Prosavin update!
 

Hi everyone,

I found this tiny tidbit buried in a newslink and find it encouraging...here's to hope:

Up at Oxford
Oxford Biomedica, the FTSE-listed biopharmaceutical firm, saw its shares rise nearly 6% to 23.25p after encouraging news in the development of its gene therapy treatment for Parkinson's disease. The aim of its ProSavin treatment is to introduce genes responsible for dopamine production into cells that populate the area of the brain that is dopamine deficient. Analysts at Panmure Gordon noted that a second patient has been "dosed" on ProSavin. "The importance of the second patient being dosed is that it comes a full month after the first patient, which implies that no issues were raised on safety," Panmure said, adding that the company remains "well capitalised". It repeated its buy recommendation on Oxford Biomedica and its 69p price target

Yep I have restrained from ..
 

posting about Prosavin, the investor boards are oozing optimism, reminds me of GDNF !!

Long way to go here.

Neil.

surely not
 

But don't you think, given the GDNF history in the big pharma world, that surely no one would go down that path again? Not to say that if there are issues, like it doesn't work, they will stop the trial(s), but otherwise I sure would like to believe that they would have thought of GDNF before the human trial started. For example, wouldn't a company have already thought of, and addressed, delivery mechanisms (apparently was a big issue in GDNF?), and either else resigned themselves to the product being delivered by brain surgery and therefore on a one-at-a-time basis (and thus, much less profitable than the en masse take-a-pill one sixe fits all approach)? It's wayyyy too early on a saturday morning to try to articulate what I'm trying to say, but I guess the point is, given GDNF, I would hope they would have worked those kinks out before proceeding this far. But then again...

yes, but then again. It's true stocks are going up for Prosavin - my sister just bought some - and while the news is very sanguine on these gene therapies, I think they are very serious (obviously) things with very serious risks. After listening to the researchers speak about another genetic therapy being developed here in New York, which i think has a very similar delivery system to ProSavin - well, it sounds very promising. But the part that freaks me out is the part about "the main question we have is whether or not the virus that is engineered specifically for insertion into the brain will at some point - and who knows when - decide to mutate randomly and uncontrollably." I really don't want to be the person that that happens in...

It appears to have been the delivery system with GDNF, and the deliveries above and below are not going to be ready for years; Thus, GDNF has not gone quietly into the night...p

Posted April 24, 2008

Stem cell experts: Results take time

By Robert Mentzer
Wausau Daily Herald
rmentzer@wdhprint.com


The science of stem cell research holds real promise, but many practical applications remain far off, scientists said this week at a Wausau conference on stem cell ethics.

Clive Svendsen, a professor of anatomy and neurology at the University of Wisconsin-Madison, conducts research on Parkinson's disease and other neurological disorders.

One promising technique, he said, is the use of stem cells that generate a protein known as GDNF, which can limit degeneration of neurons. Svendsen has conducted clinical tests on rats, and has a new academic paper showing that the same techniques work in the brains of primates. This treatment, he said, could be used to dramatically slow the progress of diseases such as Parkinson's, Alzheimer's and Lou Gehrig's or ALS.

"Cure is a very strong word," Svendsen said. "But I think there are very interesting implications for treatment."
Full article

paula

The promise of gene therapy
 

Over the past several years I have tried to gain as much information on gene therapy for Parkinson's as I could. I don't believe that gene therapy is another GDNF. I am a medical scientist and work extensively with the pharmaceutical industry. (My research is not involved with PD, but I know enough about science and clinical trials to be an informed consumer of data on gene therapy.)

There are three companies that are working hard in this area with slightly different approaches: (1) Oxfordshire Bioscience-in the UK; (2) Ceregene and (3) Neurologix in the US. (If there are others that I am not informed about please let me know.)

As far as I can tell Oxfordshire is actually behind the other two companies in their research. Ceregene's CERE 120 has completed Phase I and will complete Phase II and report results this year in Q4. (Enrollment for Phase II is now complete and patients are still being followed from Phase I as well.) Ceregene entered into a development deal with Genzyme last year that is quite substantial. In addition, Michael J Fox Foundation has contributed funds to Ceregene's research. The results from their Phase I trial are outstanding. Some patients are getting close to 3 years post surgery with no adverse events and continued improvement on standard measures at each follow-up point! This is following a single treatment. PET scans are showing cell regrowth. The cell growth is not out of control in any way.

The Neurologix approach is similar to the Ceregene approach. They have had a similar number of Phase I patients and the findings are very much like the Ceregene findings. Their study was unique in that the patients int he Neurologix study got treatment to only one side of their brains. The results were consistent with this test in that improvement generally occurred on the side of the body that would be predicted by the treatment. The Neurologix patients also showed significant improvement with continued improvement for the study participants who are about 2 years post initial treatment.

Neurologix has just initiated its Phase II study. It is also important to note that the FDA gave Neurologix a Fast Track designation to facilitate their research and potentially bring the drug to market as quickly as possible. (My company works closely with the FDA and Fast Track designation is not easy to come by.)

My wife has had Parkinson's for nearly 5 years now and I know that people with PD have been frustrated in their desire for a cure for years. I don't see gene therapy for PD as a cure, however, the impact looks to be greater than anything else that is in the pipeline at present. For people in the studies that I have read the improvements were in the range of 25%-60%+. Again, please remember that people are continuing to get better over time.

With stem cell research set back by at least a decade by an anti-science Bush administration, I believe that it is far more likely that gene therapy will affect the national and international population of people with this terrible disease. My guess is that (as long as there is no terrible unforeseen event for participants in the clinical trials--over the next year or so) we could see a commercially available gene therapy in the next 3 to 5 years.

That would be very exciting for all of us. Let's hope.

Thanks for a really clear summary! I am wonderng if the companies share data with each other to create a more complete picture. They are each studying a separate aspect. That would give me reason to hope.


paula

I
 

share your view as too where we are at in terms of a cure for Parkinson's 1990NYboy. Gene Therapy appears to be the next step along the way too a cure, as we approach the Embryonic and Nano Medicine era. Fiona raised a concern I hadn't thought about (visions of raving mutant organisms rebelling against what they were designated to do and ending up as FDA agents or cloned Hugo Chavez socialists.):D

Neurologix is one I have been following closely since their success with Nathan Klein and others in 2003. And those trials only involved one side of the brain. The fact that their research team had a New Zealand scientist involved at the top level was exciting, and too hear Neurologix had been granted fast track status in March 08 means their is much too look forward to.

When I mentioned GDNF I meant ...
 

that ProSavin was making claims of great efficacy and that there was a lot of optimistic "noise" surrounding the product. I wasn't comparing the two products.

1990nyboy, great summary, ProSavin is behind other gene therapies in terms of clinical trial progress. However its effects are claimed to be obvious within weeks and (as already mentioned), these effects are hoped to be substantial. As a result it appears to be more black and white than the others, it will either crash and burn spectacularly or be very exciting all within a matter of weeks.

On the other hand it may be hideously over hyped in order to gain investment :)

Fingers crossed,
Neil.

p.s. 1990, there is another trial, the old Avigen now genzyme product, AV201. Seems to be struggling to get interest though and may well have been dropped now that Genzyme are working with Ceregene.

Thanks
 

I can't thank you enough for this, what an excellent and informative summary of information I did not have. Even though it is pouring the rain here, and I mean a gulley-washer as they they, this is such good news I don't even care! Makes me want to go run out and wash the car in the rain!

Thanks for sharing.

Yes, thank you very much for contributing such informed reporting on the development of such hopeful therapies.

*laughs ruefully*

I think it must have been the Ceregene people I heard this past December here in NYC raising this issue (random virus mutations) as a major concern. I wonder how many years we would need to have to know this is not a possiblity.....

How long does it take to know if there are adverse events?
 

Fiona's point is well taken. In general, many drugs can have consequences and impacts that are never shown during the clinical trials. If drugs were observed for years after their initiation before approval, no drug would ever be approved.

Because this is the case, the FDA has what is called post-marketing surveillance. That is, post-approval observation of the drug and its adverse events. Since gene therapies for PD at this point appear to have multi year continuing impact, we will have to see what happens over long periods of time to people who have these procedures. The good news is that at least over the first three years none of the problems that occurred in earlier gene therapies in the early 1990s appear to be taking place.

My own guess (informed only by some recent results from stem cell studies) is that the gene therapies will have an active "lifespan" of a decade or so and then the processes that lead to Parkinson's will again take over.

Even were this the case, there are probably few people who would complain about having this kind of procedure every ten years or so.

Again, let's all keep our fingers crossed that the Ceregene report later this year is as good as the data in the past has looked.

A gene therapy success story ...
 

http://news.bbc.co.uk/1/hi/health/7369740.stm

A 17-year-old whose sight was failing has had his vision improved in a pioneering operation carried out by doctors at Moorfields Eye Hospital.

The London researchers used gene therapy to regenerate the dying cells in Stephen Howarth's right eye.

As a result he can now confidently walk alone in darkened rooms and streets for the first time.

Stephen is the third person to have the operation, and the researchers expect even better results in future cases.

Before the procedure, he could hardly see at all at night and in time he would have lost his sight completely.

His condition was due to a faulty gene that meant that the light-detecting cells at the back of his eye were damaged and slowly degenerating further.

The operation involves injecting fluid with missing gene within a modified virus into the eye.

A fine needle (cannula) is passed through the front of the eye and across the vitreous gel.

The cannula is pushed through the retina, light sensitive tissue that lines the back of the eye.

The fluid is injected beneath the retina, causing it to detach from the underlying pigment layer.

Cells in the pigment layer absorb the fluid and the retina returns to its normal position.

The virus infects cells of pigment layer, supplying the gene required for normal sight.

But, in a delicate operation, surgeons at Moorfields injected working copies of the gene into the back of Stephen's eye.

After a few months, doctors detected some improvements.

But Stephen did not notice these changes until he confidently strode through a dimly-lit maze designed to test his vision.

Until then he had kept walking into walls - and it would take him nearly a minute to walk a few feet.

His doctors were shocked at the improvement.

Professor Robin Ali, of the Institute for Ophthalmology, who led the trial, said: "To get this indication after only three patients is hugely exciting.

"I find it difficult to remember being as excited as I am today about our science and what it might achieve."

The operation gave Stephen the confidence to try out his improved night-time vision on the streets near his home in Bolton.

Before he had only been able to see the bright lights of passing cars, street lamps and brightly-lit buildings but, to his amazement, he found he could see beyond the bright lights. For the first time he could see the cracks on the pavement, the edge of the curb and markings on the street.

He recently began walking home late at night from the railway station.

James Bainbridge, the consultant surgeon who carried out the operation, said: "It's hugely rewarding and exciting to see that this new treatment can have this impact on a person's quality of life."

'To not have to worry about losing my sight is great'

Stephen also says that it has really helped his confidence.

He is now able to socialise more late at night with his friends. And, as an aspiring musician, he says he can see the frets on his guitar better - and can move around more on a darkened stage.

There may well be further improvements. But without the operation it was likely that Stephen would have lost his sight altogether.

The prospect made him depressed. Now he says he can get on with his life.

"When I used to think about it, it would get me really down and depressed. But now I don't have to think about it. It's a big burden lifted."

The gene therapy has not improved the vision of the other two patients who have received it so far - but it may well stop their vision from declining further.

Robert Johnson was the first person to undergo the operation, as reported by BBC News in May 2007.

He welcomed the results so far: "For the team, I am thrilled that their hard work has come off.

"For me - I am simply pleased that I left what I entered with - a level of sight that gives me my freedom. What more could I ask for?"

Professor Ali said that the team now hoped to treat children: "The next stage is to increase the dose of the gene which we anticipate will improve the outcome - and it's also to treat younger patients, who have better residual vision and in whom we expect to see a much greater benefit."

Although the genetic condition that is being treated is rare, the researchers believe that their technique could be used to treat a wide variety of sight disorders, possibly even age-related sight loss.

Mr Bainbridge added: "This is only the beginning.

"What we've demonstrated so far is proof of principle that gene therapy can be used to treat a particular gene disorder."

The research, which has been funded by the Department of Health, has been published online in the New England Journal of Medicine.

Health Minister Dawn Primarolo said: "This is absolutely brilliant.

"It's been done here in the UK with the expertise of the NHS and the science and research of the Department of Health all coming together to offer such hope for gene therapy for the correction of sight - but also for gene therapy generally.

Neil.

Neil
 

That story made the front page of our leading newspaper (The NZ Herald) today together with photo of the individual who had the surgery done on his eye. This will be an eye opener (DUH):D for the Gene Therapy crowd and should give some kudos to the Ceregens and Neurologix of this world. Fantastic too see Gene Therapy reaping some good news.