Mitochondria are tiny structures in cells that convert the food we eat into the energy our cells need to function.

Mitochondrial disease (or mito for short) is a group of conditions that affect this ability to generate the energy organs require to work properly. There are many different forms of mito and depending on the form, it can disrupt one or more organs and can cause organ failure.

There is no cure for mito. But an IVF procedure called mitochondrial donation now offers hope to families affected by some forms of mito that they can have genetically related children free from mito.

After a law to allow mitochondrial donation in Australia was passed in 2022, scientists are now preparing for a clinical trial to see if mitochondrial donation is safe and works.

What is mitochondrial disease?

There are two types of mitochondrial disease.

One is caused by faulty genes in the nuclear DNA, the DNA we inherit from both our parents and which makes us who we are.

The other is caused by faulty genes in the mitochondria’s own DNA. Mito caused by faulty mitochondrial DNA is passed down through the mother. But the risk of disease is unpredictable, so a mother who is only mildly affected can have a child who develops serious disease symptoms.

Mitochondrial disease is the most common inherited metabolic condition affecting one in 5,000 people.

Some people have mild symptoms that progress slowly, while others have severe symptoms that progress rapidly. Mito can affect any organ, but organs that need a lot of energy such as brain, muscle and heart are more often affected than other organs.

Mito that manifests in childhood often involves multiple organs, progresses rapidly, and has poor outcomes. Of all babies born each year in Australia, around 60 will develop life-threatening mitochondrial disease.

What is mitochondrial donation?

Mitochondrial donation is an experimental IVF-based technique that offers people who carry faulty mitochondrial DNA the potential to have genetically related children without passing on the faulty DNA.

It involves removing the nuclear DNA from the egg of someone who carries faulty mitochondrial DNA and inserting it into a healthy egg donated by someone not affected by mito, which has had its nuclear DNA removed.

The resulting egg has the nuclear DNA of the intending parent and functioning mitochondria from the donor. Sperm is then added and this allows the transmission of both intending parents’ nuclear DNA to the child.

A child born after mitochondrial donation will have genetic material from the three parties involved: nuclear DNA from the intending parents and mitochondrial DNA from the egg donor. As a result the child will likely have a reduced risk of mito, or no risk at all.

This highly technical procedure requires specially trained scientists and sophisticated equipment. It also requires both the person with mito and the egg donor to have hormone injections to stimulate the ovaries to produce multiple eggs. The eggs are then retrieved in an ultrasound-guided surgical procedure.

Mitochondrial donation has been pioneered in the United Kingdom where a handful of babies have been born as a result. To date there have been no reports about whether they are free of mito.

Maeve’s Law

After three years of public consultation The Mitochondrial Donation Law Reform (Maeve’s Law) Bill 2021 was passed in the Australian Senate in 2022, making mitochondrial donation legal in a research and clinical trial setting.

Maeve’s law stipulates strict conditions including that clinics need a special licence to perform mitochondrial donation.

To make sure mitochondrial donation works and is safe before it’s introduced into Australian clinical practice, the law also specifies that initial licences will be issued for pre-clinical and clinical trial research and training.

We’re expecting one such licence to be issued for the mitoHOPE (Healthy Outcomes Pilot and Evaluation) program, which we are part of, to perfect the technique and conduct a clinical trial to make sure mitochondrial donation is safe and effective.

Before starting the trial, a preclinical research and training program will ensure embryologists are trained in “real-life” clinical conditions and existing mitochondrial donation techniques are refined and improved. To do this, many human eggs are needed.

The need for donor eggs

One of the challenges with mitochondrial donation is sourcing eggs. For the preclinical research and training program, frozen eggs can be used, but for the clinical trial “fresh” eggs will be needed.

One possible source of frozen eggs is from people who have stored eggs they don’t intend to use.

A recent study looked at data on the outcomes of eggs stored at a Melbourne clinic from 2012 to 2021. Over the ten-year period, 1,132 eggs from 128 patients were discarded. No eggs were donated to research because the clinics where the eggs were stored did not conduct research requiring donor eggs.

However, research shows that among people with stored eggs, the number one choice for what to do with eggs they don’t need is to donate them to research.

This offers hope that, given the opportunity, those who have eggs stored that they don’t intend to use might be willing to donate them to mitochondrial donation preclinical research.

As for the “fresh” eggs needed in the future clinical trial, this will require individuals to volunteer to have their ovaries stimulated and eggs retrieved to give those people impacted by mito a chance to have a healthy baby. Egg donors may be people who are friends or relatives of those who enter the trial, or it might be people who don’t know someone affected by mito but would like to help them conceive.

At this stage, the aim is to begin enrolling participants in the clinical trial in the next 12 to 18 months. However this may change depending on when the required licences and ethics approvals are granted.

Karin Hammarberg, Senior Research Fellow, Global and Women’s Health, School of Public Health & Preventive Medicine, Monash University; Catherine Mills, Professor of Bioethics, Monash University; Mary Herbert, Professor, Anatomy & Developmental Biology, Monash University, and Molly Johnston, Research fellow, Monash Bioethics Centre, Monash University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Each year, more and more Victorians become sick with a flesh-eating bacteria known as Buruli ulcer. Last year, 363 people presented with the infection, the highest number since 2004.

But it has been unclear exactly how it spreads, until now. New research shows mosquitoes are infected from biting possums that carry the bacteria. Mozzies spread it to humans through their bite.

What is Buruli ulcer?

Buruli ulcer, also known as Bairnsdale ulcer, is a skin infection caused by the bacterium Mycobacterium ulcerans.

It starts off like a small mosquito bite and over many months, slowly develops into an ulcer, with extensive destruction of the underlying tissue.

While often painless initially, the infection can become very serious. If left untreated, the ulcer can continue to enlarge. This is where it gets its “flesh-eating” name.

Thankfully, it’s treatable. A six to eight week course of specific antibiotics is an effective treatment, sometimes supported with surgery to remove the infected tissue.

Where can you catch it?

The World Health Organization considers Buruli ulcer a neglected tropical skin disease. Cases have been reported across 33 countries, primarily in west and central Africa.

However, since the early 2000s, Buruli ulcer has also been increasingly recorded in coastal Victoria, including suburbs around Melbourne and Geelong.

Scientists have long known Australian native possums were partly responsible for its spread, and suspected mosquitoes also played a role in the increase in cases. New research confirms this.

Our efforts to ‘beat Buruli’

Confirming the role of insects in outbreaks of an infectious disease is achieved by building up corroborating, independent evidence.

In this new research, published in Nature Microbiology, the team (including co-authors Tim Stinear, Stacey Lynch and Peter Mee) conducted extensive surveys across a 350 km² area of Victoria.

We collected mosquitoes and analysed the specimens to determine whether they were carrying the pathogen, and links to infected possums and people. It was like contact tracing for mosquitoes.

Molecular testing of the mosquito specimens showed that of the two most abundant mosquito species, only Aedes notoscriptus (a widespread species commonly known as the Australian backyard mosquito) was positive for Mycobacterium ulcerans.

We then used genomic tests to show the bacteria found on these mosquitoes matched the bacteria in possum poo and humans with Buruli ulcer.

We further analysed mosquito specimens that contained blood to show Aedes notoscriptus was feeding on both possums and humans.

To then link everything together, geospatial analysis revealed the areas where human Buruli ulcer cases occur overlap with areas where both mosquitoes and possums that harbour Mycobacterium ulcerans are active.

Stop its spread by stopping mozzies breeding

The mosquito in this study primarily responsible for the bacteria’s spread is Aedes notoscriptus, a mosquito that lays its eggs around water in containers in backyard habitats.

Controlling “backyard” mosquitoes is a critical part of reducing the risk of many global mosquito-borne disease, especially dengue and now Buruli ulcer.

You can reduce places where water collects after rainfall, such as potted plant saucers, blocked gutters and drains, unscreened rainwater tanks, and a wide range of plastic buckets and other containers. These should all be either emptied at least weekly or, better yet, thrown away or placed under cover.

There is a role for insecticides too. While residual insecticides applied to surfaces around the house and garden will reduce mosquito populations, they can also impact other, beneficial, insects. Judicious use of such sprays is recommended. But there are ecological safe insecticides that can be applied to water-filled containers (such as ornamental ponds, fountains, stormwater pits and so on).

Recent research also indicates new mosquito-control approaches that use mosquitoes themselves to spread insecticides may soon be available.

How to protect yourself from bites

The first line of defence will remain personal protection measures against mosquito bites.

Covering up with loose fitted long sleeved shirts, long pants, and covered shoes will provide physical protection from mosquitoes.

Applying topical insect repellent to all exposed areas of skin has been proven to provide safe and effective protection from mosquito bites. Repellents should include diethytolumide (DEET), picaridin or oil of lemon eucalyptus.

While the rise in Buruli ulcer is a significant health concern, so too are many other mosquito-borne diseases. The steps to avoid mosquito bites and exposure to Mycobacteriam ulcerans will also protect against viruses such as Ross River, Barmah Forest, Japanese encephalitis, and Murray Valley encephalitis.

Cameron Webb, Clinical Associate Professor and Principal Hospital Scientist, University of Sydney; Peter Mee, Adjunct Associate Lecturer, School of Applied Systems Biology, La Trobe University; Stacey Lynch, Team Leader- Mammalian infection disease research, CSIRO, and Tim Stinear, Professor of Microbiology, The University of Melbourne

This article is republished from The Conversation under a Creative Commons license. Read the original article.