New Novel Drug – Testing in Myotonic Dystrophy – Isis

Recently Isis Pharmaceuticals gave a talk at the myotonic dystrophy foundation conference in San Fransisco, CA. This talk including just information that had been publicly given out previously. However, one of the lead researchers in the Myotonic Dystrophy field commented that this new drug that Isis is pursuing in collaboration with Biogen could be the “Fountain of Youth Drug”. The basic mechanism of antisense technology, if aging is caused by cell clogging with these proteins that are not being released to proper area. This could be a hug huge blockbuster drug that would exceed everyone potential.

Here is the information From Dr. McCleod, Director of Research at Isis Pharmaceuticals at the Conference:

What is the New Drug:  Antisense molecules. These are small DNA molecules that are 12-20 molecules. They are designed to bind with the repeats and inactivate them.

The Testing  The drug was tried in mice with great success. It seemed to work in the liver and kidneys but they looked for skeletal muscle in particular.

How Much Drug? The injections were 50mg/Kg/week, 2X injections for 4 weeks. It is likely that two injections will be needed one for the body and a second in the spinal fluid as the drug does not penetrate the blood brain barrier

The Results: 4 muscles were looked at and 80-90% inhibition of 3 types of muscles. The toxic RNA that was being retained in the cell decreased. The drug was retained in the cells. The therapy was effective for over a year. In effect the effects are rapid, results are seen within two weeks and Durable with the long lasting effect. Okay so this looks like a hugely successful great drug in Mice. But will it work in humans???

Next Steps: Testing in monkey’s  is slated for 2013 and Humans the earliest would be in 2014, but that optimistic I think. This study was published in June which means the researchers have had months to work on the next steps. Unfortunately everything moves very very slow in the medical world as they have to comply with numerous and cumbersome FDA rules and regulations. And that raises costs tremendously.

Costs: Drugs are very costly. It costs over $100 Million to develop this drug. That is a very conservative estimate. This is why the final cost  of the drug will be high. But there are over 40,000 people with this disease in North America. If the drug costs $10,00 per injection (2 needed one for body and one for brain) The market potential in North America alone is about $800 million per year.

Here is the abstract from the actual study that was published in August 2012
Targeting nuclear RNA for in vivo correction of myotonic dystrophy


Antisense oligonucleotides (ASOs) hold promise for gene-specific knockdown in diseases that involve RNA or protein gainoffunction effects. In the hereditary degenerative disease myotonic dystrophy type 1 (DM1), transcripts from the mutant allele contain an expanded CUG repeat1, 2, 3 and are retained in the nucleus4, 5. The mutant RNA exerts a toxic gainoffunction effect6, making it an appropriate target for therapeutic ASOs. However, despite improvements in ASO chemistry and design, systemic use of ASOs is limited because uptake in many tissues, including skeletal and cardiac muscle, is not sufficient to silence target messenger RNAs7, 8. Here we show that nuclear-retained transcripts containing expanded CUG (CUGexp) repeats are unusually sensitive to antisense silencing. In a transgenic mouse model of DM1, systemic administration of ASOs caused a rapid knockdown of CUGexp RNA in skeletal muscle, correcting the physiological, histopathologic and transcriptomic features of the disease. The effect was sustained for up to 1 year after treatment was discontinued. Systemically administered ASOs were also effective for muscle knockdown of Malat1, a long non-coding RNA (lncRNA) that is retained in the nucleus9. These results provide a general strategy to correct RNA gain-of-function effects and to modulate the expression of expanded repeats, lncRNAs and other transcripts with prolonged nuclear residence.



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1 thought on “New Novel Drug – Testing in Myotonic Dystrophy – Isis

  1. Excellent summary from the meeting. In a filing today Marina Biotech mentioned they had a pre-clinical candidate for myotonic dystropy. It was the first I had heard of it. Have you heard anything about this Marina compound? Thanks. Here is a link to the filing:

    “The Marina Biotech pipeline currently includes a clinical program in Familial Adenomatous Polyposis (a precancerous syndrome) and two preclinical programs — in bladder cancer and myotonic dystrophy.”

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