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Manchester plays role in trial of new innovative drug for Huntington’s disease

First patients dosed with 'gene silencing' drug, ISIS-HTTRx, for Huntington's disease. Trial of the innovative drug, developed by Isis Pharmaceuticals, aims to reduce production of the toxic protein that causes devastating brain disease.

The first few patients in London and Vancouver have received doses of an experimental RNA-targeting drug for Huntington's disease, it was announced today.

The trial aims to test the safety of an experimental drug known as ISIS-HTTRx, discovered and developed by Isis Pharmaceuticals. Administered by injection into spinal fluid to improve its delivery to the brain, the drug is the first tested in patients that targets the known cause of the disease: a toxic protein called mutant huntingtin which slowly damages and kills neurons, leading to the progressive and ultimately fatal decline in mental and physical abilities that is the devastating hallmark of Huntington's disease.

Dr David Craufurd, Consultant in Neuropsychiatric Genetics at the Manchester Centre for Genomic Medicine (MCGM) will lead the Manchester arm of the study, which is currently in set-up at Saint Mary's Hospital. Dr Craufurd leads the MCGM's specialist Huntington's disease service, which provides genetic counselling services and specialist multidisciplinary clinics for families and individuals affected by Huntington disease (HD).

The MCGM HD management clinic serves a population of more than 250 affected individuals in Greater Manchester and Lancashire, and is a major centre for clinical research in HD; MCGM's patients are currently participating in approximately 10 clinical trials or related clinical research projects.  It is anticipated that the Manchester part of this study will start early in 2016. Only local patients who have been previously followed at the MCGM are currently being considered for this study.

The huntingtin gene and its lethal protein product have been the focus of intense research across the world since their discovery in 1993. 'Gene silencing' drugs, also known as 'antisense' drugs, are designed to reduce production of a chosen protein by attaching to the mRNA 'message molecule' that's made whenever a gene is activated. ISIS-HTTRx targets the huntingtin message molecule, telling the cell to dispose of it, thereby reducing production of the mutant huntingtin protein.

There are no treatments to prevent, slow or cure Huntington's. RNA-targeting antisense drugs, like ISIS-HTTRx, that lower huntingtin production are widely considered the most promising therapeutic strategy currently under investigation. Isis's Huntington's disease therapeutics underwent over a decade of refinement and preclinical testing before human trials could begin. The first Phase 1/2a trial is focused principally on safety, using slowly increasing doses of ISIS-HTTRx with careful monitoring of patient wellbeing, scans and laboratory parameters. In addition, the researchers will be looking for chemical signs that the drug is having the desired effect - by measuring the level of mutant huntingtin protein in the cerebrospinal fluid using a newly developed assay.

The trial is set to recruit patients with very early symptoms of Huntington's from six centres in Europe and Canada:  University College London, London, United Kingdom; University of Manchester, St. Mary's Hospital, Manchester, United Kingdom; Cambridge University Hospital, Cambridge, United Kingdom; Ulm University Hospital, Ulm, Germany; Ruhr-University of Bochum, Bochum, Germany; University of British Columbia, Vancouver, Canada.

Prof Sarah Tabrizi, director of the Huntington's Disease Centre at University College London's Institute of Neurology, is the global chief clinical investigator of the trial.

I'm thrilled that this antisense drug has now been safely administered to the first patients. Families ravaged by Huntington's disease have been waiting for this milestone for decades. I look forward to ensuring the smooth running of this first trial and hopefully seeing ISIS-HTTRx through to efficacy testing and licensing.

Isis Pharmaceuticals has partnered with Roche to develop ISIS-HTTRx to treat Huntington's disease. C. Frank Bennett, Ph.D., senior vice president of research at Isis Pharmaceuticals, said:

Antisense drugs have great potential for many neurodegenerative diseases because they can be tailored to modify the production of any target protein. Huntington's is ideally suited to this innovative therapeutic technology because it comes with genetic certainty: everyone with the mutant gene will get the disease at some point.  We designed ISIS-HTTRx to target the huntingtin gene and reduce the production of huntingtin protein, which is the known cause of the disease.  This approach has the potential to prevent or slow the progression of this disease. If this first-in-human trial proves the drug is safe, we look forward to continuing our successful partnership with Roche to bring the drug to market.

Cath Stanley, Chief Executive of the Huntington's Disease Association of England and Wales, welcomed the news that the first doses of ISIS-HTTRx had been given to Huntington's patients.

As well as being desperate for good news, the Huntington's community is uniquely well-informed and engaged with progress in research across the world,
RNA-targeting approaches are especially exciting because they tackle the problem at its source - the production of the mutant huntingtin protein. The ISIS-HTTRx trial has been eagerly awaited for many years and we hope that the news from the trial continues to be positive.

Any enquiries relating to this announcement should be submitted to Isis Pharmaceuticals' Media Relations or Patient Relations departments through the Information Request page at its website (www.isispharm.com).