21. What Treatments are currently available?
Most therapeutic treatments for mitochondrial disease aim to either reduce damage to mitochondria, improve energy generation or remove toxin build up.
Supplements like cofactors (made by the body) or vitamins (from food) can help with this and are often prescribed by clinicians in combination as a ‘cocktail’ tailored to the individual patient.
Although there is still no clinical evidence that these supplements alter the course of the disease, some individuals have reported feeling some benefits. These supplements appear to have few side effects, and so a trial of supplements may be discussed at the mitochondrial clinic review.
Reducing Damage to Mitochondria
Antioxidants can prevent damage to mitochondria by neutralizing highly charged molecules called ‘free radicles’ in the cell.
Coenzyme Q10 (CoQ10, Ubiqinone)
CoQ10 is produced by our bodies but is also found in foods like meat, poultry, nuts and green leafy vegetables. CoQ10 plays a key role in transporting electrons between complexes I, II and III of the mitochondrial respiratory chain. In patients with mitochondrial disease where respiratory chaincomplexes I, II and III are affected, supplementation with coenzyme Q10 is believed to have a therapeutic effect.
In addition, Coenzyme Q10 also has antioxidant properties which could help prevent mitochondrial damage.
This is a synthetic version of CoQ10, but is designed to penetrate the nervous system more easily.
It works in exactly the same way as CoQ10, as a transporter of electrons and as an antioxidant.
Studies of idebenone have suggested some beneficial effects in patients with Leber’s hereditary optic neuropathy (LHON). The National Institute for Health and Care Excellence (NICE) are currently considering reviewing evidence in order to develop a clinical guideline for idebenone in people with LHON.
Riboflavin (Water soluble vitamin B2)
This vitamin is a key building block in Complex I and II, and also helps in stabilizing the mitochondrial membrane. Early studies have shown riboflavin may be helpful in treating mitochondrial diseases where there is complex I involvement, particularly if the complex I deficiency is the result of a mutation in the ACAD9 gene.
Other antioxidants that may be of benefit to mitochondrial patients include selenium, vitamin C, vitamin E, and lipoic acid.
Improving Energy Generation
Creatine is a small molecule that helps supply the body with extra energy during times of high demand.
Creatine is made in the body but can also be found in red meats and fish. The highest concentrations in our bodies are found in tissues with the highest energy demands like muscle and brain.
Some patients have a deficiency of creatine and it has been suggested that a dietary supplement of creatine may benefit this group. Even in those without creatine deficiency, supplementation may have a role in improving muscle strength during activity, although there have not yet been any long term studies undertaken.
Removing Toxin Build up
When a person has mitochondrial disease, their mitochondrial respiratory chain (which is responsible for making energy in the form of ATP) may not be working correctly. This block can lead to a buildup of chemicals in the cells which can be toxic to the body and cause secondary problems.
Sodium Bicarbonate & Dichloroacetate
The most common example of toxin build up in mitochondrial disease is pyruvate, which can accumulate outside the mitochondria if there is a problem in the respiratory chain. Our body then converts this pyruvate into lactic acid. If lactic acid is present at elevated levels for extended periods of time, it can cause direct damage to tissues like the brain and muscle. It is therefore beneficial to ensure that patients with mitochondrial disease should try and minimise the buildup of lactic acid.
In rare situations, individuals with specific types of mitochondrial disease may become critically unwell due to persistently elevated lactate levels. Intravenous hydration is the first line of treatment for such individuals. In emergency situations of profound lactic acidosis not responding to intravenous hydration, sodium bicarbonate and/or dichloroacetate may be considered. It is important to note that risks have been associated with the use of dichloroacetate (DCA). The mitochondrial disease teams can be contacted directly for advice about treatment options as required.
In addition to lactic acid, other metabolites that normally feed into the respiratory chain can buildup in the cells of people with mitochondrial diseases and cause problems.
Carnitine is a natural compound made in the body and can also be found in foods such as red meat, fish, poultry & milk. One of its roles is to clean up these extra metabolites by escorting them out of the cells and into the kidneys for excretion in the urine.
Carnitine deficiency has been observed in some patients with mitochondrial disease so it has been suggested that a dietary supplements might benefit people with a deficiency of L Carnitine.
Thiamine (Vitamin B1)
The use of thiamine has been established in the treatment of some forms of PDH deficiency and Kearns-Sayre syndrome. Benefit from thiamine supplementation has not been demonstrated in a larger study, including people with a wider range of types of mitochondrial diseases.
Treatments, Supportive Therapies & Monitoring
Good treatments exist for many of the associated complications of mitochondrial disease, for example:
- seizures can be managed with anti-epileptic medications or the use of a ketogenic diet under medical supervision in some cases,
- heart failure, cardiomyopathy or arrhythmias can be managed with medications, pacemakers or defibrillators,
- L-Arginine may be beneficial in the management of acute stroke like episodes
- diabetes can be managed through careful diet and medication including insulin if required, as advised by the specialist diabetes team
- droopy eyelids (ptosis) can be alleviated by corrective surgery, and sometimes by props attached to glasses called Lundi Loops which can help to keep eyelids more open
- endocrine dysfunctions can benefit from appropriate hormone replacement,
- folinic acid supplements may be beneficial in patients with Kearns-Sayre syndrome
- hearing loss can be restored or improved with the use of hearing aids, or where the specialist team have recommended cochlear implants,
- although transplantation of single organs is usually not appropriate (as most mitochondrial diseases involve multiple organ systems), there are uncommon circumstances in which specific organ transplantation may be considered. These include liver transplants in patients with some mitochondrial depletion syndromes (with no neurological involvement), heart transplants in some patients with isolated cardiomyopathy, or kidney transplants.
- Stem cell transplants in some MNGIE patients has given promising early results,
The goal of supportive therapy is not to change the underlying mitochondrial disease, but to preserve and maintain strength, mobility, and functioning.
Physiotherapy, occupational, visual, speech and respiratory therapies can all be beneficial to mitochondrial patients.
Although it may not be possible to treat all of the primary causes of mitochondrial diseases, early intervention is likely to improve outcome.
In some cases (particularly in adults) patients may actually be in greater danger from treatable complications than from the mitochondrial disease itself so it is wise to ensure that people living with a mitochondrial disease should make sure their condition is actively monitored.
Regular appointments and monitoring, including physical assessment and blood tests, are recommended. Cardiac investigations, including ECG's, Echo and cardiacMRI, are also recommended, particularly for people whose mitochondrial disease is caused by a change to the mitochondrial DNA. Regular review and monitoring can help to identify changes early, allowing intervention and treatment where possible.
Lifestyle & Exercise
Some individuals with mitochondrial diseases appear more sensitive to physiologic stressors such as minor illness, dehydration, fever, temperature extremes, surgery, anaesthesia, and prolonged fasting or starvation, fatigue and/or stress.
During episodes of increased stress to the body, individuals may become unwell and in some cases may need to be admitted to hospital.
Preventive measures are aimed at avoiding, or reducing the chance of deterioration. These include:
- eating regularly, avoid fasting and intentional weight loss
- staying well hydrated (early administration of oral and/or IV fluids & dextrose during illness)
- correcting lactic acidosis: this often responds to rehydration with intravenous fluids but in some circumstances administration of sodium bicarbonate is required. Dichloroacetate causes nerve damage and is reserved for very severe acidosis unresponsive to sodium bicarbonate and fluids.
- avoiding exposure to pharmacologic mitochondrial toxins (alcohol, cigarettes)
- providing cofactor and/or vitamin therapies.
- protection from infectious diseases.
- managing fatigue and stress