British Crew Rowing the Distance to Improve Understanding of Parkinson’s Disease

JUNE 27, 2018 BY CAROLINA HENRIQUES 

A four-man crew from Britain is hoping to increase understanding of Parkinson’s diseaseby rowing across the Indian Ocean in an attempt to break a world record.

Robin Buttery, Barry Hayes, James Plumley, and skipper Billy Taylor are planning to row for 1,920 hours non-stop, for 65 days straight, all the way from West Australia to Mauritius, with the goal of becoming the fastest four-man crew to row the Indian Ocean.

The effort is an attempt to raise awareness of the disease and raise funds to support research — all while serving as subjects of scientific research aimed at studying the relationship between physical exercise and Parkinson’s.

Buttery, 46, was diagnosed with young-onset Parkinson’s disease two years ago, just before his 44th birthday. He lives in Leicester with his wife, Nicola, and son Rory, and works as a technical instructor at De Montfort University in Leicester.

Determined to show that life does not end with a Parkinson’s diagnosis, he challenged three friends to join him in his attempt to break a world record and serve as an inspiration to the community. The crew members will row non-stop, taking shifts of two hours on, two hours off, for 12 weeks.

They will start their journey in Exmouth, Western Australia, and row 3,600 nautical miles in a 29-foot-long ocean rowing boat until they reach their destination in Port Louis, Mauritius.

Cameras on the boat will film the crew 24/7, gathering footage that will be processed by computers after the journey is complete. Researchers will then analyze the video to study the effects of exercise on Parkinson’s.

Although physicians often prescribe physical exercise for Parkinson’s patients and anecdotal evidence shows that common motor symptoms such as tremors, cramps, and gait issues are improved with exercise, very little is really known about how exactly physical activity affects Parkinson’s patients.

By studying Buttery and his crew mates, professors Helen Dawes, Fabio Cuzzolin, and Johnny Collett of Oxford Brookes University in the U.K. hope to answer questions such as whether endurance exercise is always better than other types of exercise and if endurance exercise affects Parkinson’s patients differently than non-patients.

They will compare the changes in Buttery’s movements with those of his crew mates to investigate how endurance exercise affects the motor skills of Parkinson’s disease patients. They can also enlarge the video to look at any changes in their heart and lung regulation.

By analyzing the progression of Buttery’s motor skills and other Parkinson’s symptoms while exercising, the researchers hope to learn more about how physical activity really affects this disease.

Other researchers will also use this venture as a case study. Oxford Brookes research fellow Shelly Coe, a qualified nutritionist, for example, will monitor how diet impacts the management of Buttery’s symptoms.

All of the information these researchers gather could potentially help with the development of new treatments for Parkinson’s disease.

In addition to serving as subjects of scientific observations and attempting to break a world record, the team is also raising funds for charity. They are hoping to raise a minimum of $350,000 to support the Restoration of Appearance and Function Trust, Clear Trust and the European Parkinson’s Disease Association.

Anyone can support the crew and their goal by buying a mile or by making a donation. Once they depart, a livestream of their journey will be available on their website at:   http://www.rowtheindianocean.com

https://parkinsonsnewstoday.com/2018/06/27/british-crew-plans-row-indian-ocean-increase-parkinsons-understanding/

Combating the Fear of Living with Parkinson's Disease

June 27, 2018   BY "SHERRI WOODBRIDGE"

There is an acrostic I have seen for “fear”:

False

Evidence

Appearing

Real

I am sure the author of that acrostic meant well, and while there is some validity to it, it is not completely accurate. Ask anyone who is dealing with any kind of illness. Speak to an elderly person who knows they only have days, maybe weeks left to live. A mother who is waiting to see if the test results of the baby she carries are accurate. The father who just lost his young wife and must now raise his three young children on his own. Or the single mother who has just lost her job.

These people’s fears don’t just appear real. They are real. Those who live with a chronic illness deal with fear daily. A chronic disease robs you of the joy in your journey, the delight in your day. It steals your contentment and calm, replaces wonder with worry. So what do you do when the worry ogre comes to call? When fear capsizes its ship in your harbor and leaves you to deal with the wreckage? How do you handle the kind of fear that does that?

In his book, “Fearless,” Max Lucado examines fears relating to finances, children, violence, and more. However, he doesn’t address the fears of living with a chronic illness. Yet, tackling the fear of unemployment, our children’s safety, violence, chronic illness, etc., are all dealt with in the same way.

Fear is a feeling or emotion about a perceived threat, either real or imagined. It’s the condition of being afraid. It is having a feeling of dread and hopelessness. It is assuming something terrible is going to come out of a given situation. Having Parkinson’s disease can make you feel like that: afraid, threatened, hopeless.

We fear losing our ability to talk coherently. To sing or dance. To write, read, paint, draw. We fear losing the ability to hold our children or grandchildren, to hug our spouse. We fear having to depend on others for help with everyday tasks. We fear there will be no cure. We fear we will be left to die with this cruel disease instead of the more abstract fear of being hit by an unmanned, runaway ice cream truck.

Fear implies a sense of anxiety and a loss of courage. With fear, there is an intense reluctance to face or meet a specific situation such as Parkinson’s disease. There is an aversion to fear, and rightly so.

One thing I don’t want to be in this battle against Parkinson’s disease is a coward, but it’s certainly easy to let the fears take control and to think about the “what ifs.” This is when I step back and ask myself where my faith lies.

A friend, Ardyce Glessing, shared the following in a Facebook group: “I too have fears of not being able to look after myself and be dependent on my family for everything. I am used to taking care of everyone else and I wish it could stay that way. Somedays I do pretty good and try to carry on and think positive, but at times I just break down and cry from, I guess, a fear of the unknown. Eventually, I get over it and carry on with the rest of my day. I can honestly say it’s always in the back of my mind though. My family is supportive, but I don’t like to continually complain about my problems so just usually say ‘I’m doing good”. Every day I pray for a cure or a medication that stops the progression of PD.”

A recurring theme in facing and combatting fears seems to be having a positive attitude. Although this may seem basic, it’s often hard to muster up courage when you’re facing your little monster every day. I like Ardyce’s fear-buster tip: “Have a good cry.”

There is a legitimate fear in not knowing what the future holds, but thankfully, I believe God holds the future. So, while we can have a good cry now and then, we can also remember God still remains in control, even though all around us it seems life is unraveling.

I think we all have fears, but we seldom talk about those fears. I find myself moving onto other things to distract myself from harmful thoughts that may never amount to anything.

And again, Ardyce is spot on: Sometimes we just need a good cry to wash those fears away.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

https://parkinsonsnewstoday.com/2018/06/27/parkinsons-disease-conquering-managing-fear/

Drug protects neurons in Parkinson's disease

June 27, 2018 by Will Doss, Northwestern University

Systemic treatment of animal models with israpidine, a calcium channel inhibitor, reduced mitochondrial stress that might cause Parkinson's disease, according to a Northwestern Medicine study published in the Journal of Clinical Investigation.

These findings bode well for the STEADY-PD III study, a nationwide clinical trial testing isradipine in patients at Northwestern and over 50 other sites across the United States, according to D. James Surmeier, Ph.D., chair and Nathan Smith Davis Professor of Physiology, and senior author of the study

"Obviously, humans are more complicated than mice, but we're hopeful the trial will be positive," Surmeier said.

Isradipine has recently emerged as a potential treatment for early-stage Parkinson's disease, according to Surmeier. While it was originally intended to treat high blood pressure to reduce the risk of heart attack or stroke, patients who took this drug to treat hypertension also had lower rates of Parkinson's disease—putting it on the map for neurologists and neuroscientists.

Scientists investigating this phenomenon hypothesized that the lower disease rates may have been caused by isradipine's neuroprotective effects on dopaminergic neurons, the death of which is a large contributor to Parkinson's disease symptoms.

Running Hot

Dopaminergic neurons are critical to mobilizing regions of the brain that allow rapid movement in response to events. As a consequence, those neurons are always on "high alert." To ensure that they have the energy necessary to play this sentinel role, dopaminergic neurons keep their mitochondrial power-plants running at nearly full capacity, Surmeier said.

"They tune up cellular respiration so that no matter what kind of demand or unexpected excitation comes their way, they can continue to do their job," Surmeier said.

While it's useful in fight-or-flight situations, running "hot" for so long can produce toxic compounds that eventually kill the neurons, as seen in Parkinson's disease.

"Humans, in general, are not confronted with this kind of demand anymore," Surmeier said. "In our distant past, we had unexpected dangers all around and we had to be ready to escape or attack if we were to survive—that's not the situation anymore, particularly if you're 50 years old."

In experiments, isradipine inhibits calcium channels that stimulate mitochondria. By inhibiting these channels, mitochondrial respiration slows and their production of damaging compounds drops.

However, it was unclear if giving israpidine to live mice through the circulatory system would achieve the same effect—particularly when administered over a long period of time and at doses that are tolerated by humans.

From Mice to Men

In the current study, the scientists treated adult mice with isradipine for over a week and then measured the calcium levels in dopaminergic neurons using two-photon laser scanning microscopy—one of the first studies to use quantitative imaging to measure calcium levels inside cells, according to Surmeier.

They found that calcium levels in dopaminergic neurons were lowered after treatment, demonstrating the calcium channels were being inhibited in live models. In addition, this showed a drug didn't lead to an up-regulation of calcium channels that would undermine the goal of treatment, Surmeier explained.

"Often when you perturb cells, they'll compensate—if you knock out a protein, another protein with a similar function is up-regulated to compensate," Surmeier said. "When the the gene for the channel that controls mitochondria was knocked out early in development of dopaminergic neurons, the neurons up-regulated the expression of another channel that filled in for the lost channel."

In addition, the study found the mitochondria of dopaminergic neurons treated with isradipine had lower oxidant stress than in untreated neurons.

Using a genetically encoded probe to measure mitochondrial turnover, they found that the high oxidant stress in dopaminergic neurons caused mitochondrial damage, forcing the neurons to replace these key organelles more frequently than in other healthy neurons. However, by lowering mitochondrial stress, isradipine diminished the damage to mitochondria and reduced turnover.

"We diminished the damage being done to mitochondria enough that dopaminergic neurons looked the same as neurons that are not lost in Parkinson's disease," Surmeier said.

Further, there were no serious side-effects and the animals' behavior was normal, indicating the therapy may work in human patients. However, that question won't be answered until the results of the STEADY-PD III trial are available in the spring of 2019.

Tanya Simuni, MD, chief of Movement Disorders in the Ken & Ruth Davee Department of Neurology and Arthur C. Nielsen, Jr., Research Professor of Parkinson's Disease and Movement Disorders, is the primary investigator of the multicenter study funded by the National Institute of Neurological Disorders and Stroke.

"These data provide additional strong pre-clinical rational for the ongoing phase III study of israpidine in human patients," Simuni said. "We are cautious as so many drugs have failed, but if successful, isradipine will be the first drug to demonstrate the ability to slow progression of Parkinson's disease."

However, it's unlikely any single Parkinson's disease therapy will be a magic bullet—instead, Surmeier views isradipine as part of a multi-faceted therapy, with components targeting different elements of the disease mechanism.

"If you can partially inhibit a few different links in the disease chain, the net effect is very large, but the side-effect profile is manageable," Surmeier said. "We're hopeful isradipine works, but it's likely an optimal therapy will be one that targets a few elements."

More information: Jaime N. Guzman et al. Systemic isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress, Journal of Clinical Investigation (2018). DOI: 10.1172/JCI95898

https://medicalxpress.com/news/2018-06-drug-neurons-parkinson-disease.html

FoxFeed Blog: Ask the MD: What Is Focused Ultrasound?

Posted by Rachel Dolhun,MD,   June 26, 2018

When it comes to treating Parkinson's movement symptoms, patients and doctors have a variety of options, including exercise regimens, medications and surgical therapies such as deep brain stimulation (DBS). And researchers are working to improve and expand treatments to cover more symptoms in broader populations of people with Parkinson's. In recent years, focused ultrasound has entered clinical trials for Parkinson's.

What Is Focused Ultrasound? 

Focused ultrasound is a non-invasive procedure that uses ultrasound waves to destroy brain cells that cause movement problems. (It's sort of like using a magnifying glass to focus sunlight rays on a leaf to make a tiny hole.) The targeted brain cells are part of the basal ganglia, the circuit that controls normal movement and is affected in Parkinson's.

What Can It Treat?

Clinical trials are testing focused ultrasound for Parkinson's tremor that doesn't respond to medication and for dyskinesia: uncontrolled, involuntary movements that can develop with long-term use of levodopa and many years of Parkinson's. Depending on what they're treating (tremor or dyskinesia), researchers direct the ultrasound waves at a different set of cells within the basal ganglia. MRI brain imaging guides ultrasound beams to the right location.

The therapy is U.S. Food and Drug Administration (FDA)-approved to treat essential tremor, a movement disorder that typically causes shaking of the hands with activity.

What Are the Possible Pros and Cons? 

Focused ultrasound does not require surgical incisions or general anesthesia. It's typically a one-time procedure that produces immediate symptomatic benefit. Like all currently available therapies, it is not a cure.

Right now, the procedure is usually only performed on one side of the brain (can be either the right or the left) because of possible speech, swallowing and cognitive problems when done on both sides. This means it eases symptoms only on one side of the body. Also, infection and bleeding can occur, but these are somewhat uncommon side effects.

How Does It Differ from Deep Brain Stimulation? 

The two procedures target the same brain areas. Unlike deep brain stimulation, focused ultrasound does not require placement of wires in the brain, batteries that need recharging or replacement, or devices that entail doctor appointments for programming. However, focused ultrasound also is irreversible because it involves destruction of cells.

What Trials Are Ongoing? 

Current studies are evaluating whether focused ultrasound could ease dyskinesia and motor fluctuations: alterations between "on" time, when symptoms are controlled, and "off" time, when symptoms return. Read more about a recruiting study at: https://foxtrialfinder.michaeljfox.org/trial/5101/

Researchers also are looking at focused ultrasound for Parkinson's tremor, and early indications suggest the therapy may be safe and beneficial.

Who Might Benefit from This Therapy? 

If approved for Parkinson's, focused ultrasound may be an option to treat symptoms in those who can't or don't want to undergo deep brain stimulation. Some people are unable to undergo surgical procedures because of heart or bleeding problems. Others aren't DBS candidates because of cognitive problems. Still others don't want to manage the logistics of DBS programming and future battery replacements. Focused ultrasound could expand the choices of available treatments for patients and doctors.

https://www.michaeljfox.org/foundation/news-detail.php?ask-the-md-what-is-focused-ultrasound

The ABCs of Parkinson’s Disease: The Letter B, Balance and Botox

June 25, 2018  BY "SHERRI WOODBRIDGE"

The letter B is for balance and Botox.

Balance

Many people with Parkinson’s experience walking or balance problems, which can occur in differing degrees. Gait problems can range from the disease slowing your speed, to a lessening of your arm swing and steps that tend to mimic shuffling instead of having a regular stride. You may also struggle with difficulty getting started or freezing in place. Experiencing problems with your balance can cause unsteadiness and falls that make everyday tasks challenging and frustrating.

These symptoms can be tough to treat, but there are ways to manage them: medication adjustment, exercise, and physical therapy. A home safety evaluation may also help.

There are exercises to improve balance for people with Parkinson’s disease. Plus, you can learn methods for getting back up after a fall to avoid injury as much as possible.

Botox

And what else is connected to Parkinson’s disease that begins with “B”?

Why, Botox, of course. People have Botox injections for many different reasons, but in Parkinson’s disease, researchers have found it to be a great help for those suffering from dystonia.

Dystonia is the contraction of a muscle or group of muscles. These contractions can often cause painful and abnormal positions of various parts of the body, for example, the curling of a patient’s toes.

Botox is injected into the affected muscles. The contracted muscles are weakened by the use of Botox, causing them to return to a more normal state. Because of its short effectiveness duration, Botox will most likely need to be reinjected every three to four months.

My neurologist talked about the benefits of Botox for relieving the areas where I was suffering from dystonia, mainly in my back and neck. He injected me with Botox, and within two days I could move my neck again and the pain in my back subsided. It made a world of difference.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

https://parkinsonsnewstoday.com/2018/06/25/abcs-parkinsons-disease-letter-b-balance-botox/

Safer Way of Stimulating Neural Stem Cells for Therapies and Research Developed

JUNE 26, 2018  BY ALICE MELÃO I

A new device that can increase the production of viable neural stem cells may change the landscape of neural stem cell therapies as potential strategies for neurodegenerative and chronic diseases, including Parkinson’s and Alzheimer’s.

The invention, developed by a team at Hong Kong Baptist University (HKBU), was recently awarded with the Gold Medal with Congratulations of Jury at the 46th International Exhibition of Inventions of Geneva, held in April.

Stem cell therapy uses stem cells — a type of cell that can give rise to almost any other cell in the body — to cultivate new and normal cells, or tissues or organs that are then transplanted back into patients to restore physiological functions lost to damaged or dead cells.

Traditional methods of proliferating and differentiating neural stem cells, however, require a large number of certain molecules, known as growth factors. These factors can also stimulate the growth of cancer cells and increase a person’s risk of developing tumors post-transplant.

The newly developed device uses a technology known as inorganic sculptured extracellular nano matrices (iSECnMS): a tiny Z-shaped layer made of biocompatible materials that aims to not trigger adverse reactions from the cells.

The system is designed to avoid the need for growth factors or other components during cell manipulation, and still be able to simulate stem cells’ natural environment for growth.

After growth and cell differentiation, mature cells can become therapeutic agents for stem cell therapy.

“The neural stem cells are under ‘physical massage’ when they come into physiological contact with the matrix we developed,” Jeffery Huang Zhi Feng, PhD, associate professor at HKBU and one of the inventors, said in a university news release. “The ‘physical massage’ resembles the Chinese medicine acupuncture technique which causes the cells to differentiate into functional cells that are in urgent demand in cell replacement therapy.”

Ken Yung Kin-lam, who also helped in developing the device, said this system may provide a safer platform for research into stem cell therapies, as well as help boost the regenerative medicine field.

Based on their proprietary invention, the researchers have established the company Mat-A-Cell Limited  to enable other research institutions and companies to access to this technology for research.

The team has also filed a patent application with the United States Patent and Trademark Office.

https://parkinsonsnewstoday.com/2018/06/26/device-offers-safer-way-of-stimulating-neural-stem-cells-for-therapy-research/

Deep Brain Stimulation May Increase Levels of Inflammatory Factors in Parkinson’s, Study Suggests

JUNE 26, 2018 BY MARTA FIGUEIREDO IN NEWS.

Deep brain stimulation (DBS) may increase the levels of hepcidin — a hormone associated with iron accumulation and inflammation in the brain — in Parkinson’s disease patients, according to a small Polish study.

The study, “Higher serum levels of pro-hepcidin in patients with Parkinson’s disease treated with deep brain stimulation,” was published in the journal Neuroscience Letters.

As people age, iron accumulates in several brain regions and cells, including the microglia (the immune cells of the brain) and the astrocytes (cells that regulate nerve cell communication and survival ).

Increased iron accumulation, as well as brain inflammation, is associated with oxidative stress and cellular damage and is observed in several neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease.

Hepcidin, an iron balance-regulatory hormone, suppresses ferroportin (FPN1) — the protein that transports iron out of cells — and leads to cellular iron accumulation.

Because inflammation can induce the production of hepcidin, this hormone may be a link between brain inflammation and iron-induced oxidative damage, both of which are involved in neurodegeneration in Parkinson’s patients.

Researchers in Poland evaluated the levels of pro-hepcidin — the precursor of hepcidin — in Parkinson’s patients treated only with medication, in those who, in addition to medication, also received DBS, and in healthy people (controls).

DBS — high-frequency stimulation in strategic brain areas through surgically implanted thin wires in the brain — is a treatment strategy for people with advanced Parkinson’s disease whose motor problems do not improve with medication.

Several studies have shown that DBS reduces motor symptoms as well as the necessary daily dose of medication, and improves patients’ quality of life.

Blood samples were collected from 52 people with Parkinson’s disease (25 women and 27 men) with a mean age of 56, and 31 healthy individuals (15 women and 16 men) with no history of neurodegenerative disorders in the family and a mean age of 58.

Among Parkinson’s patients, 37 had been treated only with medication — levodopa (L-DOPA) and/or ropinirole (Requip) — and 15 with additional DBS (with a mean time from implantation of 28.4 months).

Parkinson’s patients had significantly higher levels of pro-hepcidin compared to healthy individuals, supporting the involvement of hepcidin in Parkinson’s disease.

Those treated with medication and deep brain stimulation showed the highest levels of pro-hepcidin. There was no association between hepcidin levels and the duration of DBS, patient’s age, duration of the disease, or medication dose.

Since DBS has been associated with the activation of microglia and astrocytes — which release inflammatory molecules — researchers hypothesized that the overproduction of pro-hepcidin in these patients may be related to DBS and its associated inflammation.

But considering the small group of patients treated with DBS, additional studies are needed to clarify this association and whether it affects the worsening of Parkinson’s disease.

“The results obtained should be interpreted very carefully but are an interesting observation that requires further research, including a larger group of patients,” the researchers wrote.

https://parkinsonsnewstoday.com/2018/06/26/deep-brain-stimulation-dbs-parkinsons-increase-inflammatory-factor-levels/

FDA Grants Regenerative Medicine Advanced Therapy Designation to VY-AADC for Parkinson’s

JUNE 25, 2018 BY JOSE MARQUES LOPES, PHD

The U.S. Food and Drug Administration granted Voyager Therapeutics’ gene therapy candidate VY-AADC regenerative medicine advanced therapy (RMAT) designation for the treatment of therapy-resistant motor fluctuations in Parkinson’s patients.

The RMAT designation, recently created by the FDA, is given to regenerative medicine products intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition, and that have early clinical evidence supporting their effectiveness.

This designation enables early interactions with the FDA to discuss intermediate evidence to support accelerated approval and meet post-approval requirements.

“The RMAT designation was based on our Phase 1b clinical data with VY-AADC and represents an important milestone for the program and recognition of this gene therapy as a potential treatment for Parkinson’s,” Robert Pietrusko, senior vice president of regulatory affairs and quality assurance at Voyager, said in a press release.

Parkinson’s is characterized by the loss of dopamine-producing neurons in the substantia nigra, a brain region key in controlling movement. Neurons in the substantia nigra release dopamine into an area of the brain called putamen, which contains dopamine receptors.

Although effective in the early stages of Parkinson’s, the effectiveness of levodopa — a standard Parkinson’s treatment — gradually decreases with disease progression. As a result, patients experience longer periods of reduced mobility and stiffness, where medication is not effective — called off periods — and shorter episodes where motor symptoms are controlled with medication, or on periods. This is referred to as motor fluctuations.

An enzyme called 1-amino acid decarboxylase (AADC) regulates the generation of dopamine from levodopa. Because AADC levels are reduced in the putamen of Parkinson’s patients, the conversion of oral levodopa to dopamine is limited.

VY-AADC, which consists of a modified, harmless adeno-associated virus, is intended to deliver the DDC gene — which contains the instructions for making AADC — directly into the putamen.

According to Voyager, VY-AADC has the potential to increase the generation of dopamine in a durable manner, and provide clinically meaningful improvements by restoring motor function and improving symptoms.

Voyager’s ongoing Phase 1b clinical trial in Parkinson’s patients showed that a one-time administration of VY-AADC led to robust and sustained improvements in motor function, as well as marked reductions in the use of levodopa and other medications.

The investigational treatment was well-tolerated, and has not caused any serious adverse events to date.

Besides Parkinson’s, Voyager is collaborating with pharmaceutical companies and academic institutions to develop its gene therapy approach for patients with amyotrophic lateral sclerosis (ALS) due to mutations in the SOD1 gene, Huntington’s, Friedreich’s ataxia, Alzheimer’s, and severe, chronic pain.

The U.S. Food and Drug Administration granted Voyager Therapeutics’ gene therapy candidate VY-AADC regenerative medicine advanced therapy (RMAT) designation for the treatment of therapy-resistant motor fluctuations in Parkinson’s patients.

The RMAT designation, recently created by the FDA, is given to regenerative medicine products intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition, and that have early clinical evidence supporting their effectiveness.

This designation enables early interactions with the FDA to discuss intermediate evidence to support accelerated approval and meet post-approval requirements.

“The RMAT designation was based on our Phase 1b clinical data with VY-AADC and represents an important milestone for the program and recognition of this gene therapy as a potential treatment for Parkinson’s,” Robert Pietrusko, senior vice president of regulatory affairs and quality assurance at Voyager, said in a press release.

Parkinson’s is characterized by the loss of dopamine-producing neurons in the substantia nigra, a brain region key in controlling movement. Neurons in the substantia nigra release dopamine into an area of the brain called putamen, which contains dopamine receptors.

Although effective in the early stages of Parkinson’s, the effectiveness of levodopa — a standard Parkinson’s treatment — gradually decreases with disease progression. As a result, patients experience longer periods of reduced mobility and stiffness, where medication is not effective — called off periods — and shorter episodes where motor symptoms are controlled with medication, or on periods. This is referred to as motor fluctuations.

An enzyme called 1-amino acid decarboxylase (AADC) regulates the generation of dopamine from levodopa. Because AADC levels are reduced in the putamen of Parkinson’s patients, the conversion of oral levodopa to dopamine is limited.

VY-AADC, which consists of a modified, harmless adeno-associated virus, is intended to deliver the DDC gene — which contains the instructions for making AADC — directly into the putamen.

According to Voyager, VY-AADC has the potential to increase the generation of dopamine in a durable manner, and provide clinically meaningful improvements by restoring motor function and improving symptoms.

Voyager’s ongoing Phase 1b clinical trial in Parkinson’s patients showed that a one-time administration of VY-AADC led to robust and sustained improvements in motor function, as well as marked reductions in the use of levodopa and other medications.

The investigational treatment was well-tolerated, and has not caused any serious adverse events to date.

The U.S. Food and Drug Administration granted Voyager Therapeutics’ gene therapy candidate VY-AADC regenerative medicine advanced therapy (RMAT) designation for the treatment of therapy-resistant motor fluctuations in Parkinson’s patients.

The RMAT designation, recently created by the FDA, is given to regenerative medicine products intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition, and that have early clinical evidence supporting their effectiveness.

This designation enables early interactions with the FDA to discuss intermediate evidence to support accelerated approval and meet post-approval requirements.

“The RMAT designation was based on our Phase 1b clinical data with VY-AADC and represents an important milestone for the program and recognition of this gene therapy as a potential treatment for Parkinson’s,” Robert Pietrusko, senior vice president of regulatory affairs and quality assurance at Voyager, said in a press release.

Parkinson’s is characterized by the loss of dopamine-producing neurons in the substantia nigra, a brain region key in controlling movement. Neurons in the substantia nigra release dopamine into an area of the brain called putamen, which contains dopamine receptors.

Although effective in the early stages of Parkinson’s, the effectiveness of levodopa — a standard Parkinson’s treatment — gradually decreases with disease progression. As a result, patients experience longer periods of reduced mobility and stiffness, where medication is not effective — called off periods — and shorter episodes where motor symptoms are controlled with medication, or on periods. This is referred to as motor fluctuations.

An enzyme called 1-amino acid decarboxylase (AADC) regulates the generation of dopamine from levodopa. Because AADC levels are reduced in the putamen of Parkinson’s patients, the conversion of oral levodopa to dopamine is limited.

VY-AADC, which consists of a modified, harmless adeno-associated virus, is intended to deliver the DDC gene — which contains the instructions for making AADC — directly into the putamen.

According to Voyager, VY-AADC has the potential to increase the generation of dopamine in a durable manner, and provide clinically meaningful improvements by restoring motor function and improving symptoms.

Voyager’s ongoing Phase 1b clinical trial in Parkinson’s patients showed that a one-time administration of VY-AADC led to robust and sustained improvements in motor function, as well as marked reductions in the use of levodopa and other medications.

The investigational treatment was well-tolerated, and has not caused any serious adverse events to date.

https://parkinsonsnewstoday.com/2018/06/25/vy-aadc-granted-fda-rmac-designation/