Treatment of a rare genetic condition in the kid using the mother's mitochondria

 One of the kids in the tiny study who received treatment was able to get up on her own after only a few weeks.

On January 7, 2023, by Kristin Houser

First-ever patient testing of a novel treatment that leverages a mother's healthy mitochondria to treat a child's uncommon genetic condition provides cause for optimism.

The difficulty: Your body's cells each contain hundreds to thousands of microscopic structures known as mitochondria. The majority of the energy required by our cells to function is produced by these structures and is stored in molecules known as adenosine triphosphates (ATPs).

Serious health issues can arise throughout the body as a result of mtDNA mutations.

While the majority of your body's DNA is stored in your cells' nuclei, your mitochondria also contain DNA. Unlike nuclear DNA, which we inherit from both parents, this mitochondrial DNA (mtDNA) is inherited exclusively from your mother.

Despite the fact that mtDNA only has 37 genes (compared to nuclear DNA's 20,000+ genes), the significance of mitochondria to cellular function makes mtDNA alterations dangerous for the organism as a whole.

Mitochondrial augmentation therapy is a promising new treatment for mtDNA problems being developed by Israel-based biotech startup Minovia Therapeutics (MAT).

The Minovia scientists were aware of the ability of isolated mitochondria to penetrate neighbouring cells as a result of prior study. They got the idea from that to add donor-derived healthy mitochondria to patient-derived stem cells from bone marrow who had an mtDNA issue.

It was hoped that the mother's healthy mitochondria would enter the stem cells of her kid.

This healthy mitochondria might be obtained from the patient's own mother in the case of individuals with non-inherited mtDNA diseases brought on by completely new mutations. The mitochondria might be extracted from donated placenta tissue if a mother was unable to give or if the patient got their mtDNA condition from their mother.

In either case, it was hoped that the stem cells would absorb the healthy mitochondria and subsequently reintroduce them into the patient's circulation. The patient may have more healthy mitochondria as a result, which should assist alleviate their disease.

The programme: In December 2022, Minovia revealed that through a compassionate use programme, it had used MAT to treat six young patients with non-inherited mitochondrial disorders. This programme allowed these patients access to novel therapies that had not yet received FDA approval.

Pearson syndrome, which is frequently deadly in infancy and can result in weakness, tiredness, hyperglycemia, and failure to thrive, was present in four of the kids. The other two have Kearns-Sayre syndrome, which has been related to major health concerns like weakness, cardiac troubles, decreased cognition, and others.

"We did find significant improvements in virtually every child's quality of life,"

The patients' blood cells had a median of 30% more complete mtDNA than at baseline one year following therapy. Additionally, the cells created more ATP; before therapy, the children's median ATP production was 62% that of their mothers', but after treatment, it was up to 84%.

Other patients might see the patients' progress as well. A few weeks following the therapy, a girl who couldn't sit up at first was able to stand. A youngster who was completely unable to walk before therapy was able to walk 10 metres a year later.

We did detect significant increases in virtually all of these children's quality of life, but these are very soft indicators that are difficult to report, Elad Jacoby, a paediatric haematologist who conducted the study, told STAT.

Looking forward Although it's too soon to say for sure how effective MAT may be, none of the children who took part in the compassionate use study experienced any severe adverse effects as a result of the therapy. This suggests that MAT is safe.

The organisation will require larger trials with control groups to make that determination. According to the researchers' article, enrolling younger patients with less severe illness may also be advantageous for assessing the therapy's genuine effectiveness.

Even then, measuring efficacy will be challenging given the rarity of these disorders and the scant knowledge we have of how symptoms develop.

Even so, the treatment's evident effects on the kids in the modest programme are heartening, and MAT may prove to be a game-changer for people with these uncommon but critical diseases if it succeeds in the studies that are currently planned.