Scientists Create First Human Model of Leigh Syndrome

Leigh syndrome is a rare mitochondrial disease that is not yet well understood by medical professionals. When this lack of comprehension exists, it is impossible to create treatments or improve care for patients. A large issue that scientists encountered was the difficulty that came with creating a disease model. They could not successfully replicate Leigh syndrome in animal models, rendering them unable to further study the condition. Luckily, scientists from University Hospital Duesseldorf, Germany and Berlin Institute for Medical Systems Biology (BIMSB) of the Max Delbrueck Center for Molecular Medicine (MDC) were able to create a human model of the disease.

About Leigh Syndrome

Leigh syndrome is a neurological condition that typically sees onset during infancy, although some do not experience symptoms until adulthood. Caused by an alteration in one of 75 possible genes, this syndrome is characterized by the deterioration of motor and mental abilities. Symptoms include:

  • Failure to thrive
  • Vomiting, diarrhea
  • Trouble swallowing
  • Weak muscle tone
  • Ataxia
  • Dystonia
  • Rapid eye movements
  • Lactate buildup
  • Respiratory issues
  • Rapid eye movements
  • Paralysis of the muscles that move the eyes
  • Hypertrophic cardiomyopathy
  • Death of the nerves that transfer information from the eyes to the brain

The mutations that cause these symptoms can be inherited in a number of patterns, simply due to the sheer amount of possible genes. Inheritance in an autosomal recessive pattern or mitochondrial pattern is the most common. In terms of treatment, there is no cure. Doctors often utilize thiamine or thiamine derivatives, and they suggest a diet that is low in carbs and high in fat. Both methods are meant to slow disease progression.

A Human Model of Leigh Syndrome

Scientists had been spending a lot of time and effort to create an animal version of Leigh syndrome, specifically with a mutated SURF1 gene. This gene is one of the most common causes of Leigh syndrome.

While their efforts to create an animal model failed, a recent study published in Nature Communications states that they have succeeded in creating a human model of the disease. A team of researchers from the University Hospital Duesseldorf, Germany and the Berlin Institute for Medical Systems Biology (BIMSB) of the Max Delbrueck Center for Molecular Medicine (MDC) worked together on this model.

They utilized cellular reprogramming technology, which is able to transform skin cells into stem cells. These stem cells are able to create neurons. After this, CRISPR/Cas9 was used to take the mutation out of a Leigh syndrome patient’s cells and insert it into a control cell. Once this was done, researchers were able to study the disease as much as they liked. They grew more cells and eventually created brain organoids.

Through these cellular models, the team noticed that an energy deficit may be the reason behind any neuronal defects. When there is a lack of energy, neuronal branching cannot occur at a normal level, and the brain is unable to develop normally. Further research revealed that this problem could be fixed through SURF1 gene replacement therapy or Bezafibrate to heighten the output of energy from progenitor cells.

Looking Forward

These discoveries are very important to the understanding of Leigh syndrome. Now, medical professionals are able to research the condition more easily, which will hopefully lead to better treatment options and even a cure for Leigh syndrome.

Find the source article here.

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