Drug delivery allows passage thru Blood Brain Barrier
 

UCL research team breakthrough in delivering drugs to the brain
8 March 2013

http://www.ucl.ac.uk/news/news-artic...rebreakthrough

Researchers at UCL have made a breakthrough in the way that drugs could be delivered to the brain.

Ijeoma F. Uchegbu, Mariarosa Mazza, Andreas G. Schätzlein and their colleagues have tackled the difficult problem of constructing drugs which are able to pass through the blood-brain barrier – a mechanism which prevents many chemicals in the bloodstream from passing into the brain, including synthetic compounds administered as medication as well as harmful environmental toxins.


A new class of drugs – peptide drugs – are now at the forefront of tackling this problem, which, if solved, could revolutionise delivery of pain relief as well as offer hope in treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Enabling such drugs to cross the blood-brain barrier is key to revolutionising the treatment of these conditions...

I am confused. again.
Is this the same as this?
http://neurotalk.psychcentral.com/thread184739-2.html
MS but not PD?
Is UCL same as U. of London?

different study
 

Hi Bob,
I believe these are two separate studies.
UCL is a research arm of the U of London, UCL.
This study, that Olsen is referencing, is about the kind of "piggy-backing" a medication with a substance that can pass the BBB- in this case a peptide.
The previous study was about attempting to maintain the integrity of the BBB
against the onslaught of MS and other neurodegenerative problems which break it down.
At least, that is how I interpreted the two studies.

Well that's the best thing I have heard since the cops let me off with a warning.
If this is really happening, it would be spectacular to get through The Barrier, and we should cheerlead for it; write to them asking for all updates, show our thanks and support.
... if it appears to be real, there should be pressure made to apply the resources needed, to speed it up.
If it is real, it for sure picks up a Nobel Prize

Bbb
 

================================================== ========

My fault I think. I always knew about the two parallel approaches, but never realised that was causing confusion. In some ways, I felt it was contradictory. One group trying to open up the BBB to get drugs in. Another group trying to shut it down to keep toxins out.
However, The group trying to open it up to get drugs in, will limit the open period time. There will not be a lot of toxins going in, since they are likely to be larger molecules than the drugs.
I have written to Dr Egle Solito, and received a very pleasant and s upportive reply. so I have an idea!! How about I write her inviting her to post an appraisal of my paper, and the chances of success by this route.
If she does not want the hassle of joining, she can send it to me to post.
This may take some time so please be patient. However I think this is the best candidate we have had for a very long time, and have spent 35 years in chemical research.

Ron

Please do so Ron

I'm still confused.

What is the relationship between this work and using liposomes to get drugs through the BBB?

The work we're discussing here was published in ACS Nano earlier this year [1]. Mazza et al. present "a peptide brain delivery strategy using peptide drug nanofibers as a concept and show that self-assembling peptide drugs, which give rise to nanofibers, are able to deliver the model peptide dalargin to the brain and elicit a pharmacological response."

To answer my own question, I understand this to be an alternative method to using liposomes to create drug carrying nano particles that cross the BBB.

In my opinion too little effort has been put into translating earlier work into practical drug delivery systems. For instance, it was known 15 years ago that liposomes could be used to get dopamine through the BBB (see a thread started by moondaughter last year [2]). Whatever happened to that?

References

[1] "Nanofiber-Based Delivery of Therapeutic Peptides to the Brain"
Mariarosa Mazza, Rebecca Notman, Jamshed Anwar, Alison Rodger, Matthew Hicks, Gary Parkinson, Dave McCarthy, Tina Daviter, Julian Moger, Natalie Garrett, Tania Mead, Michael Briggs, Andreas G. Schätzlein, and Ijeoma F. Uchegbu
ACS Nano20137 (2), 1016-1026
http://pubs.acs.org/doi/full/10.1021/nn305193d

[2] http://neurotalk.psychcentral.com/sh...ight=liposomes

John

xenoport working on improving intestinal absorption
 

not sure how vigorously they are pursuing this after clinical trial results weren't great.

http://www.xenoport.com/research_dev...technology.htm

http://investor.xenoport.com/release...leaseid=708154

Ronald W. Barrett, Ph.D., chief executive officer of XenoPort, stated, “While we observed an impressive reduction from baseline in ‘off time’ for 279/CD dosed three times per day, we are disappointed that this trial did not provide a clear indication of the benefit, other than dosing frequency, of 279/CD for advanced Parkinson’s disease patients compared to optimized doses of Sinemet. This may have been due to the large reduction from baseline in ‘off time’ observed once patients had their Sinemet dose optimized within the trial. Given that the goal of the trial was to demonstrate a clinical benefit over Sinemet, it was important that both treatments were equivalently optimized using specific guidelines. We intend to further analyze these data, including investigation of possible explanations for the outliers. We also plan to discuss these results with Parkinson’s disease experts and possibly with regulatory authorities to determine next steps, if any. We will defer further investment in this program pending the outcome of our data analysis and these discussions.”

Well, they’ve got traction, what with the recently merged GlaxoSmithKlineMerckSandofBayerFritoLayExxon handling the sales of the deftly-named “Horizont”, a name much mocked by Reverette123 and accomplices on this very site.

XenoPort:
We are a biopharmaceutical company focused on developing and commercializing a portfolio of internally discovered product candidates for the potential treatment of neurological disorders. Our first product, Horizant® (gabapentin enacarbil) Extended-Release Tablets, is currently being promoted by GlaxoSmithKline (GSK) in the United States. Regnite® (gabapentin enacarbil) Extended-Release Tablets is approved for the treatment of moderate-to-severe primary restless legs syndrome in Japan. Astellas Pharma Inc. holds all development and commercialization rights for Regnite in Japan and five Asian countries. XenoPort’s product candidates are being developed for the potential treatment of spasticity, Parkinson’s disease and relapsing-remitting multiple sclerosis.

(Well I’m happy for the Japanese, the only country getting their restless leg syndrome straightened out). Xenoport seems to try hard and may find a breakthrough, but they do sound a bit discouraged about their Parkinson's efforts.

But is not the same study as the one from the University of London – that one is exciting; although right away I worry that if we can get levodopa through the blood brain barrier, basically by subterfuge, smuggling molecules one by one over the border: (or smuggling bicycles) will that also open the pathway to having all sorts of unwanted things getting into our brains (such as, any song by Celine Dion).

What reasons does the brain have to keep out levodopa? Will our brains rejoice or retaliate if we Take Down That Wall. It turned out great to tear down the Berlin Wall; but the Great Wall of China was inadequate to keep out the barbarian hordes. And then there was the Maginot line – you just had to go around it. Can we with impunity traverse the brain border and deliver the drugs straight to the end user? It would be a huge breakthrough. Hope springs eternal....

It would be very interesting to hear from Ron Hutton and the U. of London and JohnT and others about what they are all thinking about this; where it comes from and where it is going.
Remember the New Yorker fretting about Europe surpassing the U.S.A. in brain research? Eh?

I'm one of the authors of that paper (I did some of the multiphoton microscopy imaging for it) so if you have any questions I could help with, let me know!