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.

Menopause is a natural biological process that marks the end of a woman’s reproductive years, typically between 45 and 55. As women approach or experience menopause, common “change of life” concerns include hot flushes, sweats and mood swings, brain fog and fatigue.

But many women may not be aware of the long-term effects of menopause on the heart and blood vessels that make up the cardiovascular system. Heart disease accounts for 35% of deaths in women each year – more than all cancers combined.

What should women – and their doctors – know about these risks?

Hormones protect hearts – until they don’t

As early as 1976, the Framingham Heart Study reported more than twice the rates of cardiovascular events in postmenopausal than pre-menopausal women of the same age. Early menopause (younger than age 40) also increases heart risk.

Before menopause, women tend to be protected by their circulating hormones: oestrogen, to a lesser extent progesterone and low levels of testosterone.

These sex hormones help to relax and dilate blood vessels, reduce inflammation and improve lipid (cholesterol) levels. From the mid-40s, a decline in these hormone levels can contribute to unfavourable changes in cholesterol levels, blood pressure and weight gain – all risk factors for heart disease.

4 ways hormone changes impact heart risk

1. Dyslipidaemia– Menopause often involves atherogenic changes – an unhealthy imbalance of lipids in the blood, with higher levels of total cholesterol, triglycerides, and low-density lipoprotein (LDL-C), dubbed the “bad” cholesterol. There are also reduced levels of high-density lipoprotein (HDL-C) – the “good” cholesterol that helps remove LDL-C from blood. These changes are a major risk factor for heart attack or stroke.

2. Hypertension – Declines in oestrogen and progesterone levels during menopause contribute to narrowing of the large blood vessels on the heart’s surface, arterial stiffness and raise blood pressure.

3. Weight gain – Females are born with one to two million eggs, which develop in follicles. By the time they stop ovulating in midlife, fewer than 1,000 remain. This depletion progressively changes fat distribution and storage, from the hips to the waist and abdomen. Increased waist circumference (greater than 80–88 cm) has been reported to contribute to heart risk – though it is not the only factor to consider.

4. Comorbidities – Changes in body composition, sex hormone decline, increased food consumption, weight gain and sedentary lifestyles impair the body’s ability to effectively use insulin. This increases the risk of developing metabolic syndromes such as type 2 diabetes.

While risk factors apply to both genders, hypertension, smoking, obesity and type 2 diabetes confer a greater relative risk for heart disease in women.

So, what can women do?

Every woman has a different level of baseline cardiovascular and metabolic risk pre-menopause. This is based on their genetics and family history, diet, and lifestyle. But all women can reduce their post-menopause heart risk with:

• regular moderate intensity exercise such as brisk walking, pushing a lawn mower, riding a bike or water aerobics for 30 minutes, four or five times every week
• a healthy heart diet with smaller portion sizes (try using a smaller plate or bowl) and more low-calorie, nutrient-rich foods such as vegetables, fruit and whole grains
• plant sterols (unrefined vegetable oil spreads, nuts, seeds and grains) each day. A review of 14 clinical trials found plant sterols, at doses of at least 2 grams a day, produced an average reduction in serum LDL-C (bad cholesterol) of about 9–14%. This could reduce the risk of heart disease by 25% in two years
• less unhealthy (saturated or trans) fats and more low-fat protein sources (lean meat, poultry, fish – especially oily fish high in omega-3 fatty acids), legumes and low-fat dairy
• less high-calorie, high-sodium foods such as processed or fast foods
• a reduction or cessation of smoking (nicotine or cannabis) and alcohol
• weight-gain management or prevention.

What about hormone therapy medications?

Hormone therapy remains the most effective means of managing hot flushes and night sweats and is beneficial for slowing the loss of bone mineral density.

The decision to recommend oestrogen alone or a combination of oestrogen plus progesterone hormone therapy depends on whether a woman has had a hysterectomy or not. The choice also depends on whether the hormone therapy benefit outweighs the woman’s disease risks. Where symptoms are bothersome, hormone therapy has favourable or neutral effects on coronary heart disease risk and medication risks are low for healthy women younger than 60 or within ten years of menopause.

Depending on the level of stroke or heart risk and the response to lifestyle strategies, some women may also require medication management to control high blood pressure or elevated cholesterol levels. Up until the early 2000s, women were underrepresented in most outcome trials with lipid-lowering medicines.

The Cholesterol Treatment Trialists’ Collaboration analysed 27 clinical trials of statins (medications commonly prescribed to lower cholesterol) with a total of 174,000 participants, of whom 27% were women. Statins were about as effective in women and men who had similar risk of heart disease in preventing events such as stroke and heart attack.

Every woman approaching menopause should ask their GP for a 20-minute Heart Health Check to help better understand their risk of a heart attack or stroke and get tailored strategies to reduce it.

Treasure McGuire, Assistant Director of Pharmacy, Mater Health SEQ in conjoint appointment as Associate Professor of Pharmacology, Bond University and as Associate Professor (Clinical), The University of Queensland

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