Possible progress against Parkinson's and good news for stem cell therapies

Date:

April 3, 2015

Source:

D'Or Institute for Research and Education

Summary:

Researchers have taken an important step toward using the implantation of stem cell-generated neurons as a treatment for Parkinson's disease. Using an FDA approved substance for treating cancer, they were able to grow dopamine-producing neurons derived from embryonic stem cells that remained healthy and functional for as long as 15 months after implantation into mice, restoring motor function without forming tumors.

Brazilian researchers at D'OR Institute for Research and Education (IDOR) and Federal University of Rio de Janeiro (UFRJ) have taken what they describe as an important step toward using the implantation of stem cell-generated neurons as a treatment for Parkinson's disease. Using an FDA approved substance for treating stomach cancer, Rehen and colleagues were able to grow dopamine-producing neurons derived from embryonic stem cells that remained healthy and functional for as long as 15 months after implantation into mice, restoring motor function without forming tumors.

Parkinson's, which affect as many 10 million people in the world, is caused by a depletion of dopamine-producing neurons in the brain. Current treatments include medications and electrical implants in the brain which causes severe adverse effects over time and fail to prevent disease progression. Several studies have indicated that the transplantation of embryonic stem cells improves motor functions in animal models. However, until now, the procedure has shown to be unsafe, because of the risk of tumors upon transplantation.

To address this issue, the researchers tested for the first time to pre-treat undifferentiated mouse embryonic stem cells with mitomycin C, a drug already prescribed to treat cancer. The substance blocks the DNA replication and prevents the cells to multiply out of control.

The researchers used mice modeled for Parkinson's. The animals were separated in three groups. The first one, the control group, did not receive the stem cell implant. The second one, received the implant of stem cells which were not treated with mitomycin C and the third one received the mitomycin C treated cells.

After the injection of 50,000 untreated stem cells, the animals of the second group showed improvement in motor functions but all of them died between 3 and 7 weeks later. These animals also developed intracerebral tumors. In contrast, animals receiving the treated stem cells showed improvement of Parkinson's symptoms and survived until the end of the observation period of 12 weeks post-transplant with no tumors detected. Four of these mice were monitored for as long as 15 months with no signs of pathology.

Furthermore, the scientists have also shown that treating the stem cells with mitomycin C induced a four-fold increase in the release of dopamine after in vitro differentiation.

"This simple strategy of shortly exposing pluripotent stem cells to an anti-cancer drug turned the transplant safer, by eliminating the risk of tumor formation," says the leader of the study Stevens Rehen, Professor at UFRJ and researcher at IDOR.

The discovery, reported on April in the journal Frontiers in Cellular Neuroscience, could pave the way for researchers and physicians to propose a clinical trial using pluripotent stem cells treated with mitomycin C prior to transplant to treat Parkinson's patients and also other neurodegenerative conditions.

"Our technique with mitomycin C may speed the proposal of clinical trials with pluripotent cells to several human diseases," says Rehen. "It is the first step to make this kind of treatment with stem cells possible."

Story Source:

The above story is based on materials provided by D'Or Institute for Research and Education. Note: Materials may be edited for content and length.

Journal Reference:

1  Mariana Acquarone, Thiago Melo, Fernanda G. Meireles Ferreira, Jordano Brito-Moreira, Gabriel Oliveira, Sergio Ferreira, Newton Castro, Fernanda Tovar-Moll, Jean Christophe Houzel and Stevens K. Rehen. Mitomycin-treated undifferentiated embryonic stem cells as a safe and effective therapeutic strategy in a mouse model of Parkinson's disease. Front. Cell. Neurosci., 2015 DOI: 10.3389/fncel.2015.00097

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D'Or Institute for Research and Education. "Possible progress against Parkinson's and good news for stem cell therapies." ScienceDaily. ScienceDaily, 3 April 2015. <www.sciencedaily.com/releases/2015/04/150403104223.htm>.

http://health.einnews.com/article/258280048/cOSJk4entRAttHsn

Parkinson's diagnosis by typing on a keyboard

by Mariella Moon | @mariella_moon | 9 hrs ago
It's tough identifying Parkinson's disease in its early stages -- there are no standard lab tests to diagnose it and symptoms are subtle. A group of MIT researchers believe the answer could lie in something a lot of people already use: the computer keyboard. They've recently conducted a study proving that people with conditions affecting motor function have different typing patterns than those who don't. To be exact, the researchers designed plug-in software to measure how long subjects pressed each key before releasing it. Those with impaired motor skills ended up pressing keys for a longer duration.

Most of the time, a big part of the brain is already damaged before the illness becomes apparent. An early diagnosis will allow doctors to plan a treatment strategy that slows down its effects. Motor skill impairment, however, doesn't automatically mean Parkinson's. In fact, the study's original goal was to observe the effects of fatigue. After the team determined that it could work as a diagnostic tool for Parkinson's, though, they enlisted the help of 21 patients for more tests.

The team found that those with the condition exhibited "greater variation in the keystrokes" compared to the 15-person control group. Sounds promising, but the results have to be validated in larger studies with people in various stages of the disease, before doctors can start asking possible patients to take typing tests.

[Image credit: Getty Images}

http://health.einnews.com/article/258237416/nd_YZjv_xPXCTrfR

Mitochondria are altered in human cell model of Parkinson's disease

PUBLIC RELEASE: 2-APR-2015

IMAGE: IMAGES ARE OF MITOCHONDRIA FROM IPSC-DERIVED DOPAMINERGIC NEURONS. THE NEURON ON THE LEFT IS FROM A "NORMAL " OR CONTROL IPSC LINE; THE NEURON ON THE RIGHT WAS DERIVED FROM... 

CREDIT: COURTESY OF AKOS GERENCSER, PHD

Based on research in fruit flies, it has long been suspected that the most common mutation linked to both sporadic and familial Parkinson's disease (PD) wreaks its havoc by altering the function of mitochondria in neurons that produce the neurotransmitter dopamine. Using stem cells derived from patients who have PD, scientist at the Buck Institute have confirmed that finding in human cells for the first time. In research published in the April 2nd early online edition of Stem Cell Reports, Buck researchers also provide a valuable tool for testing potential treatments for the progressive, incurable neurodegenerative disease. 

"If we can find existing drugs or develop new ones that prevent damage to the mitochondria we would have a potential treatment for PD," said Buck faculty Xianmin Zeng, PhD, lead scientist on the study. "This is the first time we can show a real and observable change in mitochondria in human cells affected by a PD mutation," she said. 

Mitochondria are energy-producing organelles found in large numbers in most cells and are necessary for life. Zeng says the Park2 mutation altered mitochondrial structure and function in dopamine producing neurons, causing them to die. Dopamine is an essential neurotransmitter which regulates movement and emotion. 

The research involved making mutations in the Park2 gene in well-characterized induced pluripotent stem cell (iPSC) lines as well as generating iPSC lines from skin cells of four patients who have PD. "What we saw was extraordinary," said Zeng. "We saw the same characteristics in the dopaminergic neurons derived from patients as well as ones derived from the lines where the mutation was introduced." 

The finding promises to be significant in the search for treatments for an incurable disease, which affects nearly one million Americans and causes a progressive decline in movement and muscle control. Existing drugs can ease symptoms but often cause troubling side effects over time. While using patient-specific iPSC lines has been held as a potential gold standard for testing potential therapeutics for PD, Zeng says there has always been concern that background genetic differences between patients would render the testing inconclusive for larger populations of PD patients. According to Zeng, this research addresses those concerns and paves the way for testing of compounds for PD in human cells, an activity that is underway in the Buck lab of Julie Andersen, PhD, who also studies PD. 

Zeng, who receives support from the California Institute for Regenerative Medicine (CIRM), says there are up to ten mutations linked to PD. Her lab is developing human iPSC models based on mutations in Pink1, SNCA, Park7 and Lrrk2, which are those more closely implicated in PD. Zeng is also involved in research aimed at getting a stem cell derived treatment for PD ready for testing in humans.

###

Citation: Mitochondrial alterations by Parkin in dopaminergic neurons using Park2 patient-specific and Park2 knock-out isogenic iPSC lines

Other Buck Institute researchers involved in the study include Atossa Shaltouki, Renuka Sivapatham, Ying Pei, Akos Gerencser, and Olga Momcilovic. Mahendra S. Rao, of NxCell Science in Novato, CA, also contributed to the study. The work was supported in part by grants from the California Institute for Regenerative Medicine, TR-01856 and TG2-011155. 

About the Buck Institute for Research on Aging

The Buck Institute is the U.S.'s first independent research organization devoted to Geroscience - focused on the connection between normal aging and chronic disease. Based in Novato, CA, The Buck is dedicated to extending "Healthspan", the healthy years of human life and does so utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and those focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer's and Parkinson's, cancer, cardiovascular disease, macular degeneration, osteoporosis, diabetes and stroke. In their collaborative research, they are supported by the most recent developments in genomics, proteomics, bioinformatics and stem cell technologies. For more information: http://www.thebuck.org

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http://health.einnews.com/article/258108869/pMrUSkgNN66R0mtI

Infographic: Understanding Parkinson's Disease

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APRIL 2, 2015, 9:58 AM    LAST UPDATED: THURSDAY, APRIL 2, 2015                                                                                  

BY R. L. REBACH

STAFF ARTIST | 

NORTHJERSEY.COM

Parkinson's disease is a chronic and progressive movement disorder.

http://health.einnews.com/article/258088958/A2X1xy945OCRRmkM

Malignant Melanoma Risk 4-Fold Higher in Parkinson's

The Connection Between Parkinson's Disease And Melanoma

By Howard Moore,April 2, 2015:00 a.m.

One out of four people will get some form of Cancer in their lifetime. That's bad odds. 25%.One out of five people will get Melanoma in their lifetime. 20% but I don't like those odds any better.If you have Parkinson's it's even worse because there is a connection between PD and Melanoma.It's pretty simple. One of the issues with Parkinson's is vitamin deficiencies. It increases your chances of getting Melanoma. Told you it was pretty simple.

And yet until recently, I didn't know of a single case of a Parkinson's patient having Melanoma.Then it got personal.A few months ago I started researching this topic. I thought it would be interesting to write about. I found a lot of gross photos but not a lot of info. The topic went on the back burner.On Valentine's Day, I noticed this mark on the top of my back. It looked exactly like the picture up above.  I'm pretty sure my first words were "Oh shit, I've got Melanoma". Maybe it was a little stronger.

I was very lucky. Because of the research, I'd seen enough pictures of this to know what was happening. Yeah, I was scared but the knowledge helped.I was also lucky to even see it. It's in a spot where you almost need to be Linda Blair, spinning her head in The Exorcist, to find it.

The next step was to do something about it. I found four people that I knew had dealt with Melanoma and started asking questions. Their answers were pretty much the same.Find out what stage you're in. Ask about further tests. Is chemo needed? What about lymph nodes? How will it get removed? What about follow-ups?

It's a lot to deal with. Your head is spinning but you need to know these things. It helps to have people you can ask about these things. It also helps to have someone go with you to make sure you keep on task and get the answers you need. Thanks to all these folks...very much appreciated!

Like I said earlier, I was very lucky. The Melanoma was microscopic. Less than Stage 1. It's still Cancer and it still needs to come out. That will happen next week.My surgeon says it's a simple surgical procedure. I think a simple procedure is when it happens to someone else. But two hours and I'll be Cancer-free.

So the question is was there a connection between my Parkinson's and the Melanoma? I don't know and the surgeon didn't know either. He did think it was possible. He also thought it was bizarre I was working on a story about this when it happened.

I do, too. Truth is stranger than fiction. Cue the Twilight Zone music.

http://www.chicagonow.com/hippy-shakes/2015/04/the-connection-between-parkinsons-disease-and-melanoma/

PLEASE With the weather getting warmer remember   SUNSCREEN 

Malignant Melanoma Risk 4-Fold Higher in Parkinson's

Megan Brooks.June 25, 2013

SYDNEY, Australia — A new study suggests that patients with Parkinson's disease (PD) have about a 4-fold increased risk for development of malignant melanoma, underscoring the importance of dermatologic screening in PD, the researchers say Radu Constantinescu, MD, from the University of Rochester Medical Center in New York, presented the study here June 18 at the Movement Disorder Society (MDS) 17th International Congress of Parkinson's Disease and Movement Disorders.

Prior studies have shown that the overall risk for cancer in patients with PD is lower but the risk for malignant melanoma is higher compared with the general population. The latter was observed by Dr. Constantinescu and colleagues in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial (Mov Disord. 2007;22:720-722).

In their latest study, they looked at the risk for malignant melanoma in 1741 patients with early, treated PD enrolled in the National Institutes of Health Exploratory Trials in PD Long-term Study-1 (NET-PD-LS-1).

During 6763 person-years of follow-up, there were 13 cases of malignant melanoma in the patients with PD compared with 3.79 cases expected in the general population.

The standard event ratio for malignant melanoma in the NET-PD-LS-1 population was 3.4 (95% confidence interval [CI], 1.8 - 5.9), the researchers say.

"Although more than 20 years have passed and the general awareness in regard to malignant melanoma in PD has increased, the risk observed in the NET-PD-LS-1 study is similar to the one seen in the DATATOP population," the authors say.

This study "documents an approximately 4-fold higher risk of developing melanoma in PD subjects, comparable to what was observed almost 20 years ago in the DATATOP trial," MDS president-elect Matthew Stern, MD, Parkinson's Disease and Movement Disorders Center, University of Pennsylvania, Philadelphia, who wasn't involved in the study, said in a conference statement.

Lisa Cannon-Albright, PhD, from the University of Utah in Salt Lake City, who reviewed the data for Medscape Medical News, said it "does look like yet another confirmation" of the association between melanoma and PD. "I don't see anything new here," she added.

As reported recently by Medscape Medical News, Dr. Cannon-Albright and colleagues uncovered a novel association between PD and prostate cancer and confirmed the association with melanoma in an analysis of the Utah Population Database.

Dr. Stern said the new study "underscores the importance for dermatologic screening in PD patients. Further, elucidating the relationship between PD and melanoma may shed light on the pathogenesis of both disorders," he added.

The authors, Dr. Stern, and Dr. Cannon-Albright have disclosed no relevant financial relationships.

Movement Disorder Society (MDS) 17th International Congress of Parkinson's Disease and Movement Disorders. Abstract 404. Presented June 18, 2013.

Skin Test May Shed New Light on Alzheimer’s and Parkinson’s Disease

April 2, 2015 9:00 

New research has determined that a simple skin biopsy may be able to detect physical indicators of both Parkinson’s and Alzheimer’s disease. Researchers from the University of San Luis Patosi in San Luis, Mexico are presenting their study at the American Academy of Neurology’s 67th Annual Meeting. Using skin biopsies from both healthy individuals and those with various neurological diseases, researchers found that those with Parkinson’s possessed seven times the typical amount of tau proteins while those with Alzheimer’s presented eight times the usual amount of alpha-synuclein protein. “More research is needed to confirm these results, but the findings are exciting because we could potentially begin to use skin biopsies from living patients to study and learn more about these diseases. This also means tissue will be much more readily available for scientists to study,” said the lead researcher of the study. “This procedure could be used to study not only Alzheimer’s and Parkinson’s, but also other neurodegenerative diseases.” To learn more about this study:

Skin Test May Shed New Light on Alzheimer’s and Parkinson’s Diseases

Released: 12-Feb-2015 10:20 AM EST Citations

AAN Annual Meeting, April 2015

Newswise — WASHINGTON, D.C. – 

Scientists have discovered a skin test that may shed new light on Alzheimer’s and Parkinson’s diseases, according to a study released today will be presented at the American Academy of Neurology’s 67th Annual Meeting in Washington, D.C., April 18 to 25, 2015. 

The study showed that skin biopsies can be used to detect elevated levels of abnormal proteins found in the two diseases. 

“Until now, pathological confirmation was not possible without a brain biopsy, so these diseases often go unrecognized until after the disease has progressed,” said study author Ildefonso Rodriguez-Leyva, MD, at Central Hospital at the University of San Luis Potosi in San Luis Potosi, Mexico. “We hypothesized that since skin has the same origin as brain tissue while in the embryo that they might also show the same abnormal proteins. This new test offers a potential biomarker that may allow doctors to identify and diagnose these diseases earlier on.”

For the study, researchers took skin biopsies from 20 people with Alzheimer’s disease, 16 with Parkinson’s disease and 17 with dementia caused by other conditions and compared them to 12 healthy people in the same age group. They tested these skin samples to see if specific types of altered proteins were found—ones that indicate a person has Alzheimer’s or Parkinson’s. 

As compared to healthy patients and ones with dementia caused by other conditions, those with both Alzheimer’s and Parkinson’s had seven times higher levels of the tau protein. People with Parkinson’s also had an eight times higher level of alpha-synuclein protein than the healthy control group.

Alzheimer’s disease is ranked as the sixth leading cause of death in the United States, and 5.4 million Americans are currently diagnosed with Alzheimer’s disease. Parkinson’s disease affects one million Americans, with at least 60,000 new cases reported annually each year.

“More research is needed to confirm these results, but the findings are exciting because we could potentially begin to use skin biopsies from living patients to study and learn more about these diseases. This also means tissue will be much more readily available for scientists to study,” said Rodriguez-Leyva. “This procedure could be used to study not only Alzheimer’s and Parkinson’s, but also other neurodegenerative diseases.”

The study was supported by the National Council of Science and Technology of Mexico. 

Learn more about Alzheimer’s and Parkinson’s diseases at www.aan.com/patients. 

The American Academy of Neurology, an association of more than 28,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson’s disease and epilepsy

http://www.aansneurosurgeon.org/2015/04/02/skin-test-may-shed-new-light-on-alzheimers-and-parkinsons-disease/

Patient's own skin cells may hold key to new treatments for neurological diseases

Published on March 31, 2015 at 1:52 PM 

A patient's very own skin cells may hold the key to new treatments and even cures for devastating neurological diseases. A generous $1 million donation from Mr. J. Sebastian van Berkom, and critical partnerships with Brain Canada, Laval University, Marigold Foundation and the FRQS-Réseau Parkinson Quebec are driving an innovative, iPSC (induced pluripotent stem cell) research platform that will transform research into Parkinson's and other neurological diseases.

Millions of Canadians are affected by diseases of the brain such as ALS, Parkinson's and brain tumours, for which there are limited treatments and no cures. By 2020, neurological conditions will become the leading cause of death and disability. "Everyone's lives are touched in some way by neurological disease, says Mr. van Berkom, President of Van Berkom and Associates Inc." In creating The van Berkom Parkinson's Disease Open-Access Fund, I hope to change lives and support new research that will lead to new treatments and one day cures. The iPSC platform is a new paradigm for neuroscience research and as one of the world's great neuroscience centres, The Neuro is the place to drive it forward."

"This is the ultimate bench to bedside paradigm, from patient to the bench, back to the patient," says Dr. Guy Rouleau, Director of The Neuro. "With a unique interface between fundamental and clinical research, The Neuro is uniquely positioned to be a central hub in the iPSC platform. Partnering with Mr. Van Berkom, a generous and visionary philanthropist, propels The Neuro toward the goal of significantly deepening insight into disease mechanisms with unprecedented efficiency."

Patients' skin cells will be reprogrammed into induced pluripotent stem cells (iPSCs) at Laval University, under the leadership of Dr Jack Puymirat, and then differentiated at The Neuro into disease relevant cells for research. For example, in the case of Parkinson's this could be dopamine neurons. The cells can also be genome-edited, a state-of-the-art technique that can introduce or correct disease associated mutations - creating the most accurate disease models. These iPSCs will be made widely and openly available to researchers across Quebec for neuroscience research. This open-access approach exponentially increases the likelihood of breakthroughs in neurological disease.

"The unique and exciting aspect of this platform is that we are creating the most specific cells for studying disease using the patient's own tissue, which has distinct advantages over using generic cells or animal models," says Dr. Edward Fon, neurologist and co-Director of the Quebec iPSC platform. "Disease models using human samples are increasingly shown to be far more efficacious in trials, as they much more accurately mimic the disease condition. In the iPSC platform, not only can specific mutations be introduced but, cells are from patients' whose specific clinical history and genetic profile are known, a first step on the road toward neurological personalized medicine. The Neuro has access to a large and well-characterized patient population, who can help create a rich clinically-and genetically-derived registry and biobank. The initial targets in the platform will be ALS and Parkinson's disease (PD), using dopamine neurons for PD and both motor neurons and astrocytes for ALS."

Source:

McGill University

http://www.news-medical.net/news/20150331/Patients-own-skin-cells-may-hold-key-to-new-treatments-for-neurological-diseases.aspx