To all those interested in Nilotinib the 2 Nilotinib trials, one at Georgetown University and the other a MJFF sponsored trial involving 25 research centres. On December 17 MJFF held a special webinar (michaeljfox.org/webinar/res... where the Georgetown University trial results were compared to the MJFF sponsored trial results. The purpose of this special webinar was to in essence warn the public that MJFF strongly disagreed with the Georgetown results as described below.
WEBINAR : Results in Context: Nilotinib in Parkinson’s Disease (NILO-PD)
December 17, 2019
The cancer drug nilotinib repurposed for Parkinson's disease has been closely watched by the patient community. The NILO-PD study -- led by Northwestern University and funded by The Michael J. Fox Foundation -- has found no clinically meaningful benefit or biological effect in people with Parkinson's disease. Join us to hear from members of the steering committee on the trial's design and top-line findings and to ask your questions.
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The proponents of the MJFF essentially said there was no strong evidence at all as to the efficacy of the drug and they were cancelling their phase 3 trial which was to be focused on efficacy. They stated that they have met with the Georgetown people and in a polite way they said they agreed to disagree and racked up the difference in results to a difference in interpretation of the data. But the MJFF group will be presenting a detailed paper at a major Parkinson's conference in February at which time they will scientifically compare the two sets of results. All in all it doesn't look like NIlotinib is going to be the miracle cure that we all had hoped for. Because everyone reacts differently and has different symptoms with Parkinson's I suppose it's possible that some small percentage may find it very beneficial but overall it's not very likely to help very much I feel. My survey of people communicating on the HealthUnlocked blog seems to indicate that a number of people at least had some positive results and when they went off the drug their condition worsened again. One person said that after two years consuming the drug he saw absolutely nothing improve. I guess some of this is placebo effect and because one's feeling of well-being is so subjective that it is quite hard to determine improvements very accurately.
Does anyone hear anything from the Georgetown group? What have they said about the MJFF conclusions and are they going to continue the next phase 3 of their trial?
What you think of all this? What conclusions have you drawn?
Regards,
Dogmatic
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Dogmatic377
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I have to listen to what DR Moussa had to say. My research shows Tasigna never had a chance The deck WAS STACKED against Georgetown is JMO. I may be wrong. The whole story needs to come out. Be patient.
"All in all it doesn't look like NIlotinib is going to be the miracle cure that we all had hoped for."
I'm shocked...truly shocked. I think I said something like "never in a million years", "it is nothing but a paycheck baby", etc.,....but perhaps I was too pessimistic.
I wouldn't be surprised if the spin meisters paraded out at the February conference to demand an equally badly designed Phase III (Phase II design was terrible) for the good of all and to keep everyone involved employed for another 5 years. Tack on another 5 for FDA final approval (if ever), and we are talking about 2030 for the branded form to hit the shelves.
A deep in the weeds question, so here goes your deep in the weeds answer.
If you believe the theory behind why they even looked at this drug again, then the obvious answer is yes.
If the theory is totally questionable in real life (human) applications, then I would say no, which is the way I lean.
Specifically, quoting NIH:
Nilotinib (AMN107) and dasatinib (BMS354825) are designed to overcome imatinib resistance in CML (i.e. Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, is a type of cancer that starts in the blood-forming cells of the bone marrow and invades the blood.).
Nilotinib is a selective Bcr-Abl inhibitor, which is more potent (at least 20 fold more) than imatinib against wild-type Bcr-Abl and is also active against 32 of 33 (except for T315I) imatinib-resistant Bcr-Abl mutants.
The critical issue for PD (not CML):
Are Bcr-Abl mutations relevant in the progression of PD? Most significantly inhibition of c-Abl kinase activity by small molecular compounds used in the clinic to treat human leukemia have shown promising neuroprotective effects in cell and animal models of PD.
Did they actually examine in autopsy (human) brains CML patients with PD for c-Abl kinase activity? Obviously NOT. Should they have tried to do so before jumping on the bandwagon? Obviously YES....at least a few.
Once again, a "leap of faith" that really hasn't lead anywhere of significance, but perhaps I am being too objective here because I have no skin the game.
Sharon, in retrospect, I fully agree, more PK research should have been done prior to the start of both of these trials. Too much benefit was given to Georgetown’s open label trial and their “miracle” results. Nothing from these trials can really be used to ascertain whether or not the c-abl hypothesis has validity since there really was no brain penetration of the drug (less than 0.3%). There is some evidence that all four of the other c-abl inhibitors currently being researched have better penetration. Nevertheless, this should be investigated prior to the start of expensive, long term trials.
Other than Georgetown trying to ram through a phase 3, Nilotinib will not be researched for neurological use any further. There is no logical reason to do so.
So much hype on this CML drug initially for PD with little to support it other than the hype, which most bought. Unfortunately, MPTP treated Mice don't have human brains.
Hypothetically, they groups both pursued Nilotinib because it showed from their perspective dramatically improved penetration compared to the other c-Abl inhibitors. However, where they obtained that information is questionable since they never ran a thorough test of any significance before embarking on this "miracle cure" re-purposed CML drug.
Back in 2014, this in vivo study: "The c-Abl inhibitor, Nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson's disease".... raised the issue of the need for head-to-head comparisons of C-Abl inhibitors because they questioned the efficacy of Nilotinib. "we observe no reduction in the tyrosine phosphorylation of parkin and the parkin substrate," Somewhat important I would guess in treating PD progression.
I also guess no one bothered to read this in vivo study results and understand why they recommended what they did.
Several useless drugs have gone to Phase 3 over the years, and one is actually on the drawing board after failing Phase 2, so nothing would surprise me here.
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Nilotinib Does Not Show Promise for Benefit in Phase II Nilotinib for Parkinson’s Disease (NILO-PD) Trial
Long‐Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease (Nov 20, 2020) 
How many know that H2, hydrogen water has positive effects for those with Parkinsons? I didn't know.
Reply from MJFF re High Dose Thiamine
