Hi Guys - I started doing some research about ProSavin yesterday.  I have a call into Oxford BioMedica and hope to hear from them Monday, at which point I will update.  For now...

Sky News reported this week on the results of ProSavin, a new gene therapy from Oxford BioMedica that may revolutionize PD therapy.  The results are extremely encouraging, though only 15 people have been treated with ProSavin.  
ProSavin uses a virus to deliver three enzymes directly to the striatum via injection, and is a one-time therapy. ProSavin is the only gene therapy currently in trial that aims to reproduce dopamine in the brain, other therapies are aimed at protecting dying cells. 
From the Oxford BioMedica website:
ProSavin is an innovative gene-based treatment for Parkinson’s disease, a progressive movement disorder.  In Parkinson’s disease, there is degeneration of the cells in the brain that produce dopamine.  Using Oxfort BioMedica’s LentiVector gene delivery technology, ProSavin delivers the genes for three enzymes that are required for the synthesis of dopamine directly to the region of the brain called the striatum, converting cells into a replacement dopamine factory within the brain, thus replacing the patient’s own lost source of the neurotransmitter.
The three enzymes delivered by ProSavin are  AADC, TH and Ch1-GTP.  AADC is aromatic l-amino acid decarboxylase.  AADC catalyzes L-DOPA to dopamine, and is inhibited by Carbidopa outside of the blood brain barrier to inhibit the premature conversion of L-DOPA to Dopamine.
TH is tyrosine hydroxylase.  TH also catalyzes the formation of L-DOPA.  In fact, in one study Haavik and Toska characterized PD as “a tyrosine hysdorxylase-deficiency syndrome of the striatum. 
The third enzyme, CH1-GTP is a co-factor required for the biosynthesis of dopamine.  GTP is encoded by the gene GCH1, mutations in which are associated with levodopa-responsive dystonia. 
These three enzymes are delivered by  Oxford BioMedica’s LentiVector technology.  Again from their site:
The LentiVector gene delivery technology is designed to overcome the safety and delivery problems associated with earlier generations of vector systems.  The technology can stably deliver genes into cells with up to 100% efficiency and can integrate genes into non-dividing cells, including neurons in the brain and retinal cells in the eye.  In such cell types, studies suggest that gene expression could be maintained indefinitely.  It also has a larger capacity than most other vector systems and can accommodate multiple therapeutic genes.
Four cohorts have currently been enrolled in the ProSavin studies, each with escalating doses via the LentiVector technology.  Chort One received four needle injections per brain hemisphere, with 1X dose. Cohort Two received five needle injections per hemisphere, with 2x dose. Cohort Three received three needle injections with 2x dose, and Cohort Four 3 needle injections with 5x dose.  
These Four Cohorts represent a Phase I/II trial, a phase designed to assess the safety and efficacy of the drug. Together, the Cohort studies represent two does levels and an enhanced administration technique.  The Fourth Cohort is receiving the scaled equivalent of the optimal dose. 
Oxford BioMedica is reporting two-year data.  The first two dose levels were safe and well-tolerated in all patients, with encouraging clinical benefit.  The Fourth Cohort is reporting at three months and showing average motor function improvement of 29%.  The Third Cohort is reporting at six months, and showing improved motor function of 61%.  Oxford BioMedica now plans placebo-controlled studies and a randomized Phase II trial for this year. 
Patients have remained on oral L-DOPA therapy, but across the first three cohorts, oral medications have either been reduced or remained stable, and quality of life has either increased or remained stable. 
ProSavin trials are currently being conducted at two locations, the Henri Mondor Hospital in Paris and the Adenbrookes Hospital in Cambridge, UK.  They are currently recruiting for trials at both locations and seeking mid-stage disease patients who are losing ground with oral therapies. Get more information at [log in to unmask]



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