antisense
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tdamess
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experimental therapy using an approach known as antisense, in which a drug is designed to shut down the RNA (Ribonucleic acid) that is responsible for the production of disease-causing proteins, is being prepared for a clinical trial in people with a familial form of ALS later this year. and it say's to find we can find out more at als.org but i just wanted to know what others think
tdamess
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we do not have als family wise but, are they trying to see if there is a connection between als, parkins, and hunting's as my uncle and his son ( my cousin ) died of hunting's
halfin
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I'm sorry, but this approach makes no sense to me!
That was a joke. I've been trying to resist all day but it's no use.
To apologize for that bad joke I will comment on this antisense therapy. As I understand it, the idea is to block the "messenger RNA" (mRNA) which carries instructions from the genes in the cell nucleus out to the ribosomes in the outer part of the cell. The ribosomes read the mRNA and create proteins. People with the bad SOD1 gene mutation create defective SOD1 proteins which somehow cause or at least promote ALS. Therefore if you can block or at least reduce the mRNA for the SOD1 gene, you would have less of the harmful SOD1 proteins and a healthier cell. Antisense is a drug which binds to and neutralizes specific mRNA. They will create antisense for the mRNA for the bad SOD1, inject it into the spinal region, and it should hopefully reduce the harmful SOD1 and extend life. This has been tested in ALS rats with good effect. (I think they used rats rather than mice because it is easier to do a spinal tap on rats than mice, and you need that to get the medicine into the spinal cord.)
So I see some pros and cons here. On the positive side, the theory is good and it did help the rats. Technology exists for long-term attachments for pumping drugs into the spinal cord area, often used for chronic pain relief. If the results are effective, they hope that they can figure out other kinds of proteins that may be bad in other ALS patients, and eventually help more people.
On the con side, only 10% of PALS are familial, and only 20% of familial cases are due to SOD1 mutation. That is only 2% of PALS. If I have worked my math right, that is only about 600 people in the whole United States who are even candidates for this. And they have to agree to have this rather invasive spinal pump installed, potentially for a long time. So I imagine it will be hard to recruit enough people for a good study. Also, unfortunately most therapies that have worked on ALS mice haven't worked on people, so we can't get our hopes up too much. Then even if it does work, there has not been much success in identifying bad genes in sporadic ALS so it does not seem too likely that there will be good antisense target genes for most PALS.
Still, even with these problems, it is certainly worth trying this new approach. If it does work, that would be the first good news in many years in terms of ALS therapy.
Also I can't help thinking that many more therapeutic agents might be effective if they would use this concept of injecting straight into the spinal region. Obviously it is much more invasive and perhaps dangerous, but it would be so easy to get any kind of therapeutic agent like glutathione or nerve growth factors right where they are needed. Half the time with these drugs, barely any gets to the nerve cells, and this would solve that problem.
That was a joke. I've been trying to resist all day but it's no use.
To apologize for that bad joke I will comment on this antisense therapy. As I understand it, the idea is to block the "messenger RNA" (mRNA) which carries instructions from the genes in the cell nucleus out to the ribosomes in the outer part of the cell. The ribosomes read the mRNA and create proteins. People with the bad SOD1 gene mutation create defective SOD1 proteins which somehow cause or at least promote ALS. Therefore if you can block or at least reduce the mRNA for the SOD1 gene, you would have less of the harmful SOD1 proteins and a healthier cell. Antisense is a drug which binds to and neutralizes specific mRNA. They will create antisense for the mRNA for the bad SOD1, inject it into the spinal region, and it should hopefully reduce the harmful SOD1 and extend life. This has been tested in ALS rats with good effect. (I think they used rats rather than mice because it is easier to do a spinal tap on rats than mice, and you need that to get the medicine into the spinal cord.)
So I see some pros and cons here. On the positive side, the theory is good and it did help the rats. Technology exists for long-term attachments for pumping drugs into the spinal cord area, often used for chronic pain relief. If the results are effective, they hope that they can figure out other kinds of proteins that may be bad in other ALS patients, and eventually help more people.
On the con side, only 10% of PALS are familial, and only 20% of familial cases are due to SOD1 mutation. That is only 2% of PALS. If I have worked my math right, that is only about 600 people in the whole United States who are even candidates for this. And they have to agree to have this rather invasive spinal pump installed, potentially for a long time. So I imagine it will be hard to recruit enough people for a good study. Also, unfortunately most therapies that have worked on ALS mice haven't worked on people, so we can't get our hopes up too much. Then even if it does work, there has not been much success in identifying bad genes in sporadic ALS so it does not seem too likely that there will be good antisense target genes for most PALS.
Still, even with these problems, it is certainly worth trying this new approach. If it does work, that would be the first good news in many years in terms of ALS therapy.
Also I can't help thinking that many more therapeutic agents might be effective if they would use this concept of injecting straight into the spinal region. Obviously it is much more invasive and perhaps dangerous, but it would be so easy to get any kind of therapeutic agent like glutathione or nerve growth factors right where they are needed. Half the time with these drugs, barely any gets to the nerve cells, and this would solve that problem.
tdamess
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so in my terms they kinds have the right idea but, wrong med's... that's all i wanted is thoughts on this and you did explain this very well , i wonder now if they do have an answer but, not given at high enough doses such as glutathione ... as with the way joelc had to do it ...it was considered an overdose . and, it worked for him....thank you
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