Good news! Amazing stuff!
"Faulty versions of the LMNA gene can cause a wide range of health problems, including heart muscle disease (dilated cardiomyopathy) and muscle weakness (muscular dystrophies). Many of these diseases are caused by single-point mutations, which are changes to one DNA "letter" (base). Treatments include physical therapy and lifelong medication, but there are currently no cures. That could change following the work of a team of scientists who have developed and successfully tested a gene editing technique to correct the underlying genetic mutations.
Researchers led by Eric Olson at the University of Texas Southwestern Medical Center used a method called base editing, which has been used previously to correct other genetic heart diseases, but never before on these specific LMNA mutations. Unlike older editing tools, which create double-strand breaks in the DNA, base editing works like a "pencil" and "eraser" to change a single base in a patient's genome. ..."
From the significance and abstract:
"Significance
Point mutations in the Lamin A (LMNA) gene cause devastating human diseases that preferentially affect skeletal muscles and the heart. There is currently no cure for these conditions, and existing therapies are designed to mitigate the symptoms. Base editors represent a powerful approach to correct disease-causing point mutations because they enable single-nucleotide changes without introducing double-strand DNA breaks.
In this study, we developed two distinct base editing approaches to edit point mutations in the LMNA gene associated with cardiac disease. We demonstrated their efficacy using patient-derived cardiomyocytes and humanized mouse models. Our work represents an important step toward the potential clinical correction of cardiomyopathies using gene editing tools.
Abstract
Mutations in the Lamin A (LMNA) gene, which encodes the Lamin A and C proteins, cause severe human diseases collectively known as laminopathies. These conditions are often devastating and lack effective therapies.
In this study, we developed precise base editing (BE) strategies targeting the human LMNA gene variants L35P and R249Q, which cause congenital muscular dystrophy (CMD) and dilated cardiomyopathy with conduction defects (DCM-CD), respectively.
Induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) carrying the R249Q mutation displayed nuclear aberrations, DNA damage, and abnormal Ca2+ transients.
Similarly, L35P iPSC-CMs exhibited abnormal contraction, DNA damage, and reduced Lamin A/C protein expression.
We also generated “humanized” mouse models carrying these pathogenic human mutations. R249Q homozygous mice exhibited cardiac conduction abnormalities, cardiac arrhythmias, and premature death. Mice with the homozygous L35P mutation displayed severe muscle-wasting and reduced lifespan, while heterozygous L35P mice displayed DCM.
We developed an adenine base editing (ABE) approach for correcting the R249Q mutation and a cytosine base editing (CBE) strategy for the L35P variant.
Precise correction of these mutations in iPSC-CMs successfully rescued all of the in vitro abnormalities.
Furthermore, delivery of the BE components using adeno-associated virus prevented the pathological phenotypes and extended longevity of mice carrying the LMNA L35P and the R249Q mutations.
These results demonstrate the efficacy of ABE and CBE in correcting pathogenic LMNA mutations that cause cardiac disease, highlighting BE as a promising therapeutic approach for human laminopathies."
Apparently, there was some very similar work done very recently by researchers mainly from Spain:
Researchers used a technique called base editing to correct a mutation in the lamin A gene. At 8 months old, heart cross sections from treated mice resembled those of normal healthy mice.
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