New Treatments For Parkinson’s Disease 2020

How Could Stem Cells Help People With Parkinson’s

Stem cells are the parent cells of all tissues in the body. This means they can turn into any type of cell. The hope is that they will eventually be able to make these cells into specific types of cells, like dopamine-producing neurons, that can be used to treat Parkinson’s disease. However, there are concerns that patients may have the same risk of increased involuntary movements as those who undergo fetal cell transplantation. And, like fetal cell transplantation, stem cell therapy is surrounded by moral and ethical controversy.

Treatments In Phase Ii Trials

Another strategy in the therapeutic research space is drug repurposing. This is when an existing medication for one condition is repurposed to treat an entirely different condition. Working with repurposed medications comes with many advantages including understanding its general safety. Repurposing an existing medication, rather than starting from scratch, typically requires fewer tests for safety as the drug has already met these requirements. This can reduce costs and speed up the process through the clinical trial pipeline. It can also lead to faster approvals, getting much-needed treatments into the hands of people with Parkinsons as soon as possible. There are a total of 74 therapies in Phase II trials and 44% are repurposed medications.

One exciting takeaway from Phase II trials this year is the progress made with stem cell therapies. While there are nine stem cell therapies being explored in Phase I, two stem cell therapies graduated to Phase II trials this year! Moving into Phase II means these treatments are being administered to a larger group of people to monitor their effectiveness and further evaluate their safety.

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Easing Cramps Spasms Or Tremors Due To Parkinson’s

• Massage your legs nightly to relieve leg cramps.
• Take warm baths and use heating pads to help relieve muscle spasms and ease cramps.
• Use mineral ice to relax sore joints and muscles.
• Squeeze a small rubber ball to reduce hand tremors.
• At first indication of a tremor, if possible, try lying on the floor, face down, and relaxing your body for five to 10 minutes.

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How Do Mesenchymal Stem Cells Work In The Body

Mesenchymal stem cells utilize their self-renewal, immunomodulatory, anti-inflammatory, signaling, and differentiation properties to influence positive change within the body. Mesenchymal stem cells also have the capacity to self-renew by dividing and developing into multiple specialized cell types present in a specific tissue or organ. Mesenchymal stem cells are adult stem cells, meaning they present no ethical concerns, MSCs are not sourced from embryonic material.

Other Tips For Those With Parkinson’s Disease

• Purchase a small battery-powered alarm pillbox to help you remember your medication schedule.
• Use a speaker phone or telephone headset to ease the problem of hand tremors while talking on the phone.
• Install an intercom system or purchase walkie-talkies to make contact within the home easier.

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Advances In Deep Brain Stimulation

Deep brain stimulation is another established treatment for PD that is useful in treating dopamine-dependent motor symptoms when levodopa-induced side effects become particularly problematic. DBS involves the surgical implantation of electrodes that stimulate subcortical structures including the subthalamic nucleus and globus pallidus internus9194. DBS offers significant improvements in motor symptoms and fluctuations in comparison to best medical therapy in some advanced PD patients, but dopamine-resistant symptoms other than tremor respond poorly95. It has also been suggested in an open-label trial that DBS is beneficial in early PD patients, with improved tremor scores and reduced development ofde novo tremor96. In addition to surgical complications, DBS strategies may cause cognitive and neuropsychiatric adverse effects as well as speech dysfunction. Novel DBS approaches, including adaptive DBS, targeting different regions, and refined intra-operative imaging techniques promise to offer improved clinical applicability and reduce the impact of adverse effects97.

What Are The Symptoms Of Parkinson’s Disease

Parkinson’s DIsease can include a variety of symptoms that vary in severity and type amongst the affected population. Early signs of the condition can sometimes go unnoticed but as the disease progresses one can expect these symptoms:

• Difficulty speaking
• Difficulty writing
• Loss of automatic movements
• Slowed overall movement
• Muscle stiffness

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Clinical Trial Suggests Parkinsons Drug Is Safe In Humans

A large team of researchers from Denali Therapeutics, working with colleagues from multiple entities in the U.S. and one in Canada, has found that a LRRK2 inhibitor called DNL201 showed no ill effects to volunteers in a clinical trial. In their paper published in Science Translational Medicine, the group describes their clinical trial of the Parkinsons drug and what they learned during its run. Patrick Lewis, with Royal Veterinary College London has published a Focus piece in the same journal issue outlining the work being done by the team at Denali.

Parkinsons disease is a disease that results from the destruction of neurons in the brain that produce dopamine, which is critical for motor function. Prior research has suggested it comes about most often due to environmental factors in people with a genetic risk for it. Prior research has also shown that mutated versions of a certain gene lead to overproduction of an enzyme called LRRK2, which leads to inflammation and other problems. Currently, there are no therapies available to slow its progression.

Science Translational Medicine

by CU Anschutz Medical Campus

Currently, there are no disease modifying therapies for Parkinsons disease that can change the progression of the disease. An international team of scientists led by faculty at the University of Colorado Anschutz Medical Campus is hoping to change that.

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Getting Dressed With Parkinson’s Disease

• Get dressed while sitting in a chair that has armrests — this will help you keep your balance.
• Roll from side to side to get pants over your hips. You can do this while sitting in a chair or lying down on your bed.
• Wear clothes that are loose fitting and have elastic waistbands.
• Choose wrap-around clothing instead of the pullover type. Also choose clothing that opens in the front, not the back so you don’t have to reach behind you.
• Wear clothing with large, flat buttons, zippers, or Velcro closures.
• Use a button hook to button clothing.
• Use a dressing stick if you have shoulder weakness to get your coat or shirt on or off.
• Use a zipper pull or attach a leather loop on the end of the zipper to zip pants or jackets.
• Wear slip-on shoes or buy elastic shoelaces that allow you to slip your shoes on and off without untying the laces. Use devices such as a sock donner and long-handled shoehorn for additional assistance.

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Writing Tips For Parkinson’s Disease

• Use large print, instead of script writing. Try using weighted pens or pencils and wrap black electrical tape around the barrel for additional grip.
• Use felt-tip markers and a large tablet on an easel.
• If you have difficulty using writing utensils, try typing notes or letters on a computer or typewriter.

What Kinds Of Genetic Research Is Being Done

Researchers are investigating genes that code proteins responsible for producing dopamine. By increasing the amount of dopamine in the brain, Parkinson’s symptoms can be minimized if not prevented.

What other treatments are being researched?

• Drug treatments. Researchers are investigating drugs that block the action of glutamate, an amino acid that destroys nerve cells, as well as the role of the antioxidant coenzyme Q-10 in slowing the progression of Parkinson’s disease.
• Neural growth factor. Preliminary studies have shown that neural growth factor revives the dormant cells needed to produce dopamine, dramatically improving symptoms.
• Deep brain stimulation. Research is underway to better understand how deep brain stimulation works in Parkinson’s disease. Researchers are also studying improved ways of stimulating the brain.

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Mesenchymal Stem Cell Therapies For Neurodegenerative Diseases

While there have been significant advances in the symptomatic management of these diseases that improve quality of life and at times survival, the available medications likely only slow the progression of neuronal death by a few months. The idea of using cell therapy to treat neurodegenerative diseases has been around for decades, most notably in Parkinson’s Disease where a variety of cell transplant investigations have been performed with success.

According to a recent study conducted by Nathan P. Staff et al,

“The precise mechanism by which MSCs may exert beneficial effects in neurological disease is still being elucidated, but it appears that multiple different mechanisms may contribute. First, MSCs have been shown to secrete neurotrophic growth factors, including glial cell-derived neurotrophic factor , vascular endothelial growth factor, and brain-derived neurotrophic factor ,which can be further enhanced under specific culture conditions.Neurotrophic growth factors have been shown to improve neuronal survival in a number of preclinical models of neuron injury, including ALS, PD, and MSA transgenic animalsand nerve injury models. â Second, MSCs strongly modulate the immune system and can aid wound healing, and this mechanism has been exploited in disorders such as graft versus host disease and Crohnâs disease. From a neurodegenerative perspective, it has become increasingly recognized that neuroinflammation plays a significant pathomechanistic role.”

What Causes Parkinson’s Disease

Parkinson’s Disease is caused by a loss of nerve cells in the brain. This loss of nerve cells within the brain results in a reduced amount of dopamine being created which acts as a messenger between the parts of your brain that control voluntary and involuntary movement. Therefore without that vital connection, your brain starts losing the ability to effectively control movement. Currently, it is unknown what causes the deterioration of nerve cells associated with Parkinson’s Disease . Currently, it is believed that both environmental factors, as well as genetic factors, may play a role in the loss of nerve cells.

Parkinson’s Disease is a lifelong condition that can greatly impair the ability of one’s daily functions. Traditional treatments only address the symptoms of the condition, but researchers are excited about the possibilities of certain gene therapies and stem cell therapy, which may have the ability to reverse damage and halt the progression of the disease.

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Parkinsons Living Well Stories

• In a recent interview with Parkinsons Life, Davis Phinney shares his story and dedication to living well with Parkinsons and helping countless others do the same. I dont spend much time, if any, musing about things like a cure for Parkinsons, he says. I prefer to focus on the areas that I can positively affect here and now.
• Recognizing that many people with Parkinsons experience handwriting challenges, Neurocrine Biosciences recently launched a Cards to Heroes campaign, designed to encourage people whose handwriting has been affected by Parkinsons to write a brief note of appreciation to their hero. You can learn more about the campaign at pdcardstoheroes.com.
• Two leading Parkinsons experts andJournal of Parkinsons DiseaseEditors-in-Chief have guided the development of a special supplement to theJournal of Parkinsons Disease, which focuses on management strategies to help people living with Parkinsons stay positive and well.

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.

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Studies Show Promising Results

“Considering the ability of MSCs to secrete neurotrophic factors, modulate inflammation, and possibly even act as mitochondria âdonorâ, it comes as no surprise that there is a lot of interest in the use of MSCs in the treatment of Parkinsons Disease, and a multitude of animal studies has shown promise. Treatments have resulted in improvement of motor function, protection of the nigrostriatal system, and improved striatal dopamine release in several studies using toxic lesion rodent models of Parkinsons Disease. Similar effects were reported with umbilical cord-derived MSCs with or without prior differentiation. For example, a recent study reported improvement of motor function, reduced microglial activation, and decreased loss of TH immunoreactivity, associated with local production of trophic factors.

Learn more about DVC Stem’s protocol for Parkinson’s Disease here:

References:

Venkataramana, N. K., Kumar, S. K. V., Balaraju, S., Radhakrishnan, R. C., Bansal, A., Dixit, A., ⦠Totey, S. M. . Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Retrieved from https://www.sciencedirect.com/science/article/pii/S1931524409002205#!

Unified Parkinson’s Disease Rating Scale. . Retrieved from https://www.sciencedirect.com/topics/medicine-and-dentistry/unified-parkinsons-disease-rating-scale

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The Importance Of The Right Endpoints: The Era Of Biomarkers

Mini Assessment

Along with the other key contributors to past failures of disease modification trials in PD, solving the problem of best endpoints is equally critical. Several ideas come into consideration.

Rather than validating candidate progression biomarkers against existing standards, they may need to be validated against disease-relevant and even disease subtype-, stage-, study-, target-, or individual-specific outcomes, as discussed in a recent review .

Deep phenotyping or digital phenotyping would need to sensibly combine a variety of biomarkers and measures.

A scientist and science-driven approach that appropriately regulates industry participation will be required for success . The explosion of consumer electronic technology has led to the burgeoning offerings of consumer fitness and health monitoring products that overlap and encroach the zone of healthcare grade devices, often developed by the same companies as consumer grade monitoring technology. The financial conflicts of interests apply in this area of research and development similarly to other areas, but regulatory response to the rapidly changing field of study simply could not keep up the pace, adding another layer of complexity.

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What Will A Cure For Parkinson’s Look Like

Parkinson’s varies so much from person to person. There are over 40 symptoms of Parkinsons. Tremor. Pain. Hallucinations. Everyones experience is different.

Because of this, there may not be a single ‘cure’.

Instead, we may need a range of different therapies to meet the needs of the individual and their specific form of the condition.

This mix may include treatments, therapies and strategies that can:

• slow or stop the progression of the condition
• replace or repair lost or damaged brain cells
• control and manage particular symptoms
• diagnose Parkinson’s at the earliest possible stage.

And this could involve medical treatments, such as drugs and surgical approaches, as well as lifestyle changes, for example to diet and exercise.

Irlab Celon Target Parkinsons Disease Motor Symptoms

While levodopa can reduce PD symptoms by increasing dopamine levels in the brain, prolonged use can cause increased bouts of dyskinesia during OFF time when the drug has reduced effects. IRLAB Therapeutics and Celon Pharma have Phase II trials aiming to reduce levodopa-induced dyskinesia using two different approaches.

IRLABs mesdopetam, which targets the dopamine D3 receptor, has placebo-controlled Phase II trial results expected the second half of this year. Mesdopetam has estimated peak sales of $226 million in 2026, according to GlobalDatas consensus forecast. GlobalData is the parent company of Clinical Trials Arena.

As a primary endpoint, the Phase II mesdopetam trial assesses change in ON time, defined as hours in the day where patients experience the positive effects of levodopa without the negative effects of dyskinesia. Before and after 12 weeks of treatment, patients record their hours of ON time over the course of 24 hours.

Meanwhile, Celons CPL500036, which targets phosphodiesterase 10A , also has placebo-controlled Phase II results expected this year. The four-week study uses a primary endpoint of the Unified Dyskinesia Rating Scale , which measures the severity of dyskinesia side effects.

Of the two primary endpoints, change in ON time is a better measure than the UDyRS, Kordower says. My understanding is that patients would much rather have less time spent in dyskinesias than decreased magnitude of dyskinesia, he explains.

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Energy Conserving Tips For Those With Parkinson’s Disease

• Simplify your tasks and set realistic goals. Don’t think you have to do things the same way you’ve always done them.
• Plan your activities ahead of time. Space them out throughout the day. Do not schedule too many things to do in one day. Do the things that take more energy when you are feeling your best.
• If needed, rest before and after activities.
• If you become tired during an activity, stop and rest. You may need to finish it on another day or when you feel less tired.
• Do not plan activities right after a meal. Rest 20-30 minutes after each meal.
• Ask for help. Divide the tasks among family and friends.
• Get a good night’s sleep and elevate your head when sleeping. Be careful not to nap too much during the day or you might not be able to sleep at night.
• If your doctor says it’s ok, you may climb steps. You may need to rest part of the way if you become tired. Try to arrange your activities so you do not have to climb up and down stairs many times during the day.
• Avoid extreme physical activity. Do not push, pull, or lift heavy objects that require you to strain.

Parkinsons Articles And Podcasts

• A study published in the journal Brain shows that dopamine systems are affected differently in people with Parkinsons with tremor compared to people without tremor and that this affects cognition as well as motor symptoms. Researchers who explored whether the presence of tremor was associated with levodopas effect on reinforcement learning found that people treated with levodopa who did not have tremor had better reinforced learning skills than did those with tremor, who did better at avoidance learning .
• A recent When Life Gives You Parkinsons podcast episode explores how people with Parkinsons can be their own best advocates.

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