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Old 19-08-16, 04:08 PM   #1
Kathy61
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Default Ionis HTTRx Trial

Hi

It looks as though Ionis are recruiting a second wave for their phase 1 / 2 HTTRx trial. It's very exciting as it looks as though the first lot of patients to be dosed have shown it to be safe!


https://clinicaltrials.gov/show/NCT02519036
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Old 19-08-16, 10:15 PM   #2
toosh
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Default Re: Ionis HTTRx Trial

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Originally Posted by Kathy61 View Post
Hi

It looks as though Ionis are recruiting a second wave for their phase 1 / 2 HTTRx trial. It's very exciting as it looks as though the first lot of patients to be dosed have shown it to be safe!


https://clinicaltrials.gov/show/NCT02519036
I note its only UCL London who are recruiting in the U.K
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Old 19-08-16, 11:04 PM   #3
Allan
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Default Re: Ionis HTTRx Trial

.
The current IONIS-HTTRx trial is officially titled:

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 443139 in Patients With Early Manifest Huntington's Disease.

I think I’m right in saying that of the 36 people enrolled for the clinical trial, 30 are based in Canada and 6 in Europe, ie at UCL London. One or two of the 6 UK participants have dropped out since the trial began.

The Inclusion Criteria for participants is:

• Diagnosed with early manifest Huntington's disease
• Male or female, aged 25 to 65 years, inclusive, at the time of informed consent
• Able and willing to meet all study requirements, including travel to Study Centre and participation in all procedures and measurements at study visits
• Have a trial partner who is reliable, competent and at least 18 years of age, is willing to accompany the patient to select trial visits and to be available to the Study Centre by phone if needed
• Able to tolerate MRI scans, blood draws and lumbar punctures
• Reside within 4 hours travel of the Study Centre

This summer, Ionis Pharmaceuticals (formerly Isis Pharmaceuticals), in collaboration with the CHDI Foundation and Roche Pharmaceuticals, began a Phase I trial of the antisense oligonucleotide (ASO) IONIS-HTTRx in Canada and Europe. The trial, named “Safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS-HTTRx in patients with early manifest Huntington's disease,” uses a randomized, placebo-controlled, double-blind design to evaluate the safety and tolerability of ascending doses of IONIS-HTTRx.

Both the active drug and placebo are administered intrathecally at four-week intervals over a 13-week treatment period. If successful in this and subsequent trials, the compound could become the first disease-modifying drug for HD on the market. Gene silencing therapies for HD have long been a promising avenue of exploration. Nucleotide-based gene silencing methods have advanced considerably in recent years, and IONIS-HTTRx is the first tested in human HD patients. By attacking HD near its genetic roots, the drug could potentially reduce, partly reverse, or even prevent the symptoms of HD.

Numerous successes have been reported in rodent models, first with RNA-based compounds, and more recently with ASOs. ASOs are synthetic, modified nucleotide agents designed to bind to a chosen sequence in mRNA using Watson-Crick complementarity. Once bound, several cellular mRNA disposal mechanisms remove the mRNA, repressing gene expression by reducing translation and protein expression. ASO-bound mRNA is degraded by RNAse H prior to splicing and nuclear export. Most trials in animal models have focused on nonselective silencing of both wild-type and mutant HTT alleles, though research into allele selective approaches has also been undertaken.

Directly infused into the brain parenchyma or ventricles of HD-model mice, ASOs appear to significantly reduce mRNA expression and total HTT levels. This has been associated with both slowing of the phenotypic progression of HD, and substantial improvement in some manifestations that have clinically significant counterparts in human HD. The effect of lowering wild-type HTT in humans remains unknown. Though the function of wild-type HTT is not understood, knocking out the gene is lethal to embryos in murine models, and conditional HTT knockout has been reported to produce neurodegeneration. However, using ASOs to knockdown 75% of total huntingtin in BACHD mice produced no detectable behavioural or motor deficits (though subtler effects may not be detectable in murine studies.) The benefits of lowering the pathogenic mHTT protein may significantly outweigh the potential side effects of lowering the wild-type protein.

Taken from: http://huntingtonstudygroup.org/wp-content/uploads/2016/05/HD-Insights-Vol.-13-CORRECTED_Retraction_FINALMay4.pdf

Also, on the Huntington’s disease UK facebook page and elsewhere, the usual thing has happened with someone posting a link, thinking it current, whereas the trial actually got the go-ahead on 19th October 2015: http://hdresearch.ucl.ac.uk/current-studies/huntingtin-lowering-trial

Still a long way to go then …

.
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Old 21-08-16, 08:56 PM   #4
wanda the mermaid
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Default Re: Ionis HTTRx Trial

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Originally Posted by Kathy61 View Post
Hi

It looks as though Ionis are recruiting a second wave for their phase 1 / 2 HTTRx trial. It's very exciting as it looks as though the first lot of patients to be dosed have shown it to be safe!


https://clinicaltrials.gov/show/NCT02519036
It does seem very exciting and at least gives a glimmer of hope for my family.
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