'A cure for Parkinsons Disease'

Here is a link to that presentation. They start talking about the PD product after 20minutes of other stuff:

http://mediaserve.buchanan.uk.com/Webcasts/oxford050906/lrframes.htm

Trials look like starting pretty soon?


Prosavin preclinical data


RNS Number:9259L
Oxford Biomedica PLC
13 November 2006




For Immediate Release 13 NOVEMBER 2006

OXFORD BIOMEDICA PRESENTS ENCOURAGING PRECLINICAL EFFICACY
DATA WITH PROSAVIN(R) IN PARKINSON'S DISEASE


- Presentation at the 14th Annual Congress of the European Society of Gene
Therapy, 9-12 November 2006, in Athens, Greece -

Oxford, UK - 13 November 2006: Oxford BioMedica (LSE: OXB), a leading gene
therapy company, announced today that new preclinical efficacy results with its
gene-based product for Parkinson's disease, ProSavin, were presented at the 14th
Annual Congress of the European Society of Gene Therapy (ESGT) in Athens,
Greece, which was held on 9-12 November 2006 (http://www.esgt.org). The data
showed, for the first time, that ProSavin outperformed the standard treatment
for Parkinson's disease, L-DOPA, in terms of efficacy without inducing any of
the disabling dyskinesias (movement disorders) that occur following prolonged
treatment with L-DOPA. Also, long-term data showed that ProSavin's therapeutic
benefit was maintained for at least 15 months, the most recent time point,
without any loss of effect.


ProSavin is administered locally to the region of the brain called the striatum,
delivering the genes for three enzymes that are required for the synthesis of
dopamine. These genes are able to reprogram the cells that they enter, enabling
these cells to manufacture and secrete dopamine. The treated brain region
becomes a new endogenous source of dopamine, replacing the patient's own lost
source of the neurotransmitter. Sustained expression of the genes is a key
requirement for the product to be clinically successful.


Dr Palfi, Head of Neurosurgery at Henri Mondor Hospital, Creteil is the
principal researcher conducting the preclinical in vivo evaluation of ProSavin.
At the ESGT meeting, Dr Palfi presented a comparison of ProSavin with L-DOPA in
an industry standard model of Parkinson's disease. In the early stages of
treatment, ProSavin gave high levels of efficacy when evaluated by a series of
clinically relevant parameters. In addition, the benefit of a single
administration of ProSavin was maintained after a prolonged period, whereas the
benefit of continuous L-DOPA therapy waned significantly. Dr. Palfi reported
that ProSavin has been effective to the most recent time point of 15 months.


The higher efficacy of ProSavin combined with the absence of side effects
suggest that ProSavin could be used to replace current standard therapy with
L-DOPA in late-stage Parkinson's disease. These new data add to the extensive
preclinical data package that supports advancement of the product into human
trials.


Oxford BioMedica is planning to start a European Phase I/II trial of ProSavin in
2007 in patients with late-stage Parkinson's disease and has proposed a clinical
plan to progress to a Phase III trial following success in the Phase I/II trial.
The Phase III trial, which is designed to support product registration, could
commence in 2009. Discussions with relevant regulatory agencies are ongoing.


Commenting on the ProSavin data, Oxford BioMedica's CEO, Professor Alan Kingsman
, said: "These new results substantially strengthen the already impressive
preclinical data set for ProSavin and confirm its potential as a treatment for
Parkinson's disease, particularly when other therapies fail. Its duration of
action and lack of side effects are particularly promising. We are now working
towards the start of human trials and have been encouraged by discussions with
the regulatory agencies."

CHECK WITH YOUR NEUROLOGIST BEFORE MAKING ANY CHANGES IN YOUR MEDICATION...LET THE DOCTOR READ THIS AND HELP YOU DECIDE IF THIS THEORY MAY HELP YOU...BY SLIGHTLY CHANGING THE WAY YOU DOSE YOUR SINAMET YOU MAY BE ABLE TO REDUCE SIDE EFFECTS AND TO EXTEND THE NUMBER OF YEARS IT WORKS....

STILL INTERESTED? READ ON!...(and no I am not selling anything!)

 

I am a secondary caregiver as my Father is going on his 12th year with Parkinsons.

 

The first 5 were bearable and my Mom managed ok. Dad got by without taking Sinamt, though he had a lot of side effects from Mirapex and Artane.

I was busy teaching Science and although I lived close, found it tough to find the time to help out....though I'd often come over on the weekends.

 

Years 5-10 became tougher as you know...Sinamet was introduced in year 7 and really helped for a while...but in year 11 Dad got Aspiration Pneumonia...spent a week in the hospital and was severly weakened. With slow rehab and excellent Physical Therapy, Dad improved to about 70%-80% of his pre-pneumonia condition. At 80 years old most Doctors wrote him off. He needed more care but did ok for 2 more years than the hospital doctors gave him. Here we are 2 years later though, and he has swallowing problems during his off periods. He has also developed dykinesias which no Neurolgist seemed able to help with. Then I came upon this theory in my countless internet searches:

 

The Pulsatile Theory of Levadopa Administration:

What does this mean? It means the Levadopa (L-Dopa or "Sinamet") you take is in Big Chunks compared to the natural flow of a non Parkinsons person.

IT IS BELIEVED THAT IT IS THE TAKING OF SINAMET (L-Dopa)IN THIS FASHION THAT PRODUCES MANY OF THE WORST  SIDE EFFECTS OF SINAMET...INCLUDING DYSKINESIAS, EXTENDED OFF PERIODS AND DRUG FAILURE.

 

I did this with my Dad and it really helped! Read on...

 

What does it mean? It means that when you take a tablet or 2 of Sinamet...the sudden rise of LDopa or falling off is stressful, and over time produces Dyskinesias...

 

So if for example you take a 2 tablet dose, ask your neurologist if you can take the two tablets 10-15 minutes apart. The first tablet you'd take just a a little BEFORE you normally would...and the second just a little AFTER you normally would...about 15 minutes apart may work (AGAIN...ASK YOUR NEUROLOGIST FIRST!)

 

WHY? By dividing up the dose you try to take the first tablet a little early JUST BEFORE your previous dose wears off. It keeps the L-Dopa level from falling too fast or too low....then the second tablet can later "Buoy" up the dose level, BUT avoiding a sharp spike.

 

My father takes a dose of 1 1/2 tablets 6 times a day. He had horrible peak dose dyskinesia, transitional (in between dose) dyskinesias and bad extended "off" periods and drug failure. I began dividing his doses in 3 half tablets, each 10 minutes apart...

HUGE DRAMATIC IMPROVEMENT....70%-80% BETTER IN ALL AREAS

 

I am just writing this because NO Neurolgist advised me about this. IN FACT, they looked at my Dad...and shrugged their shoulders and said , "Well, 12 years with Parkinsons....and....what can you do?"

 

I brought this idea to a great Neurolgist at the Veteran Administration in West Los Angeles and he helped me out line the dosing schedule.

 

Though my father's has it tough, at least this has eased his discomfort some...

REMEMBER, THIS THEORY ADDS NO OTHER NEW DRUGS & SIMPLY FINE TUNES THE SINAMET YOU ARE ALREADY TAKING...IT MAY ALLOW YOU IN THE FUTURE TO TAKE LESS SINAMET...PERHAPS...

Again Ask your Neurolgist...BETTER YET, ASK 3 DIFFERENT ONES AND COMPARE THEIR ANSWERS..ASK QUESTIONS...BE RELENTLESS....OPTIMIZE YOU EXERCISE DIET AND SUPPLEMENTS (VITAMINS, ETC.)AND YOU'LL MAKE PROGRESS

 

Good luck...I hope this helps someone....in the name of my Dad...Ed

Love ya Dad...

 

 

Steve

No longer just for rats. Those Prosavin trials which have had excellent results in Primates are now starting in Humans.

Oxford Biomedica Phase I/II Trial

RNS Number:7953J
Oxford Biomedica PLC
13 December 2007







For Immediate Release 13 DECEMBER 2007



OXFORD BIOMEDICA INITIATES PHASE I/II TRIAL OF PROSAVIN(R) GENE-BASED TREATMENT
FOR PARKINSON'S DISEASE


Oxford, UK - 13 December 2007: Oxford BioMedica (LSE: OXB), a leading gene
therapy company, announced today that it has initiated a Phase I/II trial of
ProSavin, its novel gene-based treatment for Parkinson's disease. This follows
regulatory clearance from the French Health Products Safety Agency (AFSSAPS) of
the Company's Clinical Trial Application. Patient recruitment for the Phase I/II
trial will start immediately. The trial is being conducted at the Henri Mondor
Hospital in Creteil, which is a European centre of excellence for neurosurgery
and a member of the Assistance Publique Hopitaux de Paris (APHP) in France.


The primary objectives of the trial are to assess the safety and efficacy of
ProSavin. The analyses of patients will include the application of advanced
non-invasive neuro-imaging techniques, in collaboration with the Commissariat a
l'Energie Atomique (CEA) and Service Hospitalier Frederic Joliot (SHFJ)/
Molecular Imaging Research Centre (MIRCen) in Orsay, France.


ProSavin uses gene therapy to restore dopamine production in the brain.
Parkinson's disease is caused by the degeneration of dopamine producing nerve
cells, leading to movement impairments. The product uses the Company's
LentiVector(R) system to deliver the genes for three enzymes (tyrosine
hydroxylase, GTP-cyclohydrolase 1 and aromatic amino acid decarboxylase) that
are required for the synthesis of dopamine. ProSavin is administered locally to
the region of the brain called the striatum, converting the target cells into a
replacement dopamine factory within the brain, thus replacing the patient's own
lost source of the neurotransmitter.


Long-term efficacy data in the industry-standard preclinical model of
Parkinson's disease have shown that ProSavin induces almost complete recovery of
movement function and other behavioural measurements. In this model, the
therapeutic effect of ProSavin following a single administration has been
maintained for over 24 months with no diminishment.


Professor Alan Kingsman, Chief Executive of Oxford BioMedica, commented: "The
strength of the preclinical safety and efficacy data with ProSavin has
established strong scientific support for the clinical development of this
pioneering product candidate for Parkinson's disease. If ProSavin's safety and
efficacy profile is replicated in humans, then the product could represent a
fundamentally new approach for the treatment of Parkinson's disease and could
significantly expand the worldwide market for existing therapies, which is
estimated to be approximately US$3 billion."


The Phase I/II trial of ProSavin

ProSavin will be the first gene-based treatment for Parkinson's disease to be
evaluated in a European clinical trial. Patients in the trial will have been
diagnosed with Parkinson's disease and will be failing on current treatment with
L-DOPA but they will not have progressed to drug-induced dyskinesias. It is a
two-stage study. The first stage is an open-label dose escalation to evaluate
two dose levels of ProSavin in cohorts of three patients each. Oxford BioMedica
plans to report preliminary results once the first cohort of patients is
assessable, which is expected in mid-2008. In the second stage of the trial, a
further 12 patients will be recruited to confirm efficacy of the optimal dose.


Current surgical approaches to the treatment of Parkinson's disease require the
destruction of brain tissue or the permanent placement of electrodes in the case
of deep brain stimulation. These treatments have certain limitations and
side-effects. The surgical procedure for administration of ProSavin entails
stereotactic bilateral injection into the striatum under general anaesthesia
using MRI-imaging and mapping. The procedure is designed to be non-destructive
to tissue and does not leave any device in the brain.

The efficacy of ProSavin will be assessed using the Unified Parkinson's Disease
Rating Score (UPDRS). Patients will be monitored at regular intervals, with the
primary endpoint being an efficacy assessment at six months after treatment. The
secondary objective of the trial is to asses the extent to which patients'
current therapy (L-DOPA) can be reduced following administration of ProSavin.


The principal investigator for the trial is Stephane Palfi, MD, PhD, a
neuroscientist at MIRCen/SHFJ-CEA and neurosurgeon at the Henri Mondor Hospital.
Dr. Palfi commented on the start of the trial: "Current standard therapy for
Parkinson's disease is only partially effective in the mid to late stage of
disease and can induce debilitating side-effects after long-term use. ProSavin
has the potential to address this unmet medical need, offering long-lasting
benefit from a single administration. I am very pleased to be involved in the
first clinical trial of this potentially exciting new treatment paradigm for
Parkinson's disease."


Professor Alan Kingsman of Oxford BioMedica added: "We are delighted to have
received a favourable review from the French authorities that allows us to
commence patient recruitment in the Phase I/II trial. This clinical trial of
ProSavin is the culmination of over ten years of research in Oxford BioMedica
and, before that, in Oxford University. It is the first trial using our
proprietary LentiVector technology and, as such, this represents a major event
for Oxford BioMedica and the future of the pipeline of products that use the
same technology."

-Ends-













 

Post Edited By Moderator (yekkimo) : 12/13/2007 6:57:34 AM (GMT-7)

Those Prosavin trials have moved from mouse / primates to men. Trials are taking place in France at present:

Oxford BioMedica (OXB.L):-
A second patient was dosed on ProSavin this week. ProSavin is a gene therapy candidate for the treatment of Parkinson's disease. 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. If there were any safety issues with the first patient, the DSMB would not have allowed the second patient to be dosed.

We understand a second patient has now been dosed on ProSavin as of 15 April 2008.

We ascribe some value to this event as it implies dosing of the first patient was without major safety issues. The phase I trial for ProSavin started dosing patients in March 2008.
Once the first patients are dosed we expect this product to start adding to the technology value embedded in the company. It is worth noting that unlike most other indications,
Parkinson’s disease enjoys the benefits of a highly predictive pre-clinical model, which encourages us on the prospects of ProSavin in clinical trials.

ProSavin is a novel gene therapy approach that utilises the company’s proprietary LentiVector system to deliver three genes (ADDC, TH and CH1) that collectively mediate the conversion of endogenous tyrosine into dopamine. The therapy is designed
to provide long-lasting relief from PD symptoms and is administered via an MRI-guided stereotactic injection into the brain of patients.

Parkinson’s Disease has been touted as a promising target for gene therapy for some time. The therapeutic aim for such a strategy is to introduce genes responsible for dopamine production into cells that populate the area of the brain that is dopamine deficient. The delivered (exogenous) genes are designed to reprogram the transfected cells into kick-starting the production and subsequent release of dopamine – thus
restoring the mechanisms controlling voluntary movement.

Thanks so much to those who took the time to get this information out.  They may be on to something and I am also hopeing that taking the leash off of stem cell research will provide a breakthrough.  The ideas about breaking up the administration of pills makes a lot of sense.  I have not tried one pill followed 10 minutes by another, but I am going to try that although I'm going to have to make myself a meds chart so I can hopefully stay on schedule.  Thanks again.

Stalevo and requip, wow.  Ok, my experience, just facts, no opinion.  Stelevo did nothing for me except make me a bit sleepy.  Requip knocked me out so much that I was not safe driving and I would go to sleep while siting here at the computer.  I also saw bugs which may not have been real.  When the nurse told me to just stop taking Requip I had my first ride in an ambulance.  Do I recommend Requip?  Yeah, I know some people that I would like to give it to.  

       Hi!

    I am Clippercliff, a new member to the forum. I've got PD when I turned 50, now 58

and things don't look much brighter. I've read posts where members talk about cramping

in their legs and feet. That happens to me every day, and is occurring as I write. It is

almost unbearable. My neuro Dr. prescribed clonasapam which has it's own reprocussions.

I find I am depressed and sometimes  turn to gambleing  to occupy my time. When I

 get depressed I think back to my father who had polio when I was 2 yrs. old and passed

away when I was 54,a long time to be paralyzed from the waist down. Unfortunately

it doesn't help the pain go away!! God give me some of my Dad's strength!! 

   I am on carbo levo comtan and requip for meds. Is there anything I can ask my Dr.

to help with the cramping. Thanks to All.

I don't see the benefit of taking two pills ten minutes apart. It seems like you would be taking
more than prescribed. I see my neuro in June and will ask if something new is available.
The P.D. is tollerable, it's the foot cramping that drives me up the wall! Also the exagerated
pain of arthritis in my joints! Clippercliff