I am following IKT148009 development closely. I think it is one of the most potentially interesting new drugs in trial . There is rock solid science behind it. The company had a methodology for identifying treatments for the disease that was specific and targetted.
I caution against a knee-jerk reaction to mouse research as discussed in this video. They did not "make PD" with MPTP and then treat the artificial damage created by that poison. They demonstrated that they could make the disease proper from start to finish by triggering a particular pathway.
They also cracked the Beta Amyloid / alpha synuclein mystery - always showing up at the scene of the accident, but not causing it. What results is a coherent, integrated model of PD progression and development, which is internally consistent
The bit I really like is the comment about administration of this molecule in animals with a fair bit of progression, about the equivalent of 10 years progression in humans - what they found was...
not only did it halt the disease progression (as intended), but to their surprise it reversed the damage so far to date. "So while we've called it neurodegeneration, You don't actually lose the neurons. They're dysfunctional , but they're not gone."
It was disappointing the phase 2 trial referred to in this video was halted by the FDA - but that hold is now lifted. It's probably set development back close to a year. But they are not hanging about getting the trial work done, and it is exciting. Well I think so!
It appears from this poster presentation they were using the A53T mouse, which I agree is a good Parkinson's model: d1io3yog0oux5.cloudfront.ne...
Very interesting:
"When the expression of A53T is turned on, but c-Abl is genetically deleted from the mouse brain, there is little if any neurodegeneration. Thus, even though aggregates of alpha- synucleiln are present in the right region of the brain, they don’t cause disease in the absence of c-Abl."
"We have come to believe that while alpha- synuclein aggregate formation is necessary for Parkinson’s disease initiation and progression, it is not sufficient to cause disease on its own. Rather, internalization of aggregates by the affected neurons results in c-Abl activation and all the downstream processes of neuronal dysfunction/degeneration arise from internal processes, at least in early phases of disease. By contrast, c-Abl inhibition not only shuts down processes driving dysfunction/degeneration, c- Abl inhibition also restores clearance processes capable of reducing or clearing pathological alpha-synuclein from the affected neurons."
What is not to like - in the P1b trial treated patients were significantly worse on the UPDRS part III after 7 days, vs. placebo patients were better. Do not know if it was statistically significant but these numbers are certainly clinically significant and not in a good way. Hopefully they do better in the phase 2 trial. But these Phase 1 results make this not something I am inclined to invest in:
Phase 1b trial results, per Inhibikase Therapeutics
A phase 1b trial is primarily (only really) safety , tolerability, and pharmacokinetics. The trial was terminated early because the sponsors, and the FDA agreed there was a strong case to initiate a phase 2 study, which they did with the 201 study
There were 6+2 PD patients in one group, and 6+1 patients in the other. Dosing was for 7 days. Assessments of UPDRS in a pseudo-off state. I think the conclusion drawn by the trial sponser deserves inclusion with your table
PD assessments in the practically-defined offstate in a small number of PD patients demonstrated that IkT-148009 does not worsen disease, but we cannot conclude anything about potential benefit from a short-duration dosing study in a small number of patients. IkT-148009 has begun a Phase 2, 3-month dosing study under NCT05424276.
Yes. With very good reason. I cautioned in my post about mouse phobia.Normally mouse research gives mice, who don't get PD, a similar set of parkinson's symptoms by destroying the neurons with a poison called Mptp. Then they see if their treatment can make the mice better. But while the mice have dead neurons, the same as humans, they don't have the ongoing disease process. So when the drug is then tried on humans it doesn't work because the real parkinson's disease process keeps on happening.
Say you make mice with mptp induced parkinson's better by a stem cell transplant. The transplant will restore normal movements in mice and live till the mouse dies unless some mean lab technician poisons them with mptp again. But in humans the stem cells will start to die like the neurons they were born with did because the ongoing disease process hasn't been stopped
This research is different. They describe a true parkinson's disease "chain". A process of self sustaining reactions which cause the disease which in turn kills the brain neurons, but in addition does all the other non-motor stuff too.
So they start this process, or pathway that they think causes PD in humans, and sure enough it causes PD in mice too. Without mptp.
Then, they block the bad stuff that's part of the pathway and the PD gets better. But if they stop blocking it, the pathway keeps on causing the disease same as in human PD
If they want to see the effect of new variations they can't use monkeys because they are not poisoning them with mptp overnight. They have to start this parkinson's disease chain of events and wait for it to grow into visible PD, That process takes more than 10 years in humans. Roughly, normally, humans mice and monkeys all get PD by this process for about 1/3 of a lifetime. In humans that's 25 years, in monkeys maybe 10 years and in a mouse one year
So if you want to try new stuff using this "real" PD, instead of mptp "fake" PD, it would take 10 years in monkeys but just a year in mice.
Been keeping an eye on this one as well Poo as I remember Dr. Werner who is the Company, in one of the videos sounding very confident that they found something different and that Parkinson's would be the first neuro degenerative disease to fall.
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