One problem I see with this proposal is that the premise underlying it is based on a sample size of only two. I think the current trial needs to be completed before a new trial such as the one proposed could commence.

As you said recently in another thread, Nan, the main reason the current trial will take so long is a lack of resources, not a lack of volunteers. If there was some way to increase those resources, the end date could surely be brought forward considerably.

As I see it, there is my PD (which may be different to yours) and my response to it (which almost certainly is different to yours). Given this, why focus on increasing n, the sample size? If X works for me, the fact that it doesn't work for you doesn't stop it working for me.

As I see it, what we really need is evidence that the therapy (including any placebo effect) is really working for Nan (taking into account the risks). If it is working, try to continue with the therapy, monitoring your progress, good and bad, as you go. If it stops working for you, then (possibly over a period of time) stop using it.

John

If it only works for a few PwPs, then I would think that it would be too expensive to provide the service. I think that it needs to work for a large number of PwPs. To determine this you would surely need something similar to the current trial(s).

Similar to the current trials, but not the same. Instead of having such a broad range of patients, narrow it down as I suggested in my long post. People who cycle, people who are fit, people whose symptoms are a, b and c. Additionally, I think there should be a compassionate response that would allow someone who experiences relief to continue the treatment as John suggests.

Nan, I don't think it can be narrowed down yet. N equals 2 at present. I think that N needs to equal at least 18 (i.e. the end of the current trial) before any narrowing down takes place.

Regarding the possibility of a compassionate response, I see loads of obstacles to overcome:
- determining who qualifies;
- setting the length of the response;
- getting permission from donors for their plasma to be used in this way;
- setting up the infrastructure, and processes, to support this response;
- securing the funding.

I'm not sure that a young-plasma service for PwPs is even the goal of this research. Maybe if the current trials are successful, the next project will be to find out exactly which component of young plasma is responsible for the improvement(s). Maybe it will only be made available to PwPs if/when it reaches the form of a medication/supplement.

How should we interpret Nan's apparent good response and the other lady's apparent non-response to the treatment?

I don't see either response as conclusive for either party. I see the situation probabilistically. Based on prior experience the two ladies went into the trial with a probability of success. On the basis of the results we have seen, we need to adjust the probability for both. For instance, we may of thought that Nan went into the trial with a probability of success of 0.2, and on the basis of the response so far we need to increase this to 0.5, say. (This approach is called Bayesian.)

We can add to our knowledge by increasing the number of new patients or by increasing the number of data points for existing patients.

There are all sorts of confounding events that could have affected the responses: the type of PD; the placebo effect; and the weather being obvious ones.

I agree with jeffreyn that there's a long list of difficulties that need to be overcome before someone can be allowed to continue with the treatment. But, I don't think that these are insurmountable.

If we want more people to volunteer for trials then we need to make their experience better. A compassionate response should be the least that we can expect.

John

Clearly my response to all of this is the skewed by the fact that it's my body we're talking about. Thanks for bringing more rational perspectives to the table.

I had my last infusion on Valentine's Day and three months later, nearly all the positive benefits are retained. This week I bumped into the Movement Disorder Specialist who diagnosed me nearly 10 years ago and has seen me seldom since. She was flabbergasted at how little I've changed from when she knew me before any PD.

More Than Placebo May 26, 2017

Background In December 2016 I started the Stanford Young Plasma Study. I had eight infusions of blood plasma taken from 18-25 year old males as part of the Phase I study to see if this procedure was safe for humans. As I was the first Parkinson’s patient in the world to have such infusions, no one really knew what to expect. The hope, of course, is that young plasma will somehow be able to mitigate the course of the disease, or perhaps even reverse it. I had three extensive on and off medication batteries of tests, including UPDRS part 3, 1) in January prior to the infusions, 2) after Valentine’s Day at the end of the infusions and then 3) 5.5 weeks later. The PI performed the first round of the off medication testing and then other staff (4 or 5 in all) performed the other tests. We were thrilled that my test scores went from 28 off meds and 13 on meds prior to infusions to 14 off meds and 10 on meds at the end of the infusions and 14 and 7 after 5.5 weeks with no infusions. Infusions? Placebo? Who knows what is going on? I can report that I feel much better in nearly all aspects of my Parkinson’s and the effects continue.

Update This week I traveled to Baltimore for my third year of participation in another Biomarkers research trial, this one at Johns Hopkins. I was more than a little eager to see how I would score on the same UPDRS test at JH. The PI tested me a year ago on the UPDRS and tested me again May 25th. She self-reports as a “hard scorer”. I refused to tell her about Stanford until after she had completed the UPDRS test, now 3.5 months after the infusions. I scored 19. More significantly, she told me that last year I scored 28 using the same test and the same person giving the test, a drop of 9 points! Later she told my husband that when I walked into the office she was startled at how much better I looked from last year.

I think we can safely say that this is more than placebo. So far we have N=1. What is there about me that I respond so strongly to the infusions? Is this a combination of cycling, dance, medicine and infusions or is something else going on here? Questions I can’t answer. I can only be happy and grateful and hope the trial will become available to others soon.

That's a wonderful update, Nan! Thanks for all you do for our community and for all of the trials that you participate in. Let's hope that they move this study along into a larger phase 2 as quick as possible.

Gary

I sound rather like a broken record, but I'm happy to report that my symptoms remain relatively unchanged. Every now and then I experience a mild tremor in my fact, not visible, and I take naps in the afternoon.

Hi Nan,

Don't worry about the broken record, the words that it's repeating are words that we all like to hear.

Just to clarify something, are you saying that your hand/arm tremor has not reappeared, and that the only tremor you have now is a mild tremor in your foot every now and then?

Thanks,
Jeff

It would help if I proofread my posts. The mild tremor is in my face, not my fact or my foot! The hand tremor reappears now and then, not predictable and not even very annoying.

I had foot surgery for hallux rigid (big toe joint) on June 5 and was unable to ride my bike outside until today. I have a Cartiva implant. I rode for 45 minutes, including up two long hills. Other than being sleepier than normal this afternoon, I feel well.

Nan would you recommend the Cartiva Implant for Hallux rigidus. Did you have pain prior to surgery? How is the mobility in your Big Toe post surgery?

Sience my doctorate is in anthropology, i''m not particularly qualified to answer your question. The Cartiva implant has been used in Europe and Canada for 5 plus years but was just recently approved by the FDA. I was the third person in Seattle to have the surgery, all by the same doc. It took the doctor 23 minutes, which tells something about the complexity. Prior to surgery I had been living with arthritis and bone on bone, which was quite painful. The surgery was June 5, about 3 weeks ago. I walked out of the hospital and 11 days later I was no longer using the "boot". I just returned from an hour of fast paced cycling and went 45 min yesterday. My pain is at about a 3. I only needed 5 pills for pain after the surgery, 1.5 day's worth. Mobility is very good. I keep working on it.

This article from The Economist provides a good description of the Stanford Plasma Study. I continue to hold my own for the most part.
https://www.economist.com/news/scien...revitalise-old

Medscape has a recent article that contains some information about the young-plasma trial for AD.

"Human Blood May Offer Fresh Approach for Dementia Treatment", July 27, 2017.

"The next step is to identify and then deliver only those proteins that drive function. The idea is to actually make protein therapeutics or peptides that will recapitulate that function. This ... would avoid the need for plasma donors."

http://search.medscape.com/search/?q...ntia Treatment

(If you are not already a Medscape member, you will need to sign up for a free account)

Please see the Pedaling for Parkinson's thread for an account of my raft trip down the Colorado through the Grand Canyon. Again, the plasma benefits are holding strong. My balance is off and I'm slower but those are about the only negatives.

It's difficult for me to attribute what to what with both toe surgery and knee surgery on the same leg. After an initial positive period with the toe implant, I experienced pretty consistent pain (4), which didn't start to go away until I started doing toe specific PT. I also bought new bike shoes that eliminated pressure points on my foot. I'm hopeful they're good for the long haul.

The plasma results continue to amaze me. I still have no nausea, bowels function normally and I generally feel pretty good, although off sometimes later in the day. My energy level is low and I have had some depression now and then, which seems to be cured now that I'm cycling again. It's hard for me to sit in one place for a long time, flying, movie, play, etc.

On the Clinical Trials website, the "young plasma for PD" trial has an estimated Study Completion Date of December 2018. Unfortunately, I think we can expect to wait another year or two for the research paper(s) to emerge.
The Stanford Parkinson's Disease Plasma Study - Full Text View - ClinicalTrials.gov

Meanwhile, the "young plasma for AD" trial (Study Completion Date: February 2017) has recently published a research paper [1]. The research paper is behind a paywall, but here is an article about it.
Young Fresh Frozen Plasma Proves Feasible for Alzheimer Symptom Amelioration

[1] Sha SJ, Deutsch GK, Tian L, et al. Safety, tolerability, and feasibility of young plasma infusion in the plasma for Alzheimer symptom amelioration study: a randomized clinical trial. JAMA Neurol. epub October 29, 2018. doi: 10.1001/jamaneurol.2018.3288.
Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial. - PubMed - NCBI

Alkahest update
 

Simon has recently done a substantial SoPD blog post on this (and related) research:

From Alchemy to Alkahest | The Science of Parkinson's

Young plasma state-of-play
 

From Simon's SoPD blog post, here is my understanding of the current state-of-play regarding "young plasma for PD".

The clinical trial that Nan_Cyclist took part in (NCT02968433), conducted at the Stanford Movement Disorders Clinic, is now coming to an end.

Independently of this, researchers (from Stanford University and Alkahest) who conducted the earlier "young plasma for AD" trial (NCT02256306), have "distilled" young plasma into an injectable "drug" (GRF6021) that is now being tested in a Phase 2 trial involving 90 volunteers with either PD or PD with mild cognitive impairment (NCT03713957).

An earlier version of the drug (GRF6019), consisting of about 400 proteins, is currently being tested on volunteers with either mild-to-moderate (NCT03520998 ) or severe (NCT03765762) Alzheimer's disease.

For anyone who might be interested, the new PD trial is currently recruiting PwPs.

A Study to Assess the Safety of GRF621 Infusions in Subjects With Parkinson's Disease and Cognitive Impairment - Full Text View - ClinicalTrials.gov

Youngest plasma !
 

I've come across some PD pre-clinical research with mice, using cord blood plasma (CBP). Possible future plans include combining CBP with mesenchymal stem cells.

Gutting the brain of inflammation: A key role of gut microbiome in human umbilical cord blood plasma therapy in Parkinson's disease model. - PubMed - NCBI

Mid-2020 update regarding "young plasma for PD"
 

Here is my understanding of the current state-of-play regarding "young plasma for PD" clinical trials.
​
​The "young plasma for PD" trial that Nan_Cyclist took part in (NCT02968433), conducted at the Stanford Movement Disorders Clinic, is now overdue for completion.​
Status: Active, not recruiting
Estimated Study Completion Date: December 2019 (no results published AFAIK)
​
​Independently of this, researchers (from Stanford University and Alkahest) who conducted the earlier "young plasma for AD" trial (NCT02256306), have "distilled" young plasma into an injectable "drug" (GRF6021) that is now being tested in a Phase 2 trial involving 90 volunteers with either PD or PD with mild cognitive impairment (NCT03713957).​
Status: Active, not recruiting
Estimated Study Completion Date: November 2020
​
​An earlier version of the drug (GRF6019), consisting of about 400 proteins, was tested on volunteers with either mild-to-moderate (NCT03520998 ) or severe (NCT03765762) Alzheimer's disease.​
Status (of both): Completed
Results: In December 2019, Alkahest presented data from NCT03520998.

Alkahest Presents Data from Phase 2a Study in Mild-to-Moderate Alzheimer’s Disease:
Alkahest Presents Data from Phase 2a Study in Mild-to-Moderate Alzheimer’s Disease - Alkahest

In addition, Alkahest have recently started a trial "Assessing Efficacy and Safety of AKST4290 in Subjects With Parkinson's Disease on Stable Dopaminergic Treatment". AKST4290 (a non-plasma-derived product) is an orally-administered small molecule that acts as a modulator of inflammation. More information on AKST4290 (formerly called ALK4290) is available in this SoPD blog post from Simon (December 2018):
From Alchemy to Alkahest | The Science of Parkinson's

For anyone who might be interested, the new PD trial is currently recruiting PwPs.
Study Assessing Efficacy and Safety of AKST429 in Subjects With Parkinson's Disease on Stable Dopaminergic Treatment - Full Text View - ClinicalTrials.gov

Mid-2020 update update!
 

The "young plasma for PD" trial that Nan Cyclist took part in (NCT02968433), conducted at the Stanford Movement Disorders Clinic, has published its results.

PNT Article - Young Plasma Infusions Safe and Potentially Helpful, Small Trial Finds:
Young Plasma Safe and Potentially Helpful in Parkinson's, Trial Finds.

See also this SoPD blog post from Simon:
The Stanford Parkinson's Disease Plasma Study - The Science of Parkinson's