Muscles need dystrophin in order to regenerate. Persons suffering from Duchenne muscular dystrophy lack this essential muscular protein due to mutations in the gene which is responsible for producing dystrophin. As a result, their existing muscle cells deteriorate over time and are gradually replaced by connective and fatty tissue; muscle strength weakens during the course of the disease. The first symptoms usually appear around the age of five. Children with the disease begin to have difficulties with movements they previously completed with ease, for example climbing stairs or getting up from the floor. At approximately the age of twelve, they are no longer able to walk, later losing movement in their arms and hands. Due to concomitant respiratory and cardiac failure, the majority of patients does not reach the age of 40. DMD affects mainly boys, since the responsible mutations are located in the dystrophin gene on the X chromosome.
Gene scissors remove defective gene sequence
An interdisciplinary Munich research team led by scientists from TUM has for the first time succeeded in correcting the mutated dystrophin gene in living pigs. In order to cut the defective gene sequence from the DNA of the animals’ muscle and heart cells, the researchers modified the Crispr-Cas9 gene scissors. “These gene scissors are highly efficient and specifically corrected the dystrophin gene,” says Prof. Wolfgang Wurst, developmental geneticist at TUM and the German Research Center for Environmental Health. It became then again possible to viably read the gene which had been unreadable because of the genetic defect, thus allowing for a successful protein biosynthesis. Now the shorter but stably formed dystrophin protein was able to improve muscle function. The animals treated were less susceptible to cardiac arrhythmia and had an increased life expectancy compared to animals with the disease that did not receive the therapy.
A permanent therapy
“Muscle and heart cells are long-lived cell structures. One half of all myocardial cells remain functional from birth throughout the entire lifecycle of a human being,” says Prof. Christian Kupatt, cardiologist at university hospital TUM Klinikum rechts der Isar. “The genome of a cell is used for protein biosynthesis as long as the cell is alive, and once a cell has been affected by the therapy, it remains corrected. So if we change the genome of a myocardial cell, the correction is a long-term success, in contrast to the results of previous methods.”
Therapeutic success with clinically relevant model
The gene sequence responsible for the dystrophin protein has already been successfully corrected in the past, however in mice and other animal models. “Our results are very promising, since for the first time, we have now been able to demonstrate therapeutic success in a clinically relevant large animal model,” says Prof. Maggie Walter, neurologist at the LMU university hospital. In terms of important biochemical, clinical and pathological changes, the pig model mirrors Duchenne muscular dystrophy in humans. “Since the disease proceeds faster in our pig model, we were able to verify the efficacy of the therapeutic approaches within a manageable period of time,” says Prof. Eckhard Wolf, LMU specialist in veterinary medicine.
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
Duchenne muscular dystrophy
- FDA OKs Targeted Tx for Duchenne Muscular Dystrophy Mutationon February 26, 2021 at 2:29 am
The FDA approved injectable casimersen (Amondys 45) as a targeted treatment Duchenne muscular dystrophy (DMD) in patients with a confirmed DMD gene mutation amenable to exon 45 skipping. “Developing ...
- FDA approves Sarepta drug for muscular dystrophy with rare genetic mutationon February 25, 2021 at 4:32 pm
The FDA decision gives Sarepta Therapeutics its third approved drug for Duchenne muscular dystrophy. The accelerated approval requires the biotech to conduct additional clinical testing to confirm the ...
- FDA OKs First 'Targeted Treatment' for Rareon February 25, 2021 at 3:41 pm
The FDA has approved casimersen (Amondys 45) injection for treating patients with both Duchenne muscular dystrophy (DMD) and a rare mutation of the DMD gene.
- MDA Celebrates FDA Approval of Amondys 45 for Treatment of DMD Amenable to Exon 45 Skippingon February 25, 2021 at 2:54 pm
MDA Celebrates FDA Approval of Amondys 45 for Treatment of DMD Amenable to Exon 45 SkippingPR NewswireNEW YORK, Feb. 25, 2021Fourth approved exon-skipping therapy for Duchenne muscular dystrophyNEW ...
- Another Duchenne Treatment Gets FDA Nodon February 25, 2021 at 2:32 pm
Casimersen (Amondys 45) is approved to treat Duchenne muscular dystrophy (DMD) patients with a confirmed mutation amenable to exon 45 skipping, the FDA announced Thursday. Like two other exon-skipping ...
Go deeper with Google Headlines on:
Duchenne muscular dystrophy
Go deeper with Bing News on:
Gene correction therapy
- RNA-targeted Splice-correction Therapy for Neuromuscular Diseaseon February 19, 2021 at 4:00 pm
Splice-modulation therapy, whereby molecular manipulation of premessenger RNA splicing is engineered to yield genetic correction ... reading-frame in the DMD gene leading to the absence of ...
- NovalGen announces updates to its executive management teamon February 19, 2021 at 4:42 am
London, United Kingdom, 19 February 2021 – NovalGen Ltd (“NovalGen”), a biopharmaceutical company developing breakthrough cancer therapies, today announced updates to its management team. NovalGen is ...
- Gene Therapy in a Patient with Sickle Cell Diseaseon February 17, 2021 at 4:00 pm
Gene therapy for patients with this disorder is ... without recurrence of sickle crises and with correction of the biologic hallmarks of the disease. (Funded by Bluebird Bio and others; HGB ...
- Retroviral Vectors for Gene Therapyon February 16, 2021 at 4:00 pm
vectors have now been used in more than 350 gene-therapy studies. Retroviral vectors are particularly suited for gene-correction of cells due to long-term and stable expression of the transferred ...
- M6P Therapeutics Presents Promising Preclinical Data in Lysosomal Storage Disorders at the 17th Annual WORLDSymposium 2021on February 12, 2021 at 1:00 am
M6P Therapeutics, a privately held life sciences company developing next-generation recombinant enzyme and gene therapies for lysosomal storage disorders (LSDs), announced today the presentation of ...