Study of the Week: A new Approach to Treat Mitochondrial Disease

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

 

This week’s study is…

Mitochondrial augmentation of hematopoietic stem cells in children with single large-scale mitochondrial DNA deletion syndromes

We previously published about this research in a story titled “Mitochondrial Transplants from Mothers: A Controversial idea Evolves into a Potential Remedy for Mitochondrial Disease” which can be found here. The study was originally published in the academic journal Science Translational Medicine. You can read the full text of the study here

 

What Happened?

Mitochondrial diseases impact a very important cellular organelle called mitochondria. This organelle, believed to have originated billions of years ago as a relationship between a bacteria and an archaeon, is found in the vast majority of cells in the human body and is responsible for generating a cell’s energy. It should go without saying that when these organelles don’t function correctly, it can lead to some disastrous health problems. 

One form of mitochondrial disease is called mitochondrial DNA deletion disorder (SLSMD), in which a section of the mitochondrial DNA disappears suddenly between generations. There is no cure, occurs in the second decade of life, and typically leads to an early death. However, researchers have been working on an approach that utilizes the ability of mitochondria to transmit to different cellular life forms. The approach is called mitochondrial transplantation, or mitochondrial augmentation therapy.

Healthy mitochondria from the patients’ mothers are transplanted into their stem cells. The approach follows evidence from a 2009 study involving rabbits which found that mitochondrial transplant could help repair heart damage. In this study, six children living with SLSMD underwent the procedure. Almost all of the patients showed signs of improvement with the treatment. For instance, one girl that was bedridden was able to stand up on her own. A boy, aged six, arrived for treatment being pushed around in a stroller; after treatment, he was able to stay awake long enough to eat and gain weight and could run around on his own. The scientists also found that the procedure was generally well tolerated. 

The first child in this group was first treated in 2017. A larger scale clinical trial is being planned to further evaluate the mitochondrial transplant approach and is expected to begin later in 2023. If the trial is a success, this treatment could potentially be used in a wide range of diseases linked to damage of the mitochondria. The researchers documented improved ratios of mitochondrial DNA to deleted DNA, an increase in the number of mitochondrial DNA molecules, and an improved ability of the cells to generate energy. 

About Mitochondrial Diseases

Mitochondrial diseases are a group of genetic disorders that cause the mitochondria not to function properly. The mitochondria are an essential organelle that is found in most types of cells in the body, with red blood cells being the only exception. They are responsible for generating energy for the cell. Mitochondrial diseases are usually caused by mutations of the mitochondrial DNA or the nuclear DNA. Symptoms tend to be the worst when the issue affects cells that use a lot of energy, such as the muscles or parts of the brain. These symptoms affect many aspects of bodily function and include poor growth, poor muscle coordination, dementia, neurological issues, muscle weakness, breathing disorders, vision problems, digestive disorders, hearing problems, disease of the kidney, liver, and heart, and learning disabilities. Treatment options are limited in number and in their effectiveness. To learn more about mitochondrial diseases, click here.

Why Does it Matter?

Overall, there hasn’t been a lot of real progress in the treatment of single large-scale mitochondrial DNA deletion syndromes (SLSMDs), or other forms of mitochondrial disease for that matter.

“These children are extremely weak compared to their peers.” – Elad Jacoby, pediatric hematologist, Sheba Medical Center

While these findings are still very preliminary, they are a strong basis for continued study in the form of the upcoming clinical trial. The findings of this trial could be very important for the mitochondrial disease patient community:

“This is a good first study to show that mitochondrial transplantation is safe in patients with these gene deletion disorders.” – James McCully, researcher, Harvard Medical School

McCully’s research team also recently published findings from a separate study using mitochondrial transplantation. The approach was used on infants born with congenital heart abnormalities. The treatment boosted energy production and metabolism and 80 percent of patients treated were able to breathe independently, versus just 30 percent who were treated with standard of care. 

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