from Austrian firm Affiris. AC immune will immediately begin a phase II clinical study involving an optimized formulation of the most advanced acquired vaccine candidate, which targets alpha-synuclein, a protein whose accumulation in the brain is linked to Parkinsons.

In the same month, the UK-based Ipsen signed a deal potentially worth more than 300M for an exclusive, global license to a small molecule Parkinsons drug from Swedish IRLAB. The drug, called mesdopetam, is being assessed in phase IIb trials to treat involuntary movements that can be a side effect from a common Parkinsons disease treatment called levodopa. Ipsen is now taking on preparations for phase III investigational studies of the same drug.

Currently, there is no cure for Parkinsons. Treatments such as physiotherapy, medication, and, in some cases, surgery are only able to alleviate symptoms and maintain quality of life. Levodopa is one of the main Parkinsons treatments in use it increases the levels of dopamine in the brain to address the motor symptoms of Parkinsons.

Its Not Just One Condition There Are Multiple Types Of Parkinsons

Like cancer, we are starting to understand the importance of subtyping Parkinsons and developing tailored treatments that will be more successful than a one size fits all approach. Better understanding is coming from large scale studies that follow vast numbers of people with the condition over time. And we are starting to see how the subtypes of Parkinsons have different symptoms, progression rates and even different responses to medication.

To effectively treat Parkinsons, we probably need to tackle each of these subtypes differently, providing the right treatments and support to suit the individual and their form of Parkinsons. And this starts with understanding more about how we classify and identify these different types.

You can read more about research into personalised treatments in our recent blog Precision medicine for Parkinsons, how close are we?

How Close Are We To A Cure For Parkinsons

Saskia Mair of Parkinsons Lifeinterviews Sohini Chowdhury, Deputy CEO of the Michael J Fox Foundation.

How close do you think the scientific community is to finding a cure for Parkinsons?

Whenever I say the word cure, I kind of put it in quotes. I think its important to remember that a cure can mean different things to different people.

If youre able to improve the symptom management of the disease to an extent where having the disease has very little impact on your day to day life, that could be considered a cure.

If youre able to slow or halt the disease progression so that the moment you get diagnosed, it never progresses beyond that point but youre still taking a pill every day for the rest of your life, that could be a cure.

Theres a recognition now that Parkinsons is not one disease experience. It is a disease experience that is very variable, so we have to be open minded because a cure for one person could be very different than a cure for another person.

I think the fact that this is now accepted in the research community is a good thing for patients. Its not a one size fit all approach. We have finally understood that we need lots of different cures to fit the different patient experiences under the name Parkinsons disease.

In terms of how close we are is it tomorrow? Absolutely not. But theres so many resources, money, scientific knowledge, and brainpower across the world being put forth into this.

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How Is Parkinson’s Disease Diagnosed

There is no test that can prove that you have PD. The diagnosis is based on you having the typical symptoms . In the early stage of the disease, when symptoms are mild, it may be difficult for a doctor to say if you definitely have PD. As the symptoms gradually become worse, the diagnosis often becomes more clear.

PD is sometimes confused with other conditions. Some conditions can give ‘Parkinsonism’ features – that is, symptoms similar to PD but caused by other conditions. For example, some medicines used to treat other conditions can cause side-effects which resemble symptoms of PD. Some rare brain disorders can also cause similar symptoms.

Therefore, it is normal practice in the UK to be referred to a specialist if PD is suspected. The specialist will be used to diagnosing PD and ruling out other causes of the symptoms. They will usually be either a neurologist or a doctor specialising in elderly care. If there is still doubt about the diagnosis, sometimes a scan of the brain is carried out. This helps to differentiate PD from some other conditions that can cause Parkinsonism features. Other tests sometimes needed include blood tests and tests of your sense of smell.

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What Causes Parkinsons Disease

Having Parkinsons disease means losing nerve cells in the brain resulting in major changes or abnormal body movements.

To get into detail, the part of the brain called substantia nigra is affected when a person is diagnosed with Parkinsons disease.

This part of the brain is responsible for the movements of a person. When a person is losing nerve cells in the substantia nigra, the production of dopamine is affected.

Dopamine is a neurotransmitter that sends messages and coordinates with the different parts of the body that involves movement. It helps us with the ability to plan and think and is also responsible for the feeling of pleasure.

The bodys dopamine production lessens when nerve cells are lost, which affects the movements in a persons body.

According to a report by Parkinsons Foundation, there are no evident triggers or causes where this disease comes from. Some experts relate it with having a genetic history and others from environmental factors, but none of them points to be conclusive yet.

However, people over 60 years old are more likely to be affected since reports state a 2-4% risk compared to 1-2% of people below that age.

Even if there is no convincing evidence, the development of PD may be related to a severe shock that may be caused by a head injury, mental condition, surgical operation, or even severe mental stress.

A Busy Year Ahead For Parkinsons Disease

Parkinsons disease research has ended in numerous dead ends despite substantial efforts over many years. Recently, Biogen and Sanofi scrapped their Parkinsons candidates, cipanemab and venglustat respectively, owing to lack of efficacy, and a disease-modifying therapy has yet to materialise.

But the push to find drugs that help beyond reducing symptoms continues, and Evaluate Vantage has delved into the pipeline of projects in active late-stage clinical trials. This year is shaping up to be crucial for the field, with 10 studies expected to yield data or to complete in 2021.

One target that crops up multiple times is GLP-1 this approach, traditionally employed in type 2 diabetes, is also being tested in Alzheimers. Among other avenues of research, it is hoped that gene therapy could offer a one-time cure for Parkinsons.

Repurposing

Research has suggested that GLP-1 agonists have neuroprotective benefits, and several trials of marketed diabetes drugs, as well as new GLP-1-targeting projects, are under way in Parkinsons. Some of these studies are investigator sponsored, including the most advanced, a UCL-run phase III trial of Astrazenecas Bydureon called Exenatide-PD3.

In the meantime, data are expected from several phase II studies of GLP-1 agonists, including a trial of Novo Nordisk’s Victoza, being run by Cedars-Sinai Medical in collaboration with the Danish company and The Cure Parkinson’s Trust. That study is set to complete in September.

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How Is Parkinsons Disease Diagnosed

There are currently no specific tests that diagnose PD. The diagnosis is based on:

  • medical history and a neurological examination
  • blood and laboratory tests, to rule out other disorders that may be causing the symptoms
  • brain scans to rule out other disorders. However, computed tomography and magnetic resonance imaging brain scans of people with PD usually appear normal.

In rare cases, where people have a clearly inherited form of PD, researchers can test for known gene mutations as a way of determining an individuals risk of developing the disease. However, this genetic testing can have far-reaching implications and people should carefully consider whether they want to know the results of such tests.

Can Parkinsons Disease Be Prevented

Is there a cure for Parkinson’s disease? How is is treated?

Unfortunately, no. Parkinsons disease is long-term disease that worsens over time. Although there is no way to prevent or cure the disease , medications may significantly relieve your symptoms. In some patients especially those with later-stage disease, surgery to improve symptoms may be an option.

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Establishing Pd Research Priorities

The NINDS-organized Parkinsons Disease 2014: Advancing Research, Improving Lives conference brought together researchers, clinicians, patients, caregivers, and nonprofit organizations to develop 31 prioritized recommendations for research on PD. These recommendations are being implemented through investigator-initiated grants and several NINDS programs. NINDS and the NIHs National Institute of Environmental Health Sciences held the Parkinsons Disease: Understanding the Environment and Gene Connection workshop to identify priorities for advancing research on environmental contributors to PD.

Research recommendations for Lewy Body Dementia, including Parkinsons disease dementia, were updated during the NIH Alzheimers Disease-Related Dementias Summit 2019 .

It Affects Everyone Differently

Yale Medicine does point out that not everyone experiences debilitating symptoms immediately. “It’s important to note that Parkinson’s disease manifests itself differently in each patient,” they explain. “Some people will be able to continue working and enjoy regular hobbies for many years after diagnosis, while others will have more severe symptoms that require major lifestyle adjustments.”

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There Isnt Enough Investment In Parkinsons

Over that last few decades there have been a number of large scale clinical trials for Parkinsons that have failed at the final hurdle. These disappointments have led some companies to redirect their investment into other research areas, which may be perceived to be lower risk and potentially more profitable. Without investment promising ideas start to pile up on shelves with no opportunity to move forward, and progression towards better treatments slows and eventually stalls.

There are promising scientific discoveries for Parkinsons that are not being picked up and developed by commercial companies. We believe we can step in here to bring new treatments forward faster. Through our Parkinsons Virtual Biotech were acting in a similar way to a small biotech company. However, unlike a commercial company, we are dedicated to developing new treatments for one condition Parkinsons, and doing so as quickly as possible.

A Medical Culture Looking For Symptoms

Parkinsons Disease: Symptoms, Diagnosis and Treatment ...

The essential reason indeed lies in our medical culture of treating a disease. In a study by Meissner WG et al. of 2011 Priorities in Parkinson disease Research published in the scientific journal Nat Rev Drug Discovery, he points out that among dozens of drugs on the market in the care of patients with Parkinsons disease, NONE targets neuroprotection. So no strategy has been developed to stop or slow down the progression of the disease.

Although symptoms can be improved through dopamine replacement strategies, there is an urgent need to reorient current research. The strategy should target treatments producing neuroprotective and/or disease-modifying effects so that patients can hope to see the neurodegenerative process slow down.

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Scientists Are Close To Finding A Cure For Parkinsons Disease

Researchers studied mutant fruit flies to uncover how the disease affects the brain

SCIENTISTS are on the brink of finding a cure for Parkinsons disease after discovering what causes the illness and how it affects brain cells.

Experts previously thought people who fell ill at a younger age than most who develop Parkinsons suffer from a poorly functioning mitochondria.

These are the powerhouses of cells and without reliable sources of energy, neurons wither and die.

But Medical Research Council researchers at University of Leicester found this may not be the complete picture of what is happening within the brain cells affected by Parkinsons.

Now it is thought neuro deterioration occurs in response to stress on the endoplasmic reticulum part of the outer skin of the cell rather than failure of the mitochondria as previously thought.

During the study fruit flies were injected with chemicals to prevent the effects of ER stress and as a result, it prevented the death of neurons which are commonly associated with the disease.

Dr Miguel Martins said: This research challenges the current held belief that Parkinsons disease is a result of malfunctioning mitochondria.

By identifying and preventing ER stress in a model of the disease it was possible for us to prevent neurodegeneration.

Lab experiments, like this, allow us to see what effect ER stress has on Parkinsons disease.

The History Of Parkinsons

Parkinsons disease was first defined as a shaking palsy in 1817 by James Parkinson. Half a century later, in 1872, the Parisian neurologist Jean-Martin Charcot coined the term Parkinsons disease.

Though Parkinson was the first to describe the disease in modern medicine, Charcot and his colleagues revolutionised treatments in the mid-19th century.. Parkinson was a proponent of blood-letting from the neck, in a bid to siphon off inflammatory pathogens and prevent them from reaching the brain. But Charcot and his colleagues favoured pharmaceutical approaches centred around anticholinergic drugs, which block the action of a neurotransmitter called acetylcholine. Anticholinergics are still in use today.

Around the same time, a host of other treatments were being explored at a hospital in Paris. Hyoscyamine, a plant-derived medication, was put in bread and fed to patients. Other medications, such as a derivative of quinine, were mixed with a syrup of orange rinds.

Charcot also claimed to see the symptoms of patients with Parkinsons improving when travelling by train and horse-carriage. He became a proponent of vibration therapy, where patients bodies and heads were shaken vigorously by a rigged motor.

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How Would A Parkinsons Vaccine Work

Parkinsons is associated with the accumulation of Lewy bodies tiny deposits of a protein called alpha-synuclein in the brain. Preventing the build-up of Lewy bodies and removing existing clumps could be an effective way to treat the disease.

Current approaches to Parkinsons vaccines involve the introduction of a molecule that induces the body to produce its own antibodies against a-syn, resulting in active immunity. It is hoped the antibodies will cling to a-syn build-ups and help to break them down.

How Can Stem Cell Technology Help

Why isn’t there a cure for Parkinson’s?

Stem cell technologies show promise for treating Parkinson’s Disease and may play an increasing role in alleviating at least the motor symptoms, if not others, in the decades to come.

“We are in desperate need of a better way of helping people with Parkinson’s disease. It is on the increase worldwide. There is still no cure, and medications only go part way to fully treat incoordination and movement problems,” said Claire Henchcliffe, from Weill Cornell Medical College in the US.

“If successful, using stem cells as a source of transplantable dopamine-producing nerve cells could revolutionize care of the Parkinson’s disease patient in the future,” said Malin Parmar, from Lund University in Sweden.

“A single surgery could potentially provide a transplant that would last throughout a patient’s lifespan, reducing or altogether avoiding the need for dopamine-based medications,” said Parmar.

In the past, most transplantation studies in PD used human cells from aborted embryos. While these transplants could survive and function for many years, there were scientific and ethical issues — foetal cells are in limited supply, and they are highly variable and hard to quality control.

Some patients were treated, while another developed allergy with the graft.

This approach is now rapidly moving into initial testing in clinical trials, researchers said.

The first systematic clinical transplantation trials using pluripotent stem cells as donor tissue were initiated in Japan in 2018.

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Lrrk2 Inhibitor For Parkinsons Disease

Meanwhile, a San Francisco-based biotech company called Denali Therapeutics , which went public back in December 2017, conducted phase 1b of a 28-day clinical trial for its LRRK2 inhibitor, DNL201, late last year. The company says inhibition of LRRK2 activity may potentially slow the progression of Parkinsons disease in patients with a genetic LRRK2 mutation, as well as in patients with sporadic Parkinsons disease. The therapy is designed to correct the lysosomal system, which serves as the landfill and recycling department of the cell. Lysosomal dysfunction is associated with neurodegenerative diseases like Parkinsons.

Some Other General Points

Stay as active as possible. Exercise regularly as much as you are able. This may not be possible when the condition is more advanced. However, it is something to consider when symptoms are not too bad. You may walk more slowly than before but a daily walk is good exercise and may help to loosen up stiff muscles. Well-meaning relatives or friends may tell you to rest and take things easy. However, as much as possible and for as long as possible, resist the temptation for others to do things for you just because it may be quicker.

Constipation is common in people with PD. Help to reduce the chance of this by having lots to drink and eat plenty of vegetables, fruit, and foods high in fibre. Exercise can also improve constipation. Sometimes laxatives may be needed to treat constipation.

Some medicines taken for other conditions can interfere with dopamine and make PD worse. These may be prescribed for such things as mental illness, sickness, vertigo and dizziness. Check with your doctor if you are unsure about any medicines that you take.

Driving. If you are a driver you should tell the DVLA and your insurance company if you develop PD. Your insurance may be invalid if you do not. Depending on the severity of symptoms and the medicines that you are taking, you may still be allowed to drive following a medical assessment.

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