Research Briefs: FA, MG, MM, MMD1, gene therapy

Research items about Friedreich's ataxia, myasthenia gravis, mitochondrial myopathies, type 1 myotonic dystrophy, gene therapy and gene modification

Article Highlights:
  • Edison Pharmaceuticals is developing treatments for Friedreich's ataxia and mitochondrial diseases.
  • Intravenous immunoglobulins and plasmapheresis appear equally effective in adults with myasthenia gravis.
  • A molecule called ABP1 may provide a new lead in treating type 1 myotonic dystrophy.
  • A new "cut-and-paste" approach could improve gene therapy.
  • Scientists have developed a new strategy for overcoming "premature stop codon" mutations, a common cause of genetic disease.
by Margaret Wahl on July 7, 2011 - 10:28am

Edison drugs target FA, mitochondrial diseases

Edison Pharmaceuticals, a biotechnology company, announced in June 2011 that its experimental drug EPI-A0001 has shown promise in a 28-day, placebo-controlled trial in people with Friedreich's ataxia (FA). (See Edison Pharmaceuticals Announces Results of EPI-A001 Phase 2A Double-Blind, Placebo-Controlled 28-Day Clinical Trial.)

In this phase 2a trial, there was improvement in the Friedreich's Ataxia Rating Scale scores in those taking the low and high dose of EPI-A0001 in comparison to those taking a placebo.

The company also announced in June that its experimental drug EPI-743, designed to treat mitochondrial diseases, is available for certain patients with these diseases in a special "expanded access" program. (See Edison Pharmaceuticals to Provide Expanded Access to EPI-743 for Mitochondrial Disease.)

Edison is also studying EPI-743 in a clinical trial in mitochondrial diseases. (See EPI-743 for Mitochondrial Respiratory Chain Diseases; or search for trial NCT01370447 on

Edison's products are designed to improve the function of mitochondria, the energy-producing parts of cells. Mitochondria are affected in a number of diseases, including FA.

IVIG, plasmapheresis equally effective in adults with MG

A 28-day study of 84 adults with moderate to severe myasthenia gravis (MG) who were randomly assigned to receive intravenous immunoglobulins (IVIG) or plasmapheresis (also called plasma exchange) has found that the treatments are equally effective, that both are well-tolerated, and that the duration of benefit is about the same.

The study, published June 7, 2011, in Neurology, noted that people with MG who have more severe weakness and antibodies to acetylcholine receptors may respond better to these treatments than other patients. (See Comparison of IVIg and PLEX in patients with myasthenia gravis.)

Acetylcholine receptors, located at the junction of nerve and muscle fibers, are the targets of immune-system attack in many people with MG. IVIG and plasmapheresis are procedures designed to modify the immune response, as are several medications used to treat MG.

New lead found in search for MMD1 (DM1) treatment

MDA grantee Ruben Artero at the University of Valencia in Spain was part of a research group that recently identified a new way to block a disease-causing genetic mutation underlying type 1 myotonic dystrophy (MMD1, or DM1).

The experiments were conducted in a fly model of the disease, but the researchers say that the blocking molecule they've identified, called ABP1, "represents a promising approach in the generation of new effective treatments for DM1."

The scientific paper was published online July 5, 2011, in Proceedings of the American Academy of Sciences. (See In vivo discovery of a peptide that prevents CUG-RNA hairpin formation and reverses RNA toxicity in myotonic dystrophy models.)

See also Disrupted Disease Process for a related article about a potentially therapeutic molecule identified in 2009 in a mouse model of MMD1.

'Genome editing' seen as next step for gene therapy

A new type of gene therapy that precisely "edits" genetic information like a word-processing program, inserting functional DNA and removing nonfunctional DNA at a precise location, has successfully treated the blood-clotting disorder hemophilia in a mouse model of this disease. The new approach may prove safer and more effective than those now in use as gene therapy strategies. The findings were reported online June 26, 2011, in Nature. (See In vivo gene editing restores haemostasis in a mouse model of haemophilia.)

Current approaches to gene therapy supply a functional version of a faulty gene without causing its integration into a chromosome, which can limit the effectiveness of the therapy; or result in integration of the new gene into a chromosome at an unpredictable location, which can be extremely dangerous.

The new approach delivered enzymes called zinc finger nucleases that cut DNA in a precise location and at the same time delivered replacement genes. The cut made by the enzymes appears to stimulate a cellular repair mechanism that swaps the replacement DNA for the existing, defective DNA, in a "cut-and-paste" maneuver.

In this case, the replacement DNA was for factor 9, a clotting protein, given to mice deficient in this protein because of a genetic mutation. The mice that received the combination of targeted zinc finger nucleases (ZFNs) and factor 9 genes produced enough of the clotting factor to restore nearly normal blood clotting.

The investigators say that the results of their "ZFN-driven gene correction" experiments raise the possibility of genome editing as a "viable strategy for the treatment of genetic disease."

For an article about this paper from Children's Hospital of Philadelphia, see Genome Editing, A Next Step in Genetic Therapy, Corrects Hemophilia in Animals.

New approach developed for stop codon read-through

Scientists at the University of Rochester (N.Y.) Medical Center have identified a new approach to stop codon read-through, a gene-modification technique, that could ultimately help an uncertain percentage (possibly as many as a third) of people with genetic diseases. (See Converting nonsense codons into sense codons by targeted pseudouridylation for the scientific paper; and Protein synthesis: Stop the nonsense for an accompanying editorial. Both were published June 16, 2011, in Nature.)

For a news story about these findings from the University of Rochester Medical Center, see Changing Genetic 'Red Light' to Green Holds Promise for Treating Disease.

Stop codon read-through is based on the idea that many cases of genetic disease are caused by premature stop codons, also called nonsense mutations, which instruct cells to stop making a protein too soon, before protein synthesis is complete. It's been estimated that up to 15 percent of people with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) have the disease because of a premature stop codon in the gene for the dystrophin protein.

The newly developed approach to stop codon read-through alters the genetic instructions at the level of RNA, the chemical step between DNA and protein synthesis, so that a premature stop codon is no longer read as a signal to stop protein synthesis.

Other approaches to stop codon read-through include the experimental drug ataluren, in development by PTC Therapeutics (see Low-Dose Ataluren Shows Some Benefit in DMD/BMD); and a different strategy in development by MDA grantee Carmen Bertoni at the University of California, Los Angeles (see UCLA Researcher Receives MDA Grant to Develop DMD Drug.)

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