9 replies to this topic

[zen]

http://scienceblog.c...-brain-protein/ http://hmg.oxfordjou...e6-d0f133651625

[Logic]

New info:

IT IS the first drug that seems to directly target the causes of Parkinson’s disease. People taking part in a safety trial have had their symptoms reversed, allowing them to talk, get out of bed and feed themselves once again....
“We’ve seen patients at end stages of the disease coming back to life,”...
https://www.newscien...ent=NewTemplate

"The use of nilotinib in doses much smaller than are used to treat cancer, which is up to 800 milligrams daily, was well tolerated with no serious side effects," Pagan explains.
For the trial the doses were kept between 150 and 300 milligrams daily, he added.
http://www.techtimes...stage-trial.htm

Most discussion seems to be here:
http://www.longecity...lopment-theory/

[geo12the]

It's very cruel that there is this promising medication for this terrible disease and they are not making it more widely available but instead are  giving people the same old dompanine replacement therapy.

[niner]

It's very cruel that there is this promising medication for this terrible disease and they are not making it more widely available but instead are  giving people the same old dompanine replacement therapy.

 

Nilotinib is an approved drug, so a doctor could prescribe it "off label", meaning for an indication other than the one it was approved for.  Doctors tend to be very cautious, though.  ("First, Do No Harm.")   Weighing a very small chance of drug-induced harm against the greater harm of inaction is an exercise that some doctors don't seem to be up for. 

[Logic]

A big problem is cost.

 

Cost is:
$ 12.95 per mg.
That works out to:
$ 1942.50 - $ 3885 per month for the tested dosage of between 150 and 300 mg per day.
IF you get it from Novartis... 

I have quotes at around $ 0.05 per mg, depending on batch size, from Chinese manufacturers.
Proper testing cost needs to be added, considering the source.

 

"...induce[s] autophagic protein clearance and modulate brain and peripheral immunity..."
https://neurology.ge....edu/moussa_lab

 

 

Nilotinib-induced autophagic changes increase endogenous parkin level and ubiquitination, leading to amyloid clearance

Alzheimer's disease (AD) is a neurodegenerative disorder associated with amyloid accumulation and autophagic changes. Parkin is an E3 ubiquitin ligase involved in proteasomal and autophagic clearance. We previously demonstrated decreased parkin solubility and interaction with the key autophagy enzyme beclin-1 in AD, but tyrosine kinase inhibition restored parkin-beclin-1 interaction.

 

In the current studies, we determined the mechanisms of nilotinib-induced parkin-beclin-1 interaction, which leads to amyloid clearance. Nilotinib increased endogenous parkin levels and ubiquitination, which may enhance parkin recycling via the proteasome, leading to increased activity and interaction with beclin-1. Parkin solubility was decreased and autophagy was altered in amyloid expressing mice, suggesting that amyloid stress affects parkin stability, leading to failure of protein clearance via the lysosome. Isolation of autophagic vacuoles revealed amyloid and parkin accumulation in autophagic compartments but nilotinib decreased insoluble parkin levels and facilitated amyloid deposition into lysosomes in wild type, but not parkin mice, further underscoring an essential role for endogenous parkin in amyloid clearance.

 

These results suggest that nilotinib boosts the autophagic machinery, leading to increased level of endogenous parkin that undergoes ubiquitination and interacts with beclin-1 to facilitate amyloid clearance. These data suggest that nilotinib-mediated autophagic changes may trigger parkin response via increased protein levels, providing a therapeutic strategy to reduce Aβ and Tau in AD.

http://connection.eb...yloid-clearance

 

IIRC Parkin is also involved in mitophagy..!
 

Edited by Logic, 23 December 2015 - 10:01 AM.

[noot_in_the_sky]

I just started a group buy page:

http://www.longecity...inib-group-buy/

[Logic]

Nilotinib group buy:
http://www.longecity...ndpost&p=765364
 
If you are interested in acquiring Nilotinib prices are as follows:

• Nilotinib $ 8.61 per gram.
• 3rd party testing: $ 600 divided by the number of people that commit to the buy.
• 6 people have committed to the group buy so far, so $600/6 = $ 100 each. I am working on 6 people. ie: add $100 to the above cost.
• Postage from the testing lab has to be added and will differ depending on you location.

So far the following people have committed to the group buy:

• resveratrol_guy                   100 g     $ 961.00  
• ceridwen                              30 g      $ 358.30      
• Logic                                    30 g      $ 358.30     
• noot_in_the_sky                  50 g       $ 530.50
• LongLife                              100 g     $ 961.00
• Der Springende Punkt         20 g       $ 272.20 

Persons who has paid so far:

• resveratrol_guy
• Logic
   

If you are interested please PM me with your address and I will supply my Paypal Email address and the cost of postage from the lab and the lab's details.

• If a minimum of 200 grams is not reached I will refund those who have paid.
• If the number of people is less than 6: More money will have to be paid in for testing.
• If the number of people is more than 6: I will refund the difference.

Timeline:

• Arrival at testing lab after payment of the supplier: 4-6 working days.
• Testing and splitting/packaging for end destination: 5-7 working days.
• Postage to final destination:  unknown.

I am holding thumbs that the buy will be successful, so do contact anyone you think may be interested to bring the cost down as much as possible.

[stefan_001]

With Logic working hard on a group buy perhaps it is good to repeat what the drug does. I am still trying to understand what could e the anti aging benefit to a middle aged person.

 

Nilotinib-induced autophagic changes increase endogenous parkin level and ubiquitination, leading to amyloid clearance

Alzheimer's disease (AD) is a neurodegenerative disorder associated with amyloid accumulation and autophagic changes. Parkin is an E3 ubiquitin ligase involved in proteasomal and autophagic clearance. We previously demonstrated decreased parkin solubility and interaction with the key autophagy enzyme beclin-1 in AD, but tyrosine kinase inhibition restored parkin-beclin-1 interaction.

 

In the current studies, we determined the mechanisms of nilotinib-induced parkin-beclin-1 interaction, which leads to amyloid clearance. Nilotinib increased endogenous parkin levels and ubiquitination, which may enhance parkin recycling via the proteasome, leading to increased activity and interaction with beclin-1. Parkin solubility was decreased and autophagy was altered in amyloid expressing mice, suggesting that amyloid stress affects parkin stability, leading to failure of protein clearance via the lysosome. Isolation of autophagic vacuoles revealed amyloid and parkin accumulation in autophagic compartments but nilotinib decreased insoluble parkin levels and facilitated amyloid deposition into lysosomes in wild type, but not parkin mice, further underscoring an essential role for endogenous parkin in amyloid clearance.

 

These results suggest that nilotinib boosts the autophagic machinery, leading to increased level of endogenous parkin that undergoes ubiquitination and interacts with beclin-1 to facilitate amyloid clearance. These data suggest that nilotinib-mediated autophagic changes may trigger parkin response via increased protein levels, providing a therapeutic strategy to reduce Aβ and Tau in AD.

http://connection.eb...yloid-clearance

 

IIRC Parkin is also involved in mitophagy..!

[Logic]

With Logic working hard on a group buy perhaps it is good to repeat what the drug does. I am still trying to understand what could e the anti aging benefit to a middle aged person.

 

Nilotinib-induced autophagic changes increase endogenous parkin level and ubiquitination, leading to amyloid clearance

Alzheimer's disease (AD) is a neurodegenerative disorder associated with amyloid accumulation and autophagic changes. Parkin is an E3 ubiquitin ligase involved in proteasomal and autophagic clearance. We previously demonstrated decreased parkin solubility and interaction with the key autophagy enzyme beclin-1 in AD, but tyrosine kinase inhibition restored parkin-beclin-1 interaction.

 

In the current studies, we determined the mechanisms of nilotinib-induced parkin-beclin-1 interaction, which leads to amyloid clearance. Nilotinib increased endogenous parkin levels and ubiquitination, which may enhance parkin recycling via the proteasome, leading to increased activity and interaction with beclin-1. Parkin solubility was decreased and autophagy was altered in amyloid expressing mice, suggesting that amyloid stress affects parkin stability, leading to failure of protein clearance via the lysosome. Isolation of autophagic vacuoles revealed amyloid and parkin accumulation in autophagic compartments but nilotinib decreased insoluble parkin levels and facilitated amyloid deposition into lysosomes in wild type, but not parkin mice, further underscoring an essential role for endogenous parkin in amyloid clearance.

 

These results suggest that nilotinib boosts the autophagic machinery, leading to increased level of endogenous parkin that undergoes ubiquitination and interacts with beclin-1 to facilitate amyloid clearance. These data suggest that nilotinib-mediated autophagic changes may trigger parkin response via increased protein levels, providing a therapeutic strategy to reduce Aβ and Tau in AD.

http://connection.eb...yloid-clearance

 

IIRC Parkin is also involved in mitophagy..!

 

 

Thx Stephan_001

Yes Parkin is also involved in mitophagy.  Perhaps I should post in the C60oo subforum!?  

 

PINK1- and Parkin-mediated mitophagy at a glance

Mitophagy is the selective engulfment of mitochondria by autophagosomes and their subsequent catabolism by lysosomes (see Poster). Starvation induces a less-selective form of autophagy in which cytosol and a variety of organelles are engulfed into autophagosomes, which leads to their degradation in order to supply nutrients to compensate for the loss of external supplies. It was initially found that mitochondria are selectively engulfed by autophagosomes following a loss in membrane potential (Lemasters et al., 1998), suggesting that mitophagy mediates selective removal of damaged mitochondria. This idea has been supported by recent knockout mouse models, where loss-of-function of ATG7, which functions in the autophagy pathway, results in an accumulation of defective mitochondria in certain tissues (Komatsu et al., 2005; Wu et al., 2009). Among the first events in quality control by mitophagy is the distinction between damaged mitochondria and healthy mitochondria. Following their identification by PINK1, defective mitochondria are engulfed in double-membraned autophagosomes that fuse with lysosomes, thereby merging their contents and allowing hydrolytic degradation (reviewed by Kim et al., 2007). In addition to quality control, mitophagy occurs to regulate mitochondrial number (Zhang et al., 2009b) and eliminate mitochondria during the development of specialized cells or tissues such as reticulocytes (Kundu et al., 2008; Mortensen et al., 2010; Zhang et al., 2009a). Overexpression of Parkin has been found to induce the complete removal of mitochondria from cells by mitophagy when mitochondria lose their membrane potential (Narendra et al., 2008). As Parkin has also been found to selectively bind only to damaged mitochondria it has been suggested that Parkin might mediate a quality control pathway of mitophagy.

http://jcs.biologist...ntent/125/4/795

 

Personally, I can't help thinking that occasional Nilotinib use may be most benificial as a means of mitochondrial quality control when using mitochondrial protectors like C60oo.
I am currently off of C60oo in anticipation of taking a dose, followed by C60oo again about 8 hours later.

[Logic]

Group Buy Target reached!
 
People who have paid:

• 
  
• resveratrol_guy 100g
• LongLife 100g
• Der Springende Punkt 20g
• noot_in_the_sky 58g
• Logic 30g
• rikelme 10g
• ceridwen 77g
• Alex_G 30 g
• 'other buyer' 200g (wants to remain anonymous)

Total: 625 grams
That means that we have reached our target.  Thx everyone!  
I will be ordering the Nilotinib on Mon, Mar 21 at 0H00 GMT.
(That's at 8pm Sunday night in New York)
Any funds received after this time will have to wait for the next Nilotinib group buy.