patrick.net

https://blog.cirm.ca.gov/2017/09/07/hearts-and-brains-are-center-stage-at-cirm-patient-advocate-event/
Latest Parkinson research.
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Cell replacement may play an increasing role in alleviating the motor symptoms of Parkinson's disease (PD) in future. Writing in a special supplement to the Journal of Parkinson's Disease, experts describe how newly developed stem cell technologies could be used to treat the disease and discuss the great promise, as well as the significant challenges, of stem cell treatment.

The most common PD treatment today is based on enhancing the activity of the nigro-striatal pathway in the brain with dopamine-modulating therapies, thereby increasing striatal dopamine levels and improving motor impairment associated with the disease. However, this treatment has significant long-term limitations and side effects. Stem cell technologies show promise for treating PD and may play an increasing role in alleviating at least the motor symptoms, if not others, in the decades to come.

"We are in desperate need of a better way of helping people with PD. It is on the increase worldwide. There is still no cure, and medications only go part way to fully treat incoordination and movement problems," explained co-authors Claire Henchcliffe, MD, DPhil, from the Department of Neurology, Weill Cornell Medical College, and Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; and Malin Parmar, PhD, from the Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund, Sweden. "If successful, using stem cells as a source of transplantable dopamine-producing nerve cells could revolutionize care of the PD patient in the future. A single surgery could potentially provide a transplant that would last throughout a patient's lifespan, reducing or altogether avoiding the need for dopamine-based medications."

The authors have analyzed how newly developed stem cell technologies could be used to treat PD, and how clinical researchers are moving very quickly to translate this technology to early clinical trials. In the past, most transplantation studies in PD used human cells from aborted embryos. While these transplants could survive and function for many years, there were scientific and ethical issues: fetal cells are in limited supply, and they are highly variable and hard to quality control. Only some patients benefited, and some developed side effects from the grafts, such as uncontrollable movements called dyskinesias.

Recent strides in stem cell technology mean that quality, consistency, activity, and safety can be assured, and that it is possible to grow essentially unlimited amounts of dopamine-producing nerve cells in the laboratory for transplantation. This approach is now rapidly moving into initial testing in clinical trials. The choice of starting material has also expanded with the availability of multiple human embryonic stem cell lines, as well as the possibilities for producing induced pluripotent cells, or neuronal cells from a patient's own blood or skin cells. The first systematic clinical transplantation trials using pluripotent stem cells as donor tissue were initiated in Japan in 2018.

"We are moving into a very exciting era for stem cell therapy," commented Dr. Parmar. "The first-generation cells are now being trialed and new advances in stem cell biology and genetic engineering promise even better cells and therapies in the future. There is a long road ahead in demonstrating how well stem cell-based reparative therapies will work, and much to understand about what, where, and how to deliver the cells, and to whom. But the massive strides in technology over recent years make it tempting to speculate that cell replacement may play an increasing role in alleviating at least the motor symptoms, if not others, in the decades to come."

"With several research groups, including our own centers, quickly moving towards testing of stem cell therapies for PD, there is not only a drive to improve what is possible for our patients, but also a realization that our best chance is harmonizing efforts across groups," added Dr. Henchcliffe. "Right now, we are just talking about the first logical step in using cell therapies in PD. Importantly, it could open the way to being able to engineer the cells to provide superior treatment, possibly using different types of cells to treat different symptoms of PD like movement problems and memory loss."

"This approach to brain repair in PD definitely has major potential, and the coming two decades might also see even greater advances in stem cell engineering with stem cells that are tailor-made for specific patients or patient groups," commented Patrik Brundin, MD, PhD, Van Andel Research Institute, Grand Rapids, MI, USA, and J. William Langston, MD, Stanford Udall Center, Department of Pathology, Stanford University, Palo Alto, CA, USA, Editors-in-Chief of the Journal of Parkinson's Disease. "At the same time, there are several biological, practical, and commercial hurdles that need circumventing for this to become a routine therapy."

https://www.sciencedaily.com/releases/2019/02/190214153141.htm

@curious2

Not sure if you are/were aware of this Medical Journal, "The Journal of Parkinson's Disease" which is cited in the first paragraph.

Here is the link: https://www.journalofparkinsonsdisease.com/

Kakistocracy says

"The Journal of Parkinson's Disease"

That journal (and others) describes a great, short summary on the possible links between gut and brain wrt Parkinson's:

"More and more studies are suggesting that the condition starts in the gastrointestinal system — at least for some people who have digestive symptoms years before any motor symptoms develop.

Some studies have even shown that the alpha-synuclein protein, which is abnormal in Parkinson's disease, travels from the brain to the stomach via the vagus nerve, a major component of the parasympathetic nervous system."

The summary contains links, including to this article from Finland:

"In the last two decades it has become clear that Parkinson’s disease (PD) is associated with a plethora of gastrointestinal symptoms originating from functional and structural changes in the gut and its associated neural structures. This is of particular interest not only because such symptoms have a major impact on the quality of life of PD patients, but also since accumulating evidence suggests that in at least a subgroup of patients, these disturbances precede the motor symptoms and diagnosis of PD by years and may thus give important insights into the origin and pathogenesis of the disease. In this mini-review we attempt to concisely summarize the current knowledge after two decades of research on the gut-brain axis in PD."

Cell transplant research is very interesting, whether IPS or fetal cells, but past attempts with fetal cells showed Parkinson's could return. I suspect that recurrence in some cases might result from residual prions traveling up the vagus nerve, or continued exposure to whatever dietary or other environmental sources caused the problem.

Parkinson's subtyping will likely illuminate significant differences between genetic, dietary, and other environmental exposures. Stem cells might work well in purely genetic cases, but the others might require addressing the environmental factors to prevent recurrence.

curious2 says

when R's are in charge, they call stem cell research "immoral" (though they launch phony wars killing thousands of people including children)

Democrats are responsible for starting, if not more wars than at least as many wars as Republicans:

WWI Woodrow Wilson

WWII FDR

Korean war Eisenhower

Vietnam war Kennedy/Johnson

Middle East conflict Bush, continued under Obama

Trump is trying to end the Middle East conflict

If Democrats did not start more wars, you can say they are at least just as culpable.

This thread is about Parkinson's Disease research.

@curious2

'Super-smeller' helps develop swab test for Parkinson's disease - Distinctive musky odour of people with Parkinson’s could lead to earlier diagnosis

Scientists have developed a test for Parkinson’s disease based on its signature odour after teaming up with a woman who can smell the condition before tremors and other clinical symptoms appear.

The test could help doctors diagnose patients sooner and identify those in the earliest stages of the disease, who could benefit from experimental drugs that aim to protect brain cells from being killed off.

Perdita Barran, of the University of Manchester, said the test had the potential to decrease the time it took to distinguish people with normal brain ageing from those with the first signs of the disorder. “Being able to say categorically, and early on, that a person has Parkinson’s disease would be very useful,” she said.

Most people cannot detect the scent of Parkinson’s, but some who have a heightened sense of smell report a distinctive, musky odour on patients. One such “super smeller” is Joy Milne, a former nurse, who first noticed the smell on her husband, Les, 12 years before he was diagnosed.

Milne only realised she could sniff out Parkinson’s when she attended a patient support group with her husband and found everyone in the room smelled the same. She thought little more about it until she mentioned the odour to Tilo Kunath, a neurobiologist who studies Parkinson’s at Edinburgh University.

Kunath tested Milne’s skills by having her sniff T-shirts worn by either healthy people or Parkinson’s patients. Milne identified all those worn by the patients and said one more T-shirt bore the same scent. Eight months later, the wearer was diagnosed with the disease.

For the latest study, Barran worked with Kunath and Milne to identify the main substances that give rise to the distinctive Parkinson’s odour. They focused on compounds in sebum, a waxy fluid that is secreted by glands in the skin, particularly on the upper back where Milne said the scent was strongest.

The scientists used a technique called mass spectrometry to measure levels of volatile chemicals in sebum on swabs from Parkinson’s patients and healthy volunteers. By testing different groups, they whittled down the number of fragrant compounds from thousands to just four that appear to be most important for the scent.

Writing in the journal ACS Central Science, the researchers describe how Milne confirmed that mixtures of the four compounds had the same musky smell as Parkinson’s patients. Tests found that levels of three substances, eicosane, hippuric acid and octadecanal, were all higher than normal in the sebum of Parkinson’s patients, while levels of a fourth substance, perillic aldehyde, were lower.

To see whether the test can spot Parkinson’s before doctors can, the scientists have teamed up with researchers in Austria who study people with REM sleep disorders. A separate study found people with a specific kind of such disorder have a 50% risk of developing Parkinson’s in later life.

“If we can detect the disease early on, that would be very good news. It would mean we have a test that picks it up before motor symptoms appear,” Barran said.

In parallel, more than 1,000 Parkinson’s patients and hundreds of healthy people will have their sebum analysed to see how reliable the test is. Scientists will also look at whether changes in the odour reflect the progression of the disease, or even different forms of Parkinson’s.

Werner Poewe, the director of neurology at the Medical University of Innsbruck, said diagnosing Parkinson’s early and accurately was critical to giving patients the best advice and treatment. The discovery of a Parkinson’s scent “opens up an entirely new approach to test for the presence of Parkinson’s by a non-invasive test that only involves swabbing a piece of gauze across the neck region of a patient,” he said.

“Identifying [early] stages of the disease in those who have not yet developed classical signs and symptoms of Parkinson’s disease is a necessary first step to eventually testing new treatments that will delay or prevent the onset of this illness,” Poewe added.

Milne, whose sense of smell is so sensitive she has to avoid the more fragrant aisles of supermarkets, has identified the scents of other diseases too. To her, Alzheimer’s smells vaguely of vanilla, while cancer has a more earthy odour. In her next collaboration with the Manchester group, the aim will be to identify chemicals that produce a signature odour for tuberculosis.

https://www.theguardian.com/society/2019/mar/20/super-smeller-helps-develop-swab-test-for-parkinsons-disease

NOTE: This next link is much better and has access to the PDF for the study cited above.
https://pubs.acs.org/doi/10.1021/acscentsci.8b00879

@curious2 - possibly of some interest to you.

New treatment may slow, stop, reverse Parkinson's disease. Researchers have developed a new drug that could correct damage to the brain caused by Parkinson's disease and lead to improvement of symptoms, researchers report.

Patients who had implants to replace damaged brain cells showed 100 percent improvement in reawakening portions of their brains harmed by Parkinson's, according to research published Tuesday in the Journal of Parkinson's Disease.

"The spatial and relative magnitude of the improvement in the brain scans is beyond anything seen previously in trials of surgically delivered growth-factor treatments for Parkinson's," Alan L. Whone, a researcher at University of Bristol and study author, said in a news release. "This represents some of the most compelling evidence yet that we may have a means to possibly reawaken and restore the dopamine brain cells that are gradually destroyed in Parkinson's."

The researchers used robot-assisted neurosurgery to implant a special delivery system to release Glial Cell Line-Derived Neurotrophic Factor into the brain cells of Parkinson's patients.

More: https://www.upi.com/Health_News/2019/02/27/New-treatment-may-slow-stop-reverse-Parkinsons-disease/8751551281589/

@curious2 - possibly of some interest to you.

Number of people with Parkinson's may double in 20 years, report says - In a report warning of a possible Parkinson's "pandemic," researchers say the stage is set for cases to surge to 12 million or more by 2040.

The number of people living with Parkinson's disease worldwide could double in the next two decades, experts project.

In a report warning of a possible Parkinson's "pandemic," researchers say the stage is set for cases to surge to 12 million or more by 2040.

What's to blame? In large part, trends that are generally positive: Older age is a major risk factor for Parkinson's, and with life expectancy rising worldwide, more people will develop the disease. At the same time, Parkinson's patients are surviving longer, which drives up the number of people living with the disease at any given time.

Then there's a less expected factor: Declining smoking rates. While the habit has many devastating effects, research suggests it protects against Parkinson's

More: https://www.upi.com/Health_News/2019/02/19/Number-of-people-with-Parkinsons-may-double-in-20-years-report-says/1751550591755/

@curious2 - possibly of some interest to you.

Parkinson's gene therapy may reduce medicine required for treatment

March 21 (UPI) -- A new brain operation may reduce the severity of motor problems in people with Parkinson's disease and decrease the amount of medication they need, a new study says.

This treatment helped Parkinson's patients reduce their medication by up to 42 percent, according to findings published Wednesday in the Annals of Neurology.

It also gave patients three extra hours a day of "on-time," the period where medication doesn't cause involuntary muscle movements. This condition is a common side effect called dyskinesia, which is brought on due to long-term medication use.

"This is the first gene therapy trial for Parkinson's disease trial in which intra-operative MRI-guided monitoring was used," Chad Christine, a researcher at the University of California at San Francisco Department of Neurology and study first author, said in a news release. "This allowed us to visualize and guide the infusion of the treatment into the brain in real time, to ensure delivery to the area that should provide maximum benefit."

The researchers developed a method of gene therapy for increasing an enzyme called AADC, which converts the drug into dopamine. Using an inactive virus, the researchers injected the gene into a part of the brain called the putamen.

Group one saw 1.6 hours of on-time and a 15 percent reduction in medicine, while group two got 3.3 hours and a 33 percent reduction in medicine. Group three got 1.5 hours on-time and a 42 percent reduction in drugs.

"We have evidence from a previous study that the gene therapy results in stable expression of the AADC enzyme," Christine said. "We believe that this treatment will allow these patients to more efficiently convert levodopa into dopamine, thereby obtaining greater improvements in mobility with each dose. Since many patients were able to substantially reduce the amount of Parkinson's medications, this gene therapy treatment may also help patients by reducing dose-dependent side effects, such as sleepiness and nausea."

More: https://www.upi.com/Health_News/2019/03/21/Parkinsons-gene-therapy-may-reduce-medicine-required-for-treatment/5211553170330/