patrick.net

mell says

Ampakines are considered a compound of interest, also for many other indications, generally improving memory functions, but research and drug development seems to be crawling along at snails pace there as well. Piracetam is a weak one (which you can get as a supplement)

Thanks mell :)

I found links showing interest in ampakines, and links to online retailers. Unfortunately, I have not yet found any published studies or results.

Meanwhile, I've been finding providers of stem cell technology, including an SF company:

http://sfstemcellcenter.com/stem-cell-treatment/

I haven't yet found data to evaluate results though.

BTW, although Google News can be the most current way to see the most recently updated stories, it suffers from a commercial bias, manipulated by publicists and public relations (PR) campaigns. Just as Google search spawned a search engine optimization (SEO) industry, Google News has apparently done likewise for the PR industry. I've been reading about Parkinson's and Google News alerted me to a widely reported study that said Parkinson's patients improve more with expensive placebos than cheap ones; the sample size turned out to be 12 patients. The study authors note that it provides "Class III evidence," i.e. the lowest of any type of study other than Internet surveys and phoning an expert, but it made headlines almost simultaneously throughout the commercial press. I am guessing the PR campaign to push the study cost probably 100x more than the study itself, and who knows how many studies of the same size found no effect at all before one turned up saying higher costs confer medicinal benefit. Seeing the glass half-full, I suppose these campaigns were happening long before Google arrived, and now Google News makes obvious the "invisible hand" that had previously been hidden.

Also, if this Parkinson's Disease thread gets the attention of anyone affiliated with California biotech companies, they might want to know that as of November CIRM still had $1 billion to invest and expressed interest in co-funding with industry and investors its $3 billion under Proposition 71. Consistent with the OP at the start of my reading, I have found distressingly little federal funding, but considerable funding at the California state level and from industry and private charities (e.g. the Michael J. Fox Foundation).

curious2 says

Google News has apparently done likewise for the PR industry. I've been reading about Parkinson's and Google News alerted me to a widely reported study that said Parkinson's patients improve more with expensive placebos than cheap ones; the sample size turned out to be 12 patients

Have you thought about using Duck Duck Go? It'll spread the search out, over the various search engines w/o revealing you, and then, it's harder for them to profile their ads towards you?

Thanks Rin, I've been using DuckDuckGo since Patrick mentioned it. I'm not worried about ads, but I do feel somewhat uncomfortable about Big Brother's "Total Information Awareness" combined with "Total Recall." I was fascinated by reports on "60 minutes" about superior memory, including considerable evidence that the ability to forget may be evolutionarily adaptive. I think the EU has a point regarding "the right to be forgotten", though I don't blame the search engines. Many Facebook users report that disclosing their opinions caused them to lose friends, for example. As a species, we have no evolutionary history of "Total Information Awareness" and "Total Recall", and we see many examples where seemingly banal information found online caused serious consequences IRL.

I use a combination of VPN, DuckDuckGo, and Disconnect for privacy.

As for social media, I'd completely rejected it because the way I see it, it's fertile grounds for ID theft.

I created a thread for the sf tech companies involved, but the report merits a comment here too:

"Genentech, 23andMe ink $60 million Parkinson's disease research deal
***
The deal, announced Tuesday, will tap whole genome sequencing data for about 3,000 people in 23andMe's database, including those who have been diagnosed with Parkinson's, a progressive, nervous system disorder that is tagged in more than 50,000 Americans annually. Consenting immediate family members of Parkinson's patients also will be included in the study."

Along with the comments about things that might hopefully work someday, I should probably post this report about something that doesn't work: Creatine monohydrate.... Previous research in mice suggested that creatine supplements might potentially protect nerve cells.
***
The new study included more than 1,700 people in the United States and Canada who had been diagnosed with Parkinson's disease within the previous five years. All were receiving treatment for Parkinson's disease. As part of the study, they were randomly assigned to take creatine or a placebo in addition to their usual treatment.

The patients were enrolled from March 2007 to May 2010 and followed up until September 2013. The study was halted early because those taking creatine showed no differences in disease progression compared to those taking the placebo."

In slightly better news, small studies suggest a new breath test for VOCs might become the first definitive test to diagnose Parkinson's Disease. Researchers are preparing larger studies.

Also in possibly better news, a daily beer may reduce the risk of developing Parkinson's and Alzheimer's diseases.

Today's NY Times reports on additional research: An American biotech company [in Cambridge, MA], NeuroPhage, for example, plans to enroll Alzheimer’s and Parkinson’s patients in 2016 and 2017 in Phase 1 trials of its new product, a genetically engineered compound derived from a naturally occurring virus called M13. Researchers have demonstrated that this compound can enter rodents’ brains and neutralize toxic clumps of alpha-synuclein and the corresponding targets for Alzheimer’s (the proteins amyloid beta and tau).

A Roche and Prothena collaboration Phase 1 trial Reports Reduction of Free Serum Alpha-Synuclein After Single Dose of PRX002. Roche is the parent company of SFBA's Genentech, a large biotech company based in South San Francisco.

From Brazil: "Mitomycin-treated undifferentiated embryonic stem cells as a safe and effective therapeutic strategy in a mouse model of Parkinson’s disease"

"Barker and many other researchers say toxins get taken up in the bowels of patients and that over the years these are slowly transported to the central nervous system until they become lodged in some of the cells of the brain. There, they ultimately wreak damage to cells of the mid-brain, where dopamine, a neurotransmitter involved in motor control, is made.

Prions were first proposed to be the causes of fatal brain diseases such as Creutzfeldt-Jakob in the 1980s, and have since been linked to a number of conditions affecting humans and animals... As to the identity of the protein transformed in Parkinson’s, the main candidate is alpha-synuclein, which is found in the brain, though its function is unclear. Recent research suggests it could be transformed into an abnormal state and play a key role in development of Parkinson’s."

The article reports on vaccine research already linked above, and fetal VM transplants where the transplanted tissue also developed Parkinson's.

Rin says

How about using pre-existing adult stem cells, to re-generate the substantia nigra, the section of the brain damaged by Parkinson's?

Because you'll give them paranoid schizophrenia?

Regarding the isradipine Phase III trial linked above, the study should last three years. I tried to edit the original comment but couldn't for some reason.

Notable mouse research at The Buck Institute, an SFBA research facility:

"Lithium may help halt progression of Parkinson's"

"Low-Dose Lithium Reduces Side Effects From Most Common Parkinson’s Disease Treatment"

It's a long way from a mouse to a human, but interesting nonetheless.

Notable mouse research at UNC:

"The researchers [at the University of North Carolina at Chapel Hill] genetically modified white blood cells called macrophages to produce glial cell–derived neurotrophic factor, or GDNF, and deliver it to the brain. Glial cells provide support and protection for nerve cells throughout the brain and body, and GDNF can heal and stimulate the growth of damaged neurons.
***
In addition to delivering GDNF, the engineered macrophages can “teach” neurons to make the protein for themselves by delivering both the tools and the instructions needed: DNA, messenger RNA and transcription factor... Using immune cells avoids the body’s natural defenses. The repurposed macrophages are also able to penetrate the blood-brain barrier, something most medicines cannot do. The reprogrammed cells travel to the brain and produce tiny bubbles called exosomes that contain GDNF. The cells release the exosomes, which then are able to deliver the proteins to neurons in the brain."

Full article on PLOS One:

"GDNF-Transfected Macrophages Produce Potent Neuroprotective Effects in Parkinson's Disease Mouse Model"

Three updates:

“NeuroPhage in Cambridge, Mass., is based on a simple virus called M13. This product may be able to reduce the amounts of...alpha-synuclein....”

“coffee has protective qualities against...Parkinson’s disease... drinking four or five cups of coffee daily cut risk of developing Parkinson’s Disease nearly in half compared with little or no caffeine consumption.”

"A pilot study of 12 patients given small doses of nilotinib found that movement and mental function improved in all of the 11 people who completed the six-month trial, researchers reported Saturday at the Society for Neuroscience meeting in Chicago."

"Edward Burton, MD, FRCP, Associate Professor of Neurology at the University of Pittsburgh School of Medicine is among a team of researchers working on a way to slow down the progression of the disease.

Dr. Burton says the finding could lead to new drugs to protect the brain from neurodegeneration.
***
Dr. Burton says a clinical trial of gene therapy in humans is only 2-3 years away."

"Biotechnology company International Stem Cell Corp. (ISCO) is authorized by the Australian government to conduct a clinical trial in patients with moderate to severe Parkinson's disease. The company's subsidiary, Cyto Therapeutics, received regulatory approval from the Therapeutics Goods Administration (TGA) of Australia.

In Cyto's future Phase I/IIa clinical trial, doctors will be able to insert replacement brain cells called neural precursor cells into 12 patients."

"Pioneering Neuroprotective Results Achieved in Parkinson's Disease Preclinical Studies Allows immune system to repair brain damage; results reported in Journal of Neuroscience

A team of scientists at the University of Nebraska Medical Center (UNMC) and Longevity Biotech, Inc. demonstrated that neuroprotection could be attained in preclinical models by a novel drug candidate that changes immune responses. The results, published today in the Journal of Neuroscience, describe the prevention of nerve cell damage in a mouse model of Parkinson's disease. Notably, the drug protected nerve cells that produce dopamine, which is the chemical responsible for agility and movement that is lost in human disease.
***
The new Longevity Biotech drug (LBT-3627) was able to change the function of these cells from killing the nerve cells to protecting them. This is especially significant for the Nebraska team, as the mechanism parallels closely the human trials nearing completion for Parkinson's patients."

I had previously commented on NeuroPhage a year ago, and they seem to be moving ahead on the schedule they had announced then:

"The Virus That Could Cure Alzheimer’s, Parkinson’s, and More
***
The phage M13’s goal is to infect just one type of bacteria, Escherichia coli, or E. coli, which can be found in copious amounts in the intestines of mammals. Like other microorganisms, phages such as M13 have only one purpose: to pass on their genes. In order to do this, they have developed weapons to enable them to invade, take over, and even kill their bacterial hosts. Before the advent of antibiotics, in fact, doctors occasionally used phages to fight otherwise incurable bacterial infections.
***
Immunotherapy employs specially made antibodies, rather than small molecule drugs, to target the disease’s plaques and tangles. As high school students learn in biology class, antibodies are Y-shaped proteins that are part of the body’s natural defense against infection. These proteins are designed to latch onto invaders and hold them so that they can be destroyed by the immune system. But since the 1970s, molecular biologists have been able to genetically engineer human-made antibodies, fashioned to attack undesirable interlopers like cancer cells.
***
the phage’s special abilities involved a set of proteins displayed on the tip of the virus, called GP3.
***
By 2013, NeuroPhage’s researchers had tested the new compound, which they called NPT088, in test tubes and in animals, including nonhuman primates. It performed spectacularly, simultaneously targeting multiple misfolded proteins such as amyloid beta, tau, and alpha-synuclein at various stages of amyloid assembly.
***
The concept is that this antibody could be administered to patients once or twice a month by intravenous infusion for as long as necessary.
***
NeuroPhage must now navigate the FDA’s regulatory system and demonstrate that its product is safe and effective. So far, NPT088 has proved safe in nonhuman primates. But the big test will be the phase 1A trial expected to be under way this year. This first human study proposed is a single-dose trial to look for any adverse effects in healthy volunteers. If all goes well, NeuroPhage will launch a phase 1B study involving some 50 patients with Alzheimer’s to demonstrate proof of the drug’s activity. Patients will have their brains imaged at the start to determine the amount of amyloid-beta and tau. Then, after taking the drug for six months, they will be reimaged to see if the drug has reduced the aggregates below the baseline.

“If our drug works, we will see it working in this trial,” Hillerstrom says. “And then we may be able to go straight to phase 2 trials for both Alzheimer’s and Parkinson’s.”
***
Along the way, the company will have to prove its GAIM system is superior to the competition. Currently, there are several drug and biotech companies testing products in clinical trials for Alzheimer’s disease, against both amyloid-beta (Lilly, Pfizer, Novartis, and Genentech) and tau (TauRx) and also corporations with products against alpha-synuclein for Parkinson’s disease (AFFiRiS and Prothena/Roche). But Solomon and Hillerstrom think they have two advantages: multi-target flexibility (their product is the only one that can target multiple amyloids at once) and potency (they believe that NPT088 eliminates more toxic aggregates than their competitors’ products)."

BTW, I don't know what psycho Disliked three (1, 2, 3) of my comments above, without explanation, but if they have some scientific objection then let them present it. Apparently, (s)he Disliked basically all of my comments over a 20-day period, and is probably some closeted Muslim whom I offended and who tried to take revenge by Disliking everything from Parkinson's research to Don Henley. Meanwhile, this thread combines links to more than 40 relevant research efforts around the world, and thus PatNet provides a more comprehensive reference on this topic than anything else I've found anywhere, with the possible exception of (and certainly Honorable Mention to) the Michael J. Fox Foundation, which finances much of the best research worldwide.

“Hopefully [uncoated graphene] will pave the way for better deep brain implants to both harness and control the brain, with higher sensitivity and fewer...side effects."

Tet3FL “Stopping disruptions in cellular 'trash removal' may guard against neurodegenerative diseases”

Stem cells “Regrowing dopaminergic neurons may lead to new therapy for Parkinson's disease”

“California-based International Stem Cell Corporation (ISCO) set to start clinical trials on 12 people with moderate to severe Parkinson's Disease...doctors will implant replacement brain cells, called neural precursor cells, into the patients' brains. It is hoped these cells will finish maturing into the kind of neurons which are destroyed by the movement disorder. The trials, which are the first to be carried out on humans, will give participants varying doses of neural stem cells. Patients will then have their neurological condition monitored for 12 months to see how their brains and bodies react.”

Dr Oyekpen fucks genetically modified goats and uses the stem cells from the aborted goat-man embryos to formulate cures for various diseases. The snake oil is just a carrier fluid for the active ingredient.

Ironman says

Dan, is that you?

Don't worry ironvagina, I'm sure your goats are organic. Plus, I heard you sucked the semen back out of the goat as a form of birth control.

@Patrick, this thread is veering off topic and into a recurring flame war that has already littered other parts of PatNet. The flames are not commercial Spam, but is there a permissible way to remove them before they hijack the thread? Free speech doesn't benefit from burying the comments about Parkinson's research under a flaming haystack of goat feed.

how about ignoring the people who are in the flame war?

then you won't see them.

i'm trying to maintain a coherent and fair set of beliefs. currently, they are like this:

1. everyone has the right to say whatever the fuck they want on patrick.net, subject only to the 5 disallowed categories as documented in the "about" link:

threats
child porn
spam
copyright violations (upon notice)
personally identifying information

2. everyone also has the right to ignore people they do not want to hear from

Thanks - for a while there was an option for the user who posted a new thread to deleted comments from it, and for a while those comments went to a different thread for deleted comments. I could start Ignoring people but I would miss their other comments. People have strengths and weaknesses, and everyone is imperfect. Ignore vs Unignore seems too binary when talking about something as complex as a person.

allowing deletion of comments felt like it violated belief number 1 above: "everyone has the right to say whatever the fuck they want on patrick.net"

it just seems too much like censorship to actually delete a comment.

rando says

on patrick.net"

Maybe a "move" feature would help, as in "move this comment to a more appropriate thread," e.g. the flame war thread.

ok, maybe it should be possible to mark things as "off topic"

curious2 says

@Patrick, this thread is veering off topic

Sorry I deleted my post, it was half serious btw.

Thanks - I hadn't objected to your comment, which I saw was related to Parkinson's research. Subsequent comments went further astray.

Regarding stem cells, research is moving away from embryonic stem (ES) cells and towards cells grown in laboratories, including induced pluripotent stem (iPS) cells made by scraping adult cells from a patient's skin and inducing them to produce stem cells. The iPS technology was first proved in 2007, and it is now reportedly easier to produce stem cells in a lab than to obtain them from fetal tissue. Meanwhile, studies of patients who had transplants using small needles to the brain have shown the transplanted cells do well, improving patients' symtoms markedly. (Other transplants to the brain had used larger needles, which were less successful. Some providers sell injections to the bloodstream, but they have not yet proved efficacy.) The ES cells were controversial even among patients, so iPS is becoming the new standard.

The iPS technology has huge potential for replacing whole organs, too: within around a decade, a patient needing a new kidney might be able to grow one from his own skin cells.

“Aggregation of α-synuclein contributes to the formation of Lewy bodies and neurites, the pathologic hallmarks of Parkinson disease (PD) and α-synucleinopathies...hyperactivity of the nonreceptor tyrosine kinase c-Abl critically regulates α-synuclein–induced neuropathology...deletion of the gene encoding c-Abl reduced α-synuclein aggregation, neuropathology, and neurobehavioral deficits...selective inhibition of c-Abl may be neuroprotective.”

Patrick,
Comments aren't the problem,it's the commenters. lol