Gene therapy - Sheffield Institute for Translational Neuroscience

[FrenchFries]

Have scientists found a cure for Professor Stephen Hawking? | Mail Online

 

[Nikki J]

This is of course good news. I wish they shared more about how this works. There has already been a phase 1 trial for sod1 in the US of gene blocking technology. It looked promising but needed to be reformulated
for better efficacy which is currently happening. The same technology is being worked on for c9 which is my genetic defect. For c9 there is also work going on for a small molecule blocking agent

 

[Nikki J]

More info unfortunately. Heard from someone in UK who was in direct contact with Sheffield. This potential therapy for sod1 is several years from possible clinical trials. More journalistic hyperbole

 

[MaxEidswick]

> More journalistic hyperbole

:-(

 

[GregK]

From what I read (and I admit to not having truly 'researched' it) the SOD1 gene is associated with familial ALS, and only applicable to 2% of overall ALS cases...

Is this not correct?

Edit: I found mention in one of the Copper articles that SOD1 is associated with 7% of ALS cases.

So I will hold off on sucking on pennies....

 

[george123]

Just in case link (below) to entire document doesn't work here's page 5, I added the underline, to me it appears to address Greg K's question :

From pre-clinical studies to clinical trials in patients

Our goal is to make our gene therapy safe and effective for human use and ultimately to offer an effective treatment to patients with MND linked to SOD1. Therefore, before entering clinical trials in humans, further pivotal pre-clinical studies are required to prove the safety of our therapy and obtain a license for human use (Biologic License Application (BLA)).

Our results so far: Reducing SOD1 protein levels in the central nervous system

We have been working on optimising dosage and route of delivery of our SOD1 gene therapy (scAAV9-hSOD1si) and have achieved a consistent reduction of SOD1 messenger RNA and protein levels at 2 weeks after treatment. It should be noted that a further reduction of the SOD1 protein would be predicted at later time points beyond 2 weeks.

The next steps in pre-clinical development

1. Evaluation of the effect of reduced SOD1 protein levels in mice following treatment before and at the onset of symptoms as a clinically relevant “ proof of concept”.
2. Providing evidence that our RNAi molecules specifically target the SOD1 gene by screening for potential off-target effects both in vitro and in vivo;
3. Scaling up the production of our therapeutic scAAV9 vector according to guidelines and good manufacturing practice (GMP) for safe medicinal products;
4. Regulatory GLP Toxicology and Biodistribution studies in rodents which will be outsourced to an experienced Contract Research Organisation (CRO);
5. Dosing studies in large animals;
6. Obtaining a Biologic License Application (BLA) to initiate a phase I trial in ALS/MND patients.

How long will it take to start a Phase I trial in humans?

We are hoping to start a first human trial for the gene therapy for SOD1 MND within the next two years.

How will our expertise help to drive this forward?

Prof Azzouz has led the field internationally in developing and ev aluating gene therapy approaches using viral vectors for neurodegenerative diseases. gene therapy in models of Parkinson’s disease (PD) is currently trialled in humans and his new gene therapy for spinal muscular atrophy (SMA) has received “orphan drug designation” from the European Medicines agency and is on its way to a first UK trial in humans in 2015. This therapy uses the same carrier system that will be used for the SOD1 gene therapy (self-complementary adeno-associated v irus serotype 9, short scAAV9). With all the
processes for safety, manufacturing and application already in place, the team will be able to fast-track a gene therapy for SOD1 MND and in succession other genetic disease variants.

How our gene therapy for SMA paves the way

We have already shown that the carrier system optimised for our gene therapy programme at SITraN crosses the blood-brain-barrier and delivers fast, robust, long-lasting gene transfer to the brain and spinal cord. Replacing the faulty survival motor neuron gene that causes SMA with a healthy copy in an SMA mouse model leads to a complete correction of the movement problems in the treated animals; their life span increases from an average of 15 days to more than 300 days.

These data provide evidence for the most efficacious SMA therapy observed in this field to date.

http://sitran.dept.shef.ac.uk/files/4814/0499/6396/110714_SOD1_Briefing_Notes.pdf