A Test to Determine Rate of Dopamine Loss in PARKINSON’S DISEASE

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Loss of dopamine in neurons is a given in the cause of PARKINSON’S DISEASE, but there has been no non-invasive way to measure how much dopamine has been lost or what the rate of dopamine loss might be.  Clinical treatment and dopamine replacement therapies could be made more exact if this could be determined.

A team of investigators from the Cognitive Aging Laboratory at Georgetown University have devised a test that may help neurologists determine the amounts of dopamine lost  on an individual basis for people with PARKINSON’S DISEASE.  It is an amazingly simple test, but the early small study has shown good results.

The Triplet-Learning Task (TLT) was developed by Katherine R. Gamble, who is a psychology student working on a Ph.D. Her senior investigator is Darlene Howard, Ph.D. .  It is based on implicit learning, a type of learning that occurs without awareness.  The brain region that is involved in implicit learning is the caudate nucleus, which is also affected by the loss of dopamine in PARKINSON’S DISEASE..

The test does not involve any complex motor skills: it is a sequential learning task.  Subjects are shown four open circles and two red dots.  They are asked to respond when a green dot appears.  After a bit of practice, subjects quickly learn how to determine where that green dot will appear and their response time become fasters and their responses more accurate.  However, with a loss of dopamine, response time becomes slower and accuracy falters.    This may prove to be a valuable, non-invasive test to help neurologists determine what stage of the disease process the patient is experiencing  or to measure if the amount of dopamine replacement is adequate or effective.

 

 

Georgetown University Medical Center (2013, November 9). Simple dot test may help gauge progression of dopamine loss in Parkinson’s disease. ScienceDaily. Retrieved November 12, 2013, from http://www.sciencedaily.com­/releases/2013/11/131109192838.htm

 

Review by Marcia McCall

 

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Laser Therapy a New Hope for PARKINSON’S DISEASE

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Aggregates of alpha-synuclein in brain cells of people with PARKINSON’S DISEASE have long been the target of research hoping to cure or at least alleviate the symptoms of dementias often associated with PARKINSON’S DISEASE.  Newly publicized research from Chalmers University of Technology in Sweden together with Wroclaw University of Technology in Warsaw, Poland found that it is possible to use a laser driven technology to distinguish the formations of alpha-synuclein proteins from the formations of other functionally beneficial and necessary proteins in the brain.  The same technique, called “multi-photon laser technique” could also be used to eliminate those aggregated proteins..

These researchers believe that the ability to target these misfolded proteins that are believed to be part of the disease process for many dementia type diseases, including Alzheimer’s, PARKINSON’S,  and Lewy Body diseases may enable them to be destroyed by laser instead of by taking multiple drugs to counter their activity.  Photo acoustic therapies, such as these researchers discuss, has already been used to destroy cancer tumors in certain specific settings.  During this therapy, the specific light wave energy of the laser is converted to heat on targeted specific light wave sensitive receptors on the cells.  The heat generated then destroys that targeted cell.

This treatment for destroying alpha-synuclein misfolded proteins is a very new, “on the cutting edge of research” technology.  As with all new procedures and technologies, a lot of studies will need to be done before it can be made widely available to treat people with PARKINSON’S DISEASE.  It would be a non-surgically invasive procedure and would potentially reduce the use of medications while wiping out the dementia caused by accumulations of alpha-synuclein.

With Thanks to

Piotr Hanczyc, Marek Samoc, Bengt Norden. Multiphoton absorption in amyloid protein fibresNature Photonics, 2013; DOI: 10.1038/nphoton.2013.282

 

Reviewed by Marcia McCall

 

Picture Credit’s

http://www.presstv.ir/detail/2013/11/05/333191/study-lasers-may-cure-brain-diseases/

Modern Versus Ancient Treatment for PARKINSON’S DISEASE

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PARKINSON’S DISEASE is a serious and complex neurodegenerative disease that has wide ranging effects.  The tremors, stiffness and rigidity and the slowness that PARKINSON’S DISEASE brings to the body of the affected person extends to the intellectual, emotional and social domains, too.  Every aspect of the person’s life feels the impact of this disease, and then that impact affects the people with whom that person associates.

Western modern medicine excels in attempting to treat the physiological symptoms, but is not so excellent at treating the well being of the affected person.  And therein lies a major challenge for the treatment of PARKINSON’S DISEASE.  Western medicine prides itself for being scientific and objective.  It sees diseases as discreet entities with specific causes that if eliminated or repaired will restore the body to health and thus the patient will be cured.  Diagnosis is about naming the cause and thereby providing a target at which treatment is directed and the patient becomes simply the location where that target resides.  This paradigm grants incredible authority and power to the physician and diminishes the involvement of the patient.  The elevation of technology in Western culture, with its own technological language, spoken only by “specialists” wearing white coats working with specialized high-tech medical machines really renders the patient helpless to understand what is going on and limits their ability to be involved in their own physical processes.

Modern medicine seems like a powerful miracle enacted upon the body of the patient…disease is primarily a bodily dysfunction, and it must be fought and conquered.  Even the language used to describe this is language of war…the disease causing entities (cells, virus, bacteria) are seen as “invaders” that “trigger” “waves” of reactions and  ”attack” the body’s ability to “combat” the disease”.  Research is looking for the “magic bullet”, the nation fights the “war on drugs”, people affected with a virus are “innocent victims”.

Focus of Western medicine is based on biology and chemistry…the “hard” sciences.  It is a simplification that splits the body from the mind, the disease from the patient and allows for more focus on “data”.  If “symptoms” do not show a cause in laboratory tests, imaging studies or with other “diagnostic” tools,  and if all tests are normal, then “nothing” must be wrong, or if something unusual does show up, then it is “abnormal”.  In fact, here in the United States, we have become obsessed with tracking our bodies’ functions…the use of individual blood pressure monitors, blood sugar monitors, pedometers, even “apps” on phones to remind us to record what we ate, when, or even to tell us when to do what!  We have become skilled at examining the “abnormal” symptoms of normal.

This simplification that splits body from mind has some serious consequences.  If the tests are “normal” and “nothing is wrong”, then the patient must be “imagining things”.  If it cannot be objectified or quantified it must not be “real”, or it exists only in the mind.   Only the body gets to have “real” illnesses, everything else then seems less real and possibly reflects a “character defect” or some lapse of self discipline in managing one’s emotions. This dual vision, this body/mind split is an illusion.  The body and the mind are not an either/or proposition.  This illusion is what is not real.

Today, many Western physicians recognize the oversimplification of the body/mind split, but find it very difficult to integrate into clinical practices that demand limited face to face time with a patient and expect detailed dictations.  Cultural differences have been acknowledged and the fact that cultural contexts can define how a patient understands disease.  But it is not just the culture of the patient that affects the treatment, it may also be the culture of the physician who is dispensing it.  The physician may be well trained in Western scientific medicine, but that physician also comes from a world or cultural experience that influences his/her world view and relationship to the patient.

Another area that separates the patient from their disease is the new trend and requirements for digitized records and making a person’s health information available to multiple points in diagnostic and treatment facilities.  Having a patient’s complete medical record at hand may assure more comprehensive treatment for the patient while simplifying the treatment process for the professionals involved.  But the patient as a person can feel somewhat abandoned and secondary to the professional’s attention to the computer and the need to enter every detail into the record.

PARKINSON’S DISEASE has been around for thousands of years.  It has been described in the literatures of nearly every civilization.  While today there exist many modern medicines that help treat the symptoms of this disease, there is still no known cure.  In those years before the advent of modern medicine, people found many ways to treat  and deal with this disease. They were no more able to cure the disease than modern medicine is today, yet people sought and responded to the treatments prescribed, which may or may not have been as effective as today’s treatments.  What benefit they offered perhaps came from treating the patient as a whole person, not limiting treatment to only the symptoms of the disease.

The allure of culturally alternative medicine is often that it gives the patient a measure of control over their treatment process.  It values the mind as much as the body and tries to integrate them in a more balanced approach.  Traditional Chinese or Ayurvedic medicines take into consideration a patient’s whole situation, their personal relationship, social standing, occupational, financial, familial situations.  Other cultures value the association of emotional states or experiences with physical symptoms. Symptoms are not simply data, but part of the person’s lived experience and how those symptoms are expressed and experienced are as much a part of the healing process as are the drugs and therapies used to treat them.  And, indeed, what is today modern medicine grew out the roots these sometimes ancient, but basic  practices of human wellness techniques.

 

Marcia McCall

 

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New Drugs for Parkinson’s Disease Under Development

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Lundbeck Pharmaceuticals is working on developing two new drugs to treat PARKINSON’S DISEASE from two different perspectives and they have received a large grant to help fund this promising research.

The first approach is directed at eliminating or at least preventing alpha synuclein from entering the nervous system.  Presently, Lundbeck has developed a line of anti-bodies that bind with alpha-synuclein and one those anti-bodies has shown a direct effect in animal models of PARKINSON’S DISEASE.  Their hope is to develop the best antibody with the potential to slow the progression of PARKINSON’S DISEASE in people or to perhaps, eliminate it altogether.  A human medical model is still a ways off, and lots of work remains to be done, but this company is definitely up to the task.

Their next project involves creating a symptomatic treatment that does not involve the dopamine receptors in the brain.  They are focused on a so-called “orphan G-protein” in a part of the brain that controls the motor system.  Already they have several drugs that can control the activity of this protein.  Their hope for this project is to create a new type of drug for treatment of the motor symptoms of PARKINSON’S DISEASE that does not have the side effects of current medications.  We all hope that success comes SOON!

Learn more about Lundbeck Research and Development

Review by Marcia McCall

Implant to Help Slow PARKINSON’S DISEASE

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Dr. Steven Gill has been researching the benefits of Glial-cell line Derived Neurotrophic Factor (GDNF)  in PARKINSON’S DISEASE for many years.

Together with his team of researchers from Frenchay Hospital in Bristol, United Kingdom, he had developed a new implant device to deliver GDNF directly to the affected area of the brain.

GDNF has been shown to be an especially potent factor for dopaminergic cell survival and for improving motor deficits such as those seen in PARKINSON’S DISEASE.

Finding ways to deliver GDNF to the affected areas in appropriate ways has been the challenge

The new device developed by this team consists of a small port surgically implanted behind the patient’s ear.

From this port, a system of tubes connects to the basal ganglia and regulated dose of GDNF can be pumped directly to the brain once a month.

To date, six patients have undergone this treatment and the team is now recruiting 36 more patients for a new trial.

If this treatment technology proves successful and safe, many other neurological diseases will be able to benefit from this technique.

Review by Marcia McCall

 

 

 

review by Marcia McCall

Highlights From the World Parkinson Congress 2013

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Memory and Mood Program Presented at the 2013 Parkinson’s World Conference

Sarah K. Lageman, Ph.D., from the Virginia Commonwealth University, Richmond, VA Speaking at the Montreal 2013 World Parkinson’s Conference, presented an abstract of a program she developed with her colleagues that helps people with PARKINSON’S DISEASE enhance their memory and improve their problem solving skills.  Cognitive impairment is one of the biggest obstacles to independent living faced by people with PARKINSON’S DISEASE.  In this small study, participants met once a week and learned practical techniques to help their memory, such as writing in a memory book and using a calendar along with problem solving steps. They also were part of a support group that was client centered where they could share their frustrations and techniques.  Although the numbers in this study are small, the improvements have been large.  “If a neurocognitive program can help keep people functioning better at least for a couple of years, that’s a benefit”, said Dr. Lageman.

 

Mood and Sociability Presented at the 2013 Parkinson’s World Conference

Susan Spear Bassett, Ph.D. from Johns Hopkins spoke at her poster presentation about depression and social involvement in PARKINSON’S DISEASE.  She and her colleagues conducted a study with 101 people with PARKINSON’S DISEASE who did not have dementia to examine the changes in social function caused by the disease.  They found that cognitive impairments along with depression contributed more to social withdrawal than the motor or movement symptoms of PARKINSON’S DISEASE.  Depression, loss of verbal skills and loss of fine motor skills all contributed to loss of social function, but management of depression did more to improve the quality of life and help social involvement.

 

Falls, Cognition and Gait Presented at the 2013 Parkinson’s World Conference

What are the factors that increase the likelihood that people newly diagnosed with PARKINSON’S DISEASE will fall frequently?   Lynn Rochester, Ph.D. and her team enrolled 94 newly diagnosed people with PARKINSON’S who had never fallen. and followed them for a year.  They wanted to know why some people fall more frequently than others.  Subjects were asked to keep a diary of their falls and underwent testing in several domains over the course of the study.  Findings showed that gait was of major importance.  Step time, speed, and distance of steps as well as the thinking about walking were major predictors of falling.  People who had fallen several times also had less confidence in their ability.  Measurement scales included the Unified Parkinson’s Disease Rating Scale, and the Postural Instability and Gait Disorder that is a sub-scale of the UPDRS, the Hoehn and Yahr Progression Scale, Strength ratings and several cognitive testing scales.  Work for this abstract was done at Newcastle University in Newcastle upon Tyne, England.

 

Parkinson Research Foundation’s Parkinson Place
Parkinson Place - Good Days Start Here
Parkinson Place started in September of 2012 has implemented many of the programs discussed at Montreal and more!  If you want to get a taste of what is going on at Parkinson Place please visit the website www.parkinsonplace.org.  The mission of the Parkinson Research Foundation is to assist in finding a cure for Parkinson’s disease and improving the lives of those living with the disease right now.  Parkinson Place is a Pilot project that has proved very successful creating a one stop shop for everything you need to live well with Parkinson’s.  Many support groups are now starting a “place” of their own using the format and videos from the site.  Come see why we are smiling at Parkinson Place!

 

All abstracts are from the World Parkinson Congress, Montreal, Quebec, Canada.

3.  Gaina, B. et al “motor, cognitive and affective characteristics of new fallers compared to non-fallers in an incident cohort of Parkinson’s disease” WPC 2013 Abstract 13:05

2.  Bassett, S. et al, “Impact of Parkinson’s disease on social role function: multifaceted disability” WPC 2013

1. Lageman, S. et al; “Initial Results of a randomized clinical trial comparing a neurocognitive intervention to supportive therapy in individuals with Parkinson’s disease” WPC 2013; Abstract 15:11

PARKINSON’S DISEASE and Depression

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Two new research studies focused on PARKINSON’S DISEASE and Depression were published recently.  One studies the increased risk of developing PARKINSON’S DISEASE after bouts of treatment resistant depression.  The second study was an analysis of several studies of antidepressant medications used in PARKINSON’S DISEASE.

Depression is a serious risk in people with PARKINSON’S DISEASE; some studies have shown that as many as 60% of people with PD are depressed..  The first study looked at 10 years of records and found correlations between age of onset of depression and development of PD.  In younger patients, depression did not always lead to PARKINSON’S DISEASE, however more senior patients were twice as likely to be diagnosed and seniors whose depression did not respond to treatment were found to be three times more likely to develop  PD.

While this study is not proof-positive that depression necessarily leads to PARKINSON’S DISEASE,  the correlation does bear serious weight for future research.  It may be that depression could be an early symptom or biomarker, like loss of the sense of smell; but since 60% of people with PARKINSON’S report feeling depressed,  it may simply be a symptom.  One limitation of this study was that the population studied did not provide any information about family history or other environmental factors.  These factors will need careful evaluation in future studies.

The second study examined the effects of common antidepressant  treatment in PARKINSON’S DISEASE.  They based their study on 11 clinical trials of treatment for depression in Parkinson’s disease held between 1986 and 2013.  These trials used medications that are standard treatment for depression in PD as well as standard treatments for PD that have shown efficacy for treating depression.  These medications included Tricyclic Antidepressants (TCAs),  Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitore (SNRIs) and Dopamine agonists, which have also been promoted as relieving depression in PD.

The research was very thorough, examining not only the effect on depression, but also on troublesome side effects, such as nausea, dry mouth, headache, dizziness, hallucinations, somnolence and excessive dyskinesias.  They also compared the rating scales used to evaluate depression.  Their basic findings were that dopamine agonists were no more effective than placebo in relieving depression, and sometimes had more serious side effects.  SSRIs and SNRIs  were used as a first choice to avoid the side effects of tricyclic antidepressants, such as dry mouth, dry eyes and constipation.

Ultimately, it was found that tricyclic antidepressants were more effective than SSRis or SNRIs, and were often very well tolerated, suggesting that tricyclic antidepressants might well be a better first choice for depression in PD.

The authors caution that this study has several serious limitations, such as the age of the participants and the stage of the disease.  Motor fluctuations and other co-morbidities and medications also need to be accounted for.  Larger studies are needed to clarify and confirm the data that this early study has begun.

 

  1. C.-C. Shen, S.-J. Tsai, C.-L. Perng, B. I.-T. Kuo, A. C. Yang.Risk of Parkinson disease after depression: A nationwide population-based studyNeurology, 2013; DOI:10.1212/WNL.0b013e3182a956ad

 

  1.  Liu J, Dong J, Wang L, Su Y, Yan P, et al. (2013) Comparative Efficacy and Acceptability of Antidepressants in Parkinson’s Disease: A Network Meta-Analysis. PLoS ONE 8(10): e76651. doi:10.1371/journal.pone.0076651

 

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Alpha-synuclein Under Your Skin???

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Alpha-synuclein has been the subject of so many articles, it does seem to get “under your skin”, so to speak!  Now a research team from Beth Israel Deaconess Medical Center in Boston has found that the alpha-synuclein found just under the skin may be a potent biomarker for PARKINSON’S DISEASE.  Non-motor symptoms such as changes in body temperature, bowel habits, and skin coloration often occur long before other symptoms that lead to the diagnosis of PARKINSON’S DISEASE.  Finding a way to know who is at risk to develop PARKINSON’S DISEASE early in the process could enable earlier treatment and delay onset of the disease, or possibly lead to finding a cure.  This is the search for a biomarker, and it is the basis of many current studies.

Dr. Roy Freeman and his team are one group involved in this search.  Their research has focused on autonomic and peripheral nervous functions in PARKISON’S DISEASE, so they naturally looked at autonomic skin functions and reactions in this disease.  They surmised that a skin biopsy might provide information that could identify a biomarker for PARKINSON’S DISEASE.  In a small study funded by a grant from the National Institutes of Health (NIH) they examined 20 people with a diagnosis of PARKINSON’S DISEASE and 14 non-Parkinsonian controls.  They took skin biopsies from three different locations on their legs and found … alpha-synuclein.  Even higher levels of alpha-synuclein were found in the skin biopsies of people in more advanced stages of PARKINSON’S DISEASE.

The next steps in this study will be to measure alpha-synuclein in skin of people known to be at risk for PARKINSON’S DISEASE, and to see if depositions of alpha-synuclein in the skin can differentiate PARKINSON’S DISEASE from other neurodegenerative diseases.  A small skin biopsy is a safe and simple procedure that could be a big breakthrough as a biomarker to predict PARKINSON’S DISEASE.

Article by Marcia McCall

N. Wang, C.H.Gibbons, J. Lafo, R. Freeman. Synuclein in cutaneous autonomic nerves. Neurology, 2013; DOI 10.1212/WNL.0b013e3182a9f449  

 

 

Competitiveness and Impulsivity Heightened after DBS of Sub-Thalamic Nucleus

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A detailed and very interesting study published this week in the journal Brain is the work of several German and Canadian doctors who focused on personal and social implications of people with PARKINSON’S DISEASE who had undergone deep brain stimulation (DBS) of the sub-thalamic nucleus (STN).  While the DBS offers marked improvements in motor function that definitely improves the quality of life from a movement perspective, many of these people report serious struggles with social and work related problems.  Aspects of a behavioral and social nature are rarely studied in relation to DBS treatment.

The researchers noted that while DBS of sub-thalamic nucleus (STN) is beneficial for motor symptoms, the region stimulated also affects areas of decision making and impulsivity.  This may have the effect of making these people feel over confident and encourages risk-seeking behaviors.  Parkinson Disease sufferers may or may not be aware of this shift in their impulsivity but it may be the basis for some of their personal and work related issues. The researchers hypothesized that DBS-STN causes a pathological change in the way self estimation is perceived in competitive situations.

In order to analyze the self awareness of Parkinson’s disease patients who had had DBS of STN, they used an experiment from behavioral economics that consisted of addition of a long string of numbers.  Groups tested consisted of people with PARKINSON’S DISEASE who had received DBS of Sub-Thalamic Nucleus, people with PARKINSON’S DISEASE who had not received DBS of Sub-Thalamic Nucleus, and non-Parkinsonian controls.  There were four sets of numbers with varying rewards, paired as low risk/low reward, low risk/high reward, to high risk/high reward..  Further, as the subjects progressed from one set to the next, they were asked to estimate their accuracy, and then to choose whether to accept a nominal “prize” or to continue on to a “tournament”.  In all the sets, the controls had the highest accuracy and the DBS-STN the lowest.  As they progressed, the DBS-STN had higher predictions of their accuracy, even though past performance was negative.  26% of the DBS-STN consistently chose high risk/high reward even though based on past performance this was not to their benefit.

This study generated data on many areas of performance and behavior.  One area examined the risk taking behavior of the DBS of Sub-Thalamic Nucleus group compared to the non DBS group.  While very similar in symptoms and length of disease, the non DBS group was less inclined to risk taking behavior leading the researchers to surmise that perhaps there was an inherent bias toward risk taking behavior in the DBS-STN group that perhaps lead them to undergo the potentially risky, invasive DBS surgery in the first place.

In conclusion, the study authors suggest that while the DBS of Sub-Thalamic Nucleus subjects are impaired in their self-estimation, they may naturally have a preference for competitive situations, but that the DBS-STN has impaired the pathways used to evaluate both their decision making skills and the risks involved.  This may help explain some of the social difficulties this population experiences in their work, social and personal lives.

 

E. Florin, D. Muller, J. Pfeifer, M. T. Barbe, G. R. Fink, L. Timmermann; Subthalamic stimulation modulates seslf–estimation of patients with Parkinson’s disease and induced risk-seeking behavior; Brain (2013) doi: 10.1093/brain/awt241 pub 9/25/2013

Stem Cell Transplantation Shows Promise for PARKINSON’S DISEASE

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Many studies going back many years have investigated the possibility of creating neural stem cells in the lab and transplanting them to regions of the brain damaged by PARKINSON’S DISEASE.  Usually, these studies have been done using mouse models of PD and have involved heavy uses of immunosuppression.  Some studies have used cells obtained from the transplanted mouse itself, but results have rarely shown any benefit and are very difficult to duplicate.

Now, a researcher at Kyoto University’s Center for IPS Cell Research and Application in Japan has experimentally shown that cells derived from the subject’s own body produced almost no immune response when transplanted into the brains of monkeys and actually resulted in viable neural cells.  Doctors Jun Takahashi and Asuka Morizane are interested in promoting new neural pathways to restore dopaminergic cell function in the hope that this approach will help people with PARKINSON’S DISEASE.

When cells are obtained from the subject’s own body, they are called autologus.  Cells derived from other sources are called allergenic and evoke a very strong rejection response from the subject that receives them.  Autologus transplants are generally better tolerated especially in those with Parkinson’s disease.  This study used cells derived from the blood of the donor/subject and grew them into induced pluripotent stem cells (iPSC), which were then differentiated into dopaminergic neural cells.  These same cells were then transplanted back to the monkeys’ brain.  The monkeys were observed for three months and not given any immunosuppressant drugs.   No rejection response was seen and the cells became viable, functioning dopaminergic cells in their new location.

This is a radical approach that shows promise, however much more research will be necessary before it can be translated to human applications.

Credits:

“A direct Comparison of Autologus and Allergenic Transplantation of iPSC-Derived Neural Cells in the Brain of a Nonhuman Primate” Stem Cell Reports, 2013. dx.doi.org/10.1016/j.stemcr.2013.08.007

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