156 replies to this topic

[deetown]

I have to assume they had a reason for administering this orally vs Injection.  Since it's likely only a small portion is getting into the blood stream the cost to administer orally would be very high.  I wish they would go explain why they chose oral.  

 

I want to take this orally if the cost can be made to work.  I personally would be willing to pay $.5/mg at a daily cost of $60 maybe more to try it for a couple months.  I'm getting the feeling from people I talk to that the price point may not be achievable.  In which case I guess I'd be forced to experiment with injection.  

[Mian Ali Ismail]

Treatment with DNase I in the present case allowed our patient to withdraw from a terminal state and resulted in significant improvements in cognitive and behavioral function, including the ability to walk and perform everyday tasks with near independence. DNase I was used as a repurposed FDA-approved medication [14]. Significant recovery was observed in all areas of cognitive and motor function, indicating the possibility of a DNase-sensitive target involved in generating the symptoms of AD.

Cell-free DNA, including bacteria-derived DNA, may be one such target [15]. Circulating cf-DNA has been observed to play an important role in the progression and maintenance of different disease states, including cancer, stroke, and other [16, 17]. Our previous research revealed its possible role as a therapeutic target in graft-versus-host diseases [18].

Though there are various suggestions regarding the origins of serum and plasma cf-DNA, many researchers have speculated that it results from apoptosis, necrosis, or both, or that this cf-DNA is secreted by cancer cells, microorganisms, hematopoietic cells, and/or neutrophils [19]. However, the physiological role of cf-DNA in the progression of these diseases remains to be discovered. Some have theorized that this role is mechanical in nature, increasing blood viscosity and leading to ischemia, while others suggest that cellular uptake of cf-DNA is involved in the development of metastatic conditions [20]. Little research has focused on the role of cf-DNA in neurodegenerative conditions, particularly AD. Further studies are required in order to evaluate the role of cf-DNA in the incidence and progression of neurodegenerative pathologies.

[Logic]

I have to assume they had a reason for administering this orally vs Injection.  Since it's likely only a small portion is getting into the blood stream the cost to administer orally would be very high.  I wish they would go explain why they chose oral.  

 

I want to take this orally if the cost can be made to work.  I personally would be willing to pay $.5/mg at a daily cost of $60 maybe more to try it for a couple months.  I'm getting the feeling from people I talk to that the price point may not be achievable.  In which case I guess I'd be forced to experiment with injection.  

 

http://www.longecity...ndpost&p=778756

 

So let's do a quick google of dnase gut :

https://www.google.c...chrome&ie=UTF-8

Things start to look interesting at the 2nd link already...
So answering your own question shouldn't be a problem...?

[Mian Ali Ismail]

HI Logic,

 

Any luck with suppliers ?

 

 

[45rpm]

Here's some more information about DNase 1 in the gut...

 

http://www.ncbi.nlm....pubmed/12005024

 

From some of my related research in which I discovered a successful treatment for acid reflux (sorry, but I don't have any links for this info), anti-histamines and histamine blockers would theoretically decrease the levels of DNase 1 in the body. Conversely, L-Histidine, Histamine and Pregnenolone would theoretically increase levels of DNase 1.

 

Also, I found this interesting tidbit...

 

"Among other things, L-histidine is also necessary for the formation of the myelin sheath, which surrounds all nerve cells and protects them from damage, and can be used to prevent certain degenerative conditions, such as Alzheimer’s and Parkinson’s."

 

http://aminoacidstud...rg/l-histidine/

 

Edited by 45rpm, 24 June 2016 - 10:20 PM.

[Mian Ali Ismail]

Email from the tesearch where the trial was done.

 

There is an increasing number of articles showing previously undistinguished role of cell free DNA in a variety of pathologies, as well as an infectious role in their progression

http://www.nytimes.c...-infection.html

[LongLife]

I have to assume they had a reason for administering this orally vs Injection.  Since it's likely only a small portion is getting into the blood stream the cost to administer orally would be very high.  I wish they would go explain why they chose oral.  

 

I want to take this orally if the cost can be made to work.  I personally would be willing to pay $.5/mg at a daily cost of $60 maybe more to try it for a couple months.  I'm getting the feeling from people I talk to that the price point may not be achievable.  In which case I guess I'd be forced to experiment with injection.  

Here are some comparative commercial pricing. We are still looking for bulk; coming soon to a Group Buy near you.

 

Pulmozyme 1mg/ml  (commercial Dnase 1)

 

    Unit                description                                               Cost           Unit

Lufyllin-GG     200-200 mg tablet                                    3.99USD      tablet

Lufyllin-gg           tablet                                                    3.84USD      tablet

Pulmozyme   1mg/ml ampul                                          37.05USD      ml

Pulmozyme   1mg/ml Solution 2.5ml Plastic Container 77.06USD      plastic

Category: Cystic fibrosis therapy adjunct

 

Can those interested in a Group Buy please Personal Message LOGIC, myself or post here. Thanks.

Edited by LongLife, 26 June 2016 - 04:18 AM.

[Der Springende Punkt]

Can those interested in a Group Buy please Personal Message LOGIC, myself or post here. Thanks.

 

 

Still highly interested.
 

[psychejunkie]

I am also interested in group buy, if reasonable price tho!

[Alex_G]

I am interested in a Group Buy. 

LongLife, 

    Unit                description                                               Cost           Unit

Lufyllin-GG     200-200 mg tablet                                    3.99USD      tablet

Lufyllin-gg           tablet                                                    3.84USD      tablet

Pulmozyme   1mg/ml ampul                                          37.05USD      ml

Pulmozyme   1mg/ml Solution 2.5ml Plastic Container 77.06USD      plastic

 

am I reading this chart right in that Lufyllin-GG is a 200mg tablet for $3.99 each?  how much DNase I is in each tablet? that price is pretty good.

[Mian Ali Ismail]

I dont think lufyllin GG will be helpful.

[LongLife]

 

I am interested in a Group Buy. 

LongLife, 

    Unit                description                                               Cost           Unit

Lufyllin-GG     200-200 mg tablet                                    3.99USD      tablet

Lufyllin-gg           tablet                                                    3.84USD      tablet

Pulmozyme   1mg/ml ampul                                          37.05USD      ml

Pulmozyme   1mg/ml Solution 2.5ml Plastic Container 77.06USD      plastic

 

am I reading this chart right in that Lufyllin-GG is a 200mg tablet for $3.99 each?  how much DNase I is in each tablet? that price is pretty good.

 

ALEX_G:

Greetings. As stated, this is a comparative pricing. I got this from the GOOGLE search under "pricing DNASE I". How recent this data is I do not know. Availability? You may need to see friendly doctor and try to convince of a serious dementia state like Parkinson...I imagine.

 

The thought was, and point is, this is some real world pricing via GOOGLE search engine, so please do not read anything more into the data. Thanks.

 

PROBLEMS:

The Dnase I is available in liquid and powder forms. Apparently, both require to be kept below 8C (46F) and can not be frozen but one time.

 

Shipping logistics - cold paks

 

US Customs - wild card. I imagine that there MAY be a RAPID CLEARANCE protocol for temperature sensitive items through US Customs. Don't know yet. 

[Alex_G]

What's interesting is that if Lufyllin-GG was suitable for our purposes and if the price is $3.99 per pill, and it is 200mg of DNase I. That's a pretty good price, maybe a trip to Mexico to pick some up would be worth it.  Anyway, if that is anywhere near the real price that is totally doable at that price. The Pulmozyme is completely off the charts expensive.

Now when I look up Lufyllin it says that it is dyphylline. that doesn't sound like DNase I to me.....

[Mian Ali Ismail]

Yes Alex Lufyllin is a different drug.We might get a quotation soon on Dnase1.We are looking for a reliable supplier and then have to get it tested from a third party Lab.

 

[centralFloridaMan]

does this have any for parkinsons?

sorry for the bad post - what i meant was does this have any implications for parkinson's?

[psychejunkie]

does this have any for parkinsons?

sorry for the bad post - what i meant was does this have any implications for parkinson's?

 

As DNase1 clears floating cell-free RNAs/DNAs, I think it'd help with any neurodegenerative disease!  

[davis89x]

Interested in group buy.

[Jochen]

would also be interested in a group by of this. Checking out everything that could help my dad (lew bodies)

[centralFloridaMan]

am interested in group buy

[centralFloridaMan]

am interested in group buy

[centralFloridaMan]

am interested in group buy

[Mian Ali Ismail]

Regarding the recent developments Longlife is emailing suppliers for Dnase 1.Lets see how it goes.

[Logic]

I am afraid that I have, as yet,  only received the one response I posted earlier.

I suspect this is due to prospective manufacturers being unaware of the potential dramatic increase in demand that would occur should  Pulmozyme have the same effect in all ALZ related cases, so have prepared the following Email to send:

 

...The reason for all the interest in Pulmozyme is this one case study:

http://www.prnewswir...-300280725.html

Due to positive results and the lack of any negative side effects found by the growing group of researchers digging up research on Pulmozyme; interest and demand for it is growing fast and the group impatient!
As you can imagine; should these results be duplicated by the interested group; the demand for Pulmozyme will skyrocket and any company in a position to supply it at a reasonable and competitive price is likely to make a fortune..!!!
ie:  The market grows to the size of the global population with ALZ and related dementias...  That's 44 000 000 people!
http://www.alzheimer...ers-statistics/
This could mean that the numerous companies currently ignoring my Emails wont be doing for much longer..! 

 

One concern is the legal status of Pulmozyme:  It received  orphan drug status in 1993.  Orphan drug protection generally lasts 7 years, so there should be no legal issues, but I cannot find any information explicitly stating that Pulmozyme is not protected anymore.  This probably points to its no longer protected..?

I hope you have some positive feedback on producing Pulmozyme that I can share with the group?

 

Best

 

[Logic]

http://www.longecity.org/

 

My hope is that this will convince prospective suppliers to consider making a small/ish amount that they are able to sell/recoup costs on for us.
The list of companies being Emailed is also growing and has now reached around 30...

ie:  The lack of progress is not due to a lack of effort; its due to everyone I have contacted 'wiping their arses' on my inquiry due to their belief, I believe, that the market is too tiny to warrant a reply.
Well; that and plain bloody bad manners!  

 

If anyone has any ideas on improving the motivational ability of the above Email; plz post.  I am not an advertising pro.
 

[resveratrol_guy]

Logic, thanks for working on this. Have you contacted Sino Biological? They make DNase I as shown here. It seems way too expensive but that might change if they saw higher demand.

 

I think we should stick as close to the case report as possible, and only opt for an analog if the cost proves prohibitive. We just don't know enough about the mechanism of action yet.

 

I'm still dumbfounded as to how DNase I could cleave stuff that's not made of DNA, such as amyloid cages or other plaque forms. It's possible that it does not actually do this at all, but rather, indirectly stimulates the microglia to do so. Either way, it doesn't make much sense to me. What I suspect, pending further data, is that this particular patient was suffering more from the accumulation of cfDNA, than conventional AD plaque. Perhaps he had had a rampant brain infection in the past which left a dangerous amount of the stuff scattered throughout his brain. So in other words, this strategy wouldn't be helpful to most dementia patients.

 

The other way to look at this is to theorize that AD plaques are indicators of dementia moreso than causes -- that in fact they're merely indicators of cfDNA left from previous infections, which is the real culprit. So if we disaggregate the latter, then we'll achieve disease regression. The fact that antiamyloid interventions, although quite successful, have almost universally failed to result in cognitive improvement in established disease cases, would be consistent with this theory. Nevertheless, I'm still very skeptical of all this. I guess there's one way to find out...

 

[Logic]

I have to assume they had a reason for administering this orally vs Injection.  Since it's likely only a small portion is getting into the blood stream the cost to administer orally would be very high.  I wish they would go explain why they chose oral.  

 

I want to take this orally if the cost can be made to work.  I personally would be willing to pay $.5/mg at a daily cost of $60 maybe more to try it for a couple months.  I'm getting the feeling from people I talk to that the price point may not be achievable.  In which case I guess I'd be forced to experiment with injection.  

 

Deetown I believe you are missing a very important point:  

In healthy people Dnase is normally produced in the gut.

Therefore, oral dosing, assuming it gets through the stomach/ Hydrochloric Acid ok, puts it exactly where you want it..!

 

I feel that a very good line of research would be to try and figure out why the gut stops making Dnase and how to fix it.

For all we know its as simple as some probiotic or other!?

[Mian Ali Ismail]

Hi Guies,

 

I recieved an Email from the researchers in which they replied to my question regarding Side effects that there were No Side effects in the patient taking Dnase 1.

 

Best Regards

[Logic]

Logic, thanks for working on this. Have you contacted Sino Biological? They make DNase I as shown here. It seems way too expensive but that might change if they saw higher demand.

 

I think we should stick as close to the case report as possible, and only opt for an analog if the cost proves prohibitive. We just don't know enough about the mechanism of action yet.

 

I'm still dumbfounded as to how DNase I could cleave stuff that's not made of DNA, such as amyloid cages or other plaque forms. It's possible that it does not actually do this at all, but rather, indirectly stimulates the microglia to do so. Either way, it doesn't make much sense to me. What I suspect, pending further data, is that this particular patient was suffering more from the accumulation of cfDNA, than conventional AD plaque. Perhaps he had had a rampant brain infection in the past which left a dangerous amount of the stuff scattered throughout his brain. So in other words, this strategy wouldn't be helpful to most dementia patients.

 

The other way to look at this is to theorize that AD plaques are indicators of dementia moreso than causes -- that in fact they're merely indicators of cfDNA left from previous infections, which is the real culprit. So if we disaggregate the latter, then we'll achieve disease regression. The fact that antiamyloid interventions, although quite successful, have almost universally failed to result in cognitive improvement in established disease cases, would be consistent with this theory. Nevertheless, I'm still very skeptical of all this. I guess there's one way to find out...

 

I will re-Email them with a modified version of the above Email and see if we cant get a deep discount for our experiment RG.  

I doubt they are aware of the fact that the demand for Dnase may be about to skyrocket.

 

 

Psilociraptor1 has shed some light on how Dnase may work:

 

This is interesting though I'm having some internal conflict about it. Dr Judith Milkossy and Alan McDonald have also posted numerous studies identifying spirochetal infections in alzheimers lesions. My issue is that amyloids are also fundamental components of bacterial biofilms and therefor would be expected to bind to microorganisms without necessarily conferring immunity to the host. Unfortunately I do not have access to that full article, but I'm wondering if the authors are conflating "microbial entrapment" with intentional biofilm formation. There is also the possibility that certain bacteria exploit innate immune function and cross seed with endogenous amyloids making the distinction somewhat ambiguous. My personal feelings are that the presence of accumulated amyloids is more suggestive of biofilm formation than functional immune response. Interestingly I've noticed that many herbs that are reported to reverse beta-amyloid deposits are also potent biofilm erradicators. Ie flavonoids and related compounds such as baicelain and EGCG.

Interestingly the use of DNaseI is also a noted biofilm disrupter. I'm surprised to hear of in vivo efficacy though. Especially for a brain disorder.

 

Pretty much exactly what it sounds like. Something that disrupts biofilm development and or the structural integrity of mature biofilms. There is no "one" mechanism for it. DNases have been said to destabalize [biofilms] by cleaving some of DNA that's wound into the biofilm matrix. I don't know enough to say what their exact structural role is. Chelating agents can disrupt some biofilms that rely on iron for structure. Biofilm disruptors may also be proteolytic enzymes, quorum sensor inhibitors, agents which stimulate bacterial disaggregation pathways etc. This is a pretty understudied science and what works in vivo is almost completely unknown but these are the sorts of things studied in labs at the moment.

http://www.longecity...ndpost&p=780542

 

I haven't looked for any supporting studies of these statements..?

 

I think Biofilm disruptors and bacteria killers might synergise with Dnase..?

Some interesting anti pathogens:
http://www.longecity...ndpost&p=780706

[deetown]

This is Team TLR's response:

Please note we can afford the DNase1 material with strongest quality in the amount requested of 45 Mega kiu total material for $11,960.

 

Lead time is approximately 4-7 days.

this would be 20 grams at 1500ku. 

 

I'm sure the price is much higher than other options.  They have agreed to put it in escrow contingent on lab test results.  Finding the lap to conduct the tests has been the difficult.  I have very little background in this field and consider it a hobby.  I know much less about most of this stuff than nearly everyone on these boards.  With that said if someone could help me find someone to properly test this I would appreciate it.   Also if other people are interested at this price I'm happy to include them.  

[Mian Ali Ismail]

Any news on Dnase 1 suppliers guies ?

[gamesguru]

Very interesting theory on biofilms, Logic. And the tidbit about the gut being the natural place and injections being inferior was also refreshing.