Has anybody tried nilotinib or heard anything regarding clinical trials for nilotinib and PSP? It was on Fox News in May.

[LyndaEllis]

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I wrote about nilotinib on this site (but it seems one cannot find my past post on this site even if you use the tag). However, I wrote a similar post on the CurePSP site, so if you Google "nilotinib psp" you'll see the link.

Hope it will help.

Cheers

[LyndaEllis]

thanks a lot Strelley

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This was in response to the article:

I often visit the UK PSP Association site and earlier this week the same article was mentioned. My reply was 4 days ago, after a quick look at their use of nilotinib. I tried to keep my reply simple, and I also noted my own reservations (even though I am no expert in this area, and only express my impressions from general reading). Here's what I said to the UK PSP forum when they mentioned the news item they had seen...

The following is my understanding and I don't know if anyone really wants to knows the "ins and outs" of the research. The news item does say "potential" treatment, so we would have to wait and see, hopefully with optimism.

Some think that the death of neurons (and other brain cells) in PSP (and related diseases) can be attributed to the formation of "garbage" (called neurofibrilliary tangles plus other bits) as described in this research news. They have been successful in mice in "removing" (by a process called autophagocytosis -autophagy) this garbage without destroyng the neurons (by using a drug called nilotinib -tyrosine kinase inhibitor - used succesfully to actually kill cancer cells in a certain type of leukaemia).

It sounds like a very useful clinical trial, and they say it can remove the tangles (caused proteins that have "gone wrong" and destabilised the neuron, causing cell death- those proteins are called tau in PSP/CBD and alpha synuclein in Parkinson's, and other proteins for other neurological diseases).

They have to use a small amount (about a thousand time less in mice, and hundred times less in human trials, than for killing human leukaemia cells) because they only want to remove the garbage without damaging the neuron itself.

It sounds exciting, but one must be reserved until it has had full clinical trials. The drug itself has some serious side effects (has a Black Box USA warning).

I have a few reservations (but I'm not an expert in this field), and I don't want to sound negative but I guess I will!!!! The researcher admits that this drug should be used "early" in the disease, and we know that the tangles (garbage) can start 15-25 years before symptoms, so how early is early (when symptoms first appear?)

Then some feel the tau protein that forms into garbage (in PSP/CBD) starts out doing so as defence mechanism (that is, it's good and not bad - most likely to do with mitochodrial dyfunction). Then there is the problem of being successful in mice. If everything that has been successful in mice translated to success in humans we would have many cures by now. These research studies are often very controlled, and quite unlike the many complex mechanisms making up neurological diseases in the human brain. Finally, other current research has shown in autopsy PSP that some areas of the brain had lots of tau garbage, and little neuron death, while others had very little tau garbage and lots of neuron death. Such researchers think there are more factors that cause the PSP status than the conventional thinking of being tau garbage alone.

The above is an over-simplification, and I look forward to the outcomes of this research. If I have made errors in my understanding of the above, please let me know.

All the best.

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Here is also a response from the neurologist from the Neuroscience department of Addenbrookes' Hospital:

Dear Gerko,

Thank you for passing this on. There are several anti-cancer drugs that work well in mice models of degenerative disease, reducing the build up (or getting rid of) the damaged proteins (tau, alpha-synuclein). The problem is that this is a very long way from working in humans. Even if the drugs are not too toxic (which many of them are), they may not work in the human brain, which has some important differences in its chemistry and blood brain barrier etc. However, I have no doubt that it is a very promising line of research, and promotes the search for less toxic equivalents, and versions of these drugs that get into the brain effectively to cure or halt PSP. The current drugs like nilotinib are not the kind of thing one would give lightly, especially to people who are physically frail and at risk of infections like PSP, but they may point the way to safer, easier and effective drugs. .

The articles emphasise that the safety and efficacy are likely to be much better early in the disease – at present we have a problem globally that most patients with PSP take 2-3 years to get the diagnosis. Solving that problem of delayed diagnosis (by education of doctors and the public, and by ‘biomarker’ tests that can early on tell the difference between say PSP and PD) will greatly help the ability to clinical trials to succeed. Getting such biomarkers, and testing them, is part of our work here (which you and C have both helped with already, and a paper will be coming soon) and it is a major aim of the new national PSP research network we have set up, linking seven UK PSP centres with PSPA funds.

Bw

James

[jillannf6]

Hi,i would like to know what research is,being done but,I ,up guess not a lot at the,moment re,PSP

Lol jiłll