RNA illustration (Research.gov)
Update: 15 January 2015. Comments on the article are offered at the end of the main text.
14 January 2015. A clinical trial is underway testing safety and effectiveness of synthetic RNA treatments for Duchenne muscular dystrophy, a genetic disease affecting primarily males. The treatments are developed by Sarepta Therapeutics Inc., a biotechnology company in Cambridge, Massachusetts, and tested at medical centers in the France, Italy, and the U.K.
Duchenne muscular dystrophy is a rare genetic disorder resulting in muscle degeneration and weakness, primarily in the shoulders, arms, hips, and thighs. The disease affects mainly boys starting at age 3 to 5, and caused by a defective gene that fails to produce the protein dystrophin for strengthening muscle fiber and protecting muscles from injury.
Sarepta’s technology designs synthetic proteins resembling RNA, amino acids produced by the genome that send signals containing genetic codes for the functioning of human cells. These synthetic proteins, called phosphorodiamidate morpholino oligomers, or PMOs, are designed to correct malfunctioning genes causing genetic disorders, in this case Duchenne muscular dystrophy.
The specific PMO tested in the clinical trial, code-named SRP-4053, is designed to correct for a gene that prevents production of dystrophin. SRP-4053 acts as a substitute RNA protein with instructions for cells omitting a genetic mutation that prevents dystrophin production. Skipping this mutation, at a specific link in the genetic chain known as exon-53, is believed to enable muscle cells to produce dystrophin, and thus function properly.
Sarepta says the clinical trial began dosing its first patients, boys age 6 to 15 with Duchenne muscular dystrophy, at medical centers in Paris, Rome, London, and Newcastle in the U.K. The trial is conducted by a consortium funded by the European Union testing therapies for Duchenne muscular dystrophy skipping the exon-53 mutation.
The study aims to enroll 48 patients, both with and without a malfunctioning exon-53 gene. Half of the group — those with a malfunctioning exon-53 gene — will receive one of two different doses of SRP-4053 or a placebo. The other 24 patients, without the mutation, will not be treated. The trial is looking primarily at the safety of SRP-4053 as measured by adverse rections to the treatments, as well as efficacy indicators including percentage of muscle fibers with dystrophin and walking ability, measured at 12 and 48 weeks.
SRP-4053 is Sarepta’s second RNA therapy designed to skip mutations associated with Duchenne muscular dystrophy. The company’s lead experimental drug with the brand-name eteplirsen, designed to generate proteins that skip mutations at exon 51, is in intermediate-stage clinical trials.
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Update: Jon Moulton of Gene Tools LLC offers the following comments …
The article states:
“Sarepta’s technology designs synthetic proteins resembling RNA, amino acids produced by the genome that send signals containing genetic codes for the functioning of human cells.”
Sarepta’s Morpholino oligos are not synthetic proteins. They are non-natural molecules that resemble the nucleic acids RNA or DNA. Amino acids are not produced by the genome, though the genetic code specifies the sequence of amino acids that will be assembled into proteins by the ribosome. Amino acids are produced by proteins (we humans lack the ability to produce some of the amino acids and must get them nutritionally).
This sentence is true:
Sarepta’s technology designs synthetic molecules resembling RNA, nucleic acids produced by the genome that send signals containing genetic codes for the functioning of human cells.
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The article states:
“These synthetic proteins, called phosphorodiamidate morpholino oligomers, or PMOs, are designed to correct malfunctioning genes causing genetic disorders, in this case Duchenne muscular dystrophy.”
Morpholinos are not proteins.
This sentence is true:
These synthetic molecules, called phosphorodiamidate morpholino oligomers, or PMOs, are designed to correct malfunctioning genes causing genetic disorders, in this case Duchenne muscular dystrophy.
————————————–
The article states:
“SRP-4053 acts as a substitute RNA protein with instructions for cells omitting a genetic mutation that prevents dystrophin production.”
There is no “RNA protein” involved. Morpholinos do not cause the mutation to be omitted, but eliminate a section of RNA near the mutation to restore dystrophin production.
This sentence is true:
SRP-4053 binds to the RNA made from the mutated dysrophin gene and rearranges RNA splicing to produce an RNA with useful instructions for a functional dustrophin protein.
Read more:
- Biogen Idec, Columbia to Partner on Genetics Research
- RNA Therapies Company Gains $450M in Venture Funds
- Pfizer, Biotech Partner on Hemophilia B Gene Therapy
- Roche Acquiring RNA Medications Biotech Company
- Orphan Status Assigned to Kidney Disorder RNA Therapy
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