Speed is tricky for the next phase, which is to see if it (1) actually affects progress of the disease and (2) is well tolerated long-term. But may it all go smoothly!
ISTR there are statistical techniques which can help, but even so, we're on for a 2-year trial in all likelihood. My neurologist was literally dancing in his chair. :)
It'll be interesting to see if the technique extends to other single-cause conditions.
Imagine having huntingtons, a death sentence hanging over your life, over your family and then suddenly- its cured, the door swings open, and a life you never expected to have lies ahead.
Go team humanity!
It's not exactly cured: "Could slow progress". But of course there is a huge difference between having chances to die 10 years after onset of disease and 30 years! Especially since it appears to start in later life
My family tends to live 25-30 years after onset of symptoms because we have fewer CAG repeats than most HD families. So this may be effectively the same as a cure for us.
To an extent this has happened with Cystic Fibrosis and HIV+ patients. Many have trouble dealing with a future they hadn't prepared for and thought wasn't going to happen.
Living longer is not automatically some magical gift.
I like to think that we're in a golden era where most of these hideous diseases are eradicated or at least made manageable in the next 25 years, with the problem virtually solved in 100 years. Too late for me, but what a world it will be then!
Does anyone have a link to a more technical description of this therapy? From what I've found it's a small anti-sense RNA targeting the mutant huntingtin gene. But I don't see a description of a delivery vehicle, or if there even is one. The drug seems to have pretty big implications if it works, but I'll be frankly amazed if all they had to do was inject the bare nucleic acid into the CSF.
> To determine the distribution and cellular uptake of antisense oligonucleotides (ASOs) delivered by infusion into the CNS, an antibody that selectively recognizes the phosphorthioate
backbone of the ASOs (see Figure S2 A for additional saline controls from the various brain regions) was used to probe coronal sections from the olfactory bulb to the cerebellum (see
Figure S2B for schematic of sectioning and dissections). Following a two week infusion of the HuASO into nontransgenic animals, ASO accumulation was detected in the neurons of most brain regions, including the frontal cortex, striatum, thalamus, midbrain, brainstem, and cerebellum, with the exception of dense regions of white matter and cerebellar granule cells (Figure 2
A). ASOs were also present in neuronal nuclei, cell bodies and neurites, as determined by colocalization of accumulated ASOs with the neuronal marker NeuN (Figure 2B). ASOs also accumulated in nonneuronal cells, including glial fibrillary acidic protein (GFAP)-expressing astrocytes (Figure 2B)
Impressive. An important point here seems to be that these ASO's have a chemically modified backbone which prevents degradation by exonucleases. But the bases are un-modified allowing complimentary pairing and activation of RNAse H activity. Even so, I'm surprised they're able to cross the cell membrane in high enough quantities to have therapeutic effects.
Apparently, these techniques have been around since the mid-nineties or so. TIL...
Here's a link to what I presume is the trial on ClinicalTrials.gov[1]. Notably, the maker, Ionis, is trying this approach on dozens of diseases[2]. I couldn't see a reference about a potential vehicle for the antisense oligonucleotide...
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[ 2.7 ms ] story [ 35.5 ms ] threadGodspeed to everybody working on this...with an emphasis on the “speed” part.
ISTR there are statistical techniques which can help, but even so, we're on for a 2-year trial in all likelihood. My neurologist was literally dancing in his chair. :)
It'll be interesting to see if the technique extends to other single-cause conditions.
The don’t want to dismiss the difference though.
Living longer is not automatically some magical gift.
http://www.cell.com/neuron/pdf/S0896-6273(12)00444-8.pdf
> To determine the distribution and cellular uptake of antisense oligonucleotides (ASOs) delivered by infusion into the CNS, an antibody that selectively recognizes the phosphorthioate backbone of the ASOs (see Figure S2 A for additional saline controls from the various brain regions) was used to probe coronal sections from the olfactory bulb to the cerebellum (see Figure S2B for schematic of sectioning and dissections). Following a two week infusion of the HuASO into nontransgenic animals, ASO accumulation was detected in the neurons of most brain regions, including the frontal cortex, striatum, thalamus, midbrain, brainstem, and cerebellum, with the exception of dense regions of white matter and cerebellar granule cells (Figure 2 A). ASOs were also present in neuronal nuclei, cell bodies and neurites, as determined by colocalization of accumulated ASOs with the neuronal marker NeuN (Figure 2B). ASOs also accumulated in nonneuronal cells, including glial fibrillary acidic protein (GFAP)-expressing astrocytes (Figure 2B)
[1] https://clinicaltrials.gov/ct2/show/NCT02519036?term=ionis&c...
[2] https://clinicaltrials.gov/ct2/results?cond=&term=ionis&cntr...