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-   -   Phase 2 Trial Shows Nilotinib Potential to Modulate Dopamine in Parkinson’s (https://www.neurotalk.org/parkinson-s-disease/252161-phase-2-trial-nilotinib-potential-modulate-dopamine-parkinson.html)

eds195 08-24-2018 06:21 PM

Phase 2 Trial Shows Nilotinib Potential to Modulate Dopamine in Parkinson’s
 
Phase 2 Trial Shows Nilotinib Potential to Modulate Dopamine in Parkinson’s

Phase 2 Trial Shows Nilotinib Potential to Modulate Dopamine in Parkinson’s

johnt 08-25-2018 02:57 AM

I can only find the Abstract describing this research:
https://www.iaprd-world-congress.com..._Abstracts.pdf

The conclusions:

"a single time oral administration of Nilotinib may increase brain dopamine levels and metabolism. These results suggest Nilotinib, in a dose dependent manner, may have a symptomatic effect through modulation of brain dopamine levels. Additionally, the significant reduction of oligomeric alpha-synuclein, which is expected to increase in the CSF of PD patients as the disease progresses, suggests that Nilotinib may reduce misfolded alpha-synuclein accumulation and have a longterm disease modifying effect. Importantly, the dose response of oligomeric alpha-synuclein and HVA changes to nilotinib suggests that the dose administered may depend on the stage of disease to potentially halt PD progression."

John

RooJr 08-25-2018 04:06 AM

Quote:

Originally Posted by johnt (Post 1266866)
I can only find the Abstract describing this research:
https://www.iaprd-world-congress.com..._Abstracts.pdf

The conclusions:

"a single time oral administration of Nilotinib may increase brain dopamine levels and metabolism. These results suggest Nilotinib, in a dose dependent manner, may have a symptomatic effect through modulation of brain dopamine levels. Additionally, the significant reduction of oligomeric alpha-synuclein, which is expected to increase in the CSF of PD patients as the disease progresses, suggests that Nilotinib may reduce misfolded alpha-synuclein accumulation and have a longterm disease modifying effect. Importantly, the dose response of oligomeric alpha-synuclein and HVA changes to nilotinib suggests that the dose administered may depend on the stage of disease to potentially halt PD progression."

John

Great Find!

jeffreyn 08-25-2018 06:49 AM

Too soon
 
I think an "abstract" is all we are likely to get for quite a while yet. As it says in the PNT article, the Georgetown Phase 2 trial is still ongoing.

zanpar321 08-25-2018 08:49 PM

Quote:

Originally Posted by jeffreyn (Post 1266868)
I think an "abstract" is all we are likely to get for quite a while yet. As it says in the PNT article, the Georgetown Phase 2 trial is still ongoing.

If the present trials show continued safety and success will this drug get fast track status as a breakthrough therapy? Indications so far sure suggest that it qualifies!

https://www.fda.gov/forpatients/appr...st/default.htm

jeffreyn 08-26-2018 02:15 AM

From the conclusion:
"Importantly, the dose response of oligomeric alpha-synuclein and HVA changes to nilotinib suggests that the dose administered may depend on the stage of disease to potentially halt PD progression."

I had a lot of trouble understanding this sentence, and I found the PNT article to be of no help in that regard.

Assuming I've understood it correctly, here is an alternative wording that might (or might not!) be clearer:
"The dose-dependent decrease in oligomeric alpha-synuclein levels (and increase in HVA/DOPAC levels) suggests that (to potentially halt PD progression) the stage-of-disease may dictate the appropriate dose of nilotinib to administer."

Anyway, it seems to me that there is still a lot of research to be done to establish the correct dose for each stage of the disease. This might well affect the prospects for a fast-track approval.

Hopefully, another write-up will appear (from AlzForum, SoPD blog, ...) and shed some more light.

zanpar321 08-27-2018 04:31 PM

Quote:

Originally Posted by jeffreyn (Post 1266895)
From the conclusion:
"Importantly, the dose response of oligomeric alpha-synuclein and HVA changes to nilotinib suggests that the dose administered may depend on the stage of disease to potentially halt PD progression."

I had a lot of trouble understanding this sentence, and I found the PNT article to be of no help in that regard.

Assuming I've understood it correctly, here is an alternative wording that might (or might not!) be clearer:
"The dose-dependent decrease in oligomeric alpha-synuclein levels (and increase in HVA/DOPAC levels) suggests that (to potentially halt PD progression) the stage-of-disease may dictate the appropriate dose of nilotinib to administer."

Anyway, it seems to me that there is still a lot of research to be done to establish the correct dose for each stage of the disease. This might well affect the prospects for a fast-track approval.

Hopefully, another write-up will appear (from AlzForum, SoPD blog, ...) and shed some more light.

Is Radotinib ABL to beat Nilotinib? | The Science of Parkinson's

June 17, 2018 - The competition to stop/reverse Parkinson's is intense!

Our efforts to slow/halt the progression of Parkinson’s are attempting to attack the condition on many different fronts, and (as in the case of the cAbl-inhibitors and GLP-1 agonists – see previous post) we now have multiple weapons potentially available on some of those battle lines.

Ironically in another recent post I commented about the crazy pace of the research at the moment (Click here for that post), and this post is a perfect example of that manic speed. Just days after publishing fascinating results dealing with a novel GLP-1 agonist in models of Parkinson’s, that same research group – led by Prof Han Seok Ko of Johns Hopkins University Medical school – published the research report that was reviewed in this post dealing with a completely different type of drug that exhibits interesting properties in models of Parkinson’s.

A lot of excitement is associated with the efforts to re-purpose the cancer drug Nilotinib for Parkinson’s, and today’s post reinforces the idea that other pharmaceutical companies are also focusing on shifting similar ABL inhibitor drugs to neurodegenerative conditions.

It will be interesting to see how quickly Ilyang Pharmaceutical initiates clinical testing of Radotinib for Parkinson’s.

Tupelo3 09-16-2018 07:15 PM

Quote:

Originally Posted by johnt (Post 1266866)
I can only find the Abstract describing this research:
https://www.iaprd-world-congress.com..._Abstracts.pdf

The conclusions:

"a single time oral administration of Nilotinib may increase brain dopamine levels and metabolism. These results suggest Nilotinib, in a dose dependent manner, may have a symptomatic effect through modulation of brain dopamine levels. Additionally, the significant reduction of oligomeric alpha-synuclein, which is expected to increase in the CSF of PD patients as the disease progresses, suggests that Nilotinib may reduce misfolded alpha-synuclein accumulation and have a longterm disease modifying effect. Importantly, the dose response of oligomeric alpha-synuclein and HVA changes to nilotinib suggests that the dose administered may depend on the stage of disease to potentially halt PD progression."

John


Yes, as Jeff replied, this was only presented as an Abstract at the Oral Poster Presentation of the 2018 iaprd. This is a common occurrence to present abstracts and posters of ongoing clinical resesrch to provide updates as data is analysed.

Tupelo3 09-16-2018 07:46 PM

Quote:

Originally Posted by zanpar321 (Post 1266890)
If the present trials show continued safety and success will this drug get fast track status as a breakthrough therapy? Indications so far sure suggest that it qualifies!

Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review

Although maybe it’s technically possible it would be highly unlikely for this to happen. Fast track is used for new molecules that are ground breaking and greatly needed for a particular disease. There is no need for that in this case as this is already an approved drug. It’s available for any doctor to legally prescribe, if they believe it would be an effective treatment. If data comes out to compel the fda, which hasn’t happened yet, it would just make it easier for doctors to prescribe. So, I don’t think the fda would feel compelling pressure to fast track.

Tupelo3 09-16-2018 08:08 PM

Quote:

Originally Posted by zanpar321 (Post 1266954)
Is Radotinib ABL to beat Nilotinib? | The Science of Parkinson's

June 17, 2018 - The competition to stop/reverse Parkinson's is intense!

Our efforts to slow/halt the progression of Parkinson’s are attempting to attack the condition on many different fronts, and (as in the case of the cAbl-inhibitors and GLP-1 agonists – see previous post) we now have multiple weapons potentially available on some of those battle lines.

Ironically in another recent post I commented about the crazy pace of the research at the moment (Click here for that post), and this post is a perfect example of that manic speed. Just days after publishing fascinating results dealing with a novel GLP-1 agonist in models of Parkinson’s, that same research group – led by Prof Han Seok Ko of Johns Hopkins University Medical school – published the research report that was reviewed in this post dealing with a completely different type of drug that exhibits interesting properties in models of Parkinson’s.

A lot of excitement is associated with the efforts to re-purpose the cancer drug Nilotinib for Parkinson’s, and today’s post reinforces the idea that other pharmaceutical companies are also focusing on shifting similar ABL inhibitor drugs to neurodegenerative conditions.

It will be interesting to see how quickly Ilyang Pharmaceutical initiates clinical testing of Radotinib for Parkinson’s.

Yes, there are better versions of both c-abl inhibitors and glp-1 agonists in development. There are three ongoing trials for approved glp-1 agonists with several newer ones still in clinical research for approval. We willing be reviewing funding applications next week at the LinkedIn Clinical Trials annual meeting for a newly approved c-abl inhibitor and glp-1 agonist to possibly begin neurological research.


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