disease in focus
The more we can understand mitochondrial diseases, the better equipped we are to develop transformative medicines for patients living with these rare disorders.
what are mitochondria?
Within all cells of the human body, mitochondria act as a powerhouse – collectively producing energy that is essential for life. When these mitochondria are defective, the result can take the form of a wide range of serious and debilitating illnesses, caused by a multitude of cellular consequences – important ones being disturbed redox, lipid peroxidation and inflammation.
what is mitochondrial disease
Mitochondrial diseases are rare diseases belonging to the most frequently encountered inborn errors of metabolism, causing a progressive burden for patients, their families and society. They comprise a group of ~300 neuro-metabolic genetic disorders occurring shortly after birth or later in life, all affecting the cell’s energy generators – mitochondria. In mitochondrial diseases, these generators do not work properly, leading to decreased energy production and leakage of molecules that are toxic for cells and tissues, ultimately causing cell death. As mitochondria are present in almost all cells of the body, malfunctioning leads to multi-organ failure. Symptoms caused by mitochondrial dysfunction in e.g., the brain, retina and skeletal muscle include cognitive decline, epilepsy, strokes, visual loss, movement disorders and muscle weakness. Sadly, there is still no disease-modifying treatment for these multi-system mitochondrial diseases that can halt or even reverse the severe progression of these diseases, which are eventually fatal.
understanding mitochondrial disease
Mitochondrial diseases are complex rare diseases, often overlooked or misdiagnosed because of the wide range and varying severity of symptoms.
In this section, we aim to explain some of the specific mitochondrial syndromes and the symptoms that can cause a significant burden for those living with mitochondrial disease.
Maternally inherited diabetes and deafness
Estimated to affect more than 400 million people around the world, diabetes is one of the most common chronic disorders, with a range of different types – including a mitochondrial disease that manifests as diabetes. Maternally inherited diabetes and deafness, or MIDD, was identified as a specific condition in the early 1990s, after a team of scientists examined reports suggesting an increased incidence of some forms of diabetes being transmitted from mother to child.
Mitochondrial disease heterogeneity
Mitochondrial diseases are a clinically, biochemically and genetically heterogeneous group of disorders. Signs, symptoms and the organs involved can differ from one person to another, making the diagnosis of mitochondrial diseases and the search for potential therapies complex. Here we outline the heterogeneity surrounding mitochondrial diseases and explore some of the challenges biopharma companies active in this field, including Khondrion, face in developing much needed treatments for patients.
Simple functions such as blinking and breathing are actions that we take for granted. However, for those living with Leigh disease, these normally subconscious body functions can become difficult or even impossible to execute at all. First described in the 1950s by Denis Leigh, a British neuropsychiatrist, Leigh disease is a rare inborn error of metabolism, importantly touching the brain, that affects approximately 1 in 40,000 newborns, with quickly progressing symptoms frequently starting in the first year of life.
Cognition and mitochondrial disease
Cognition is an important function of the brain so we can gain knowledge and understanding. These mental processes include thinking, knowing, remembering, judging, planning, understanding and responding to information and problem-solving. They are vital for our everyday functions – whether that’s getting ready for work, remembering where we left our house keys, reminiscing about times from our past or planning a holiday in the future.
Classic MELAS syndrome (Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes), MIDD (maternally inherited diabetes mellitus and deafness) and Mixed Phenotypes all belong to a clinical spectrum of mitochondrial diseases most frequently caused by a mutation, the m.3243A>G mutation, in the MT-TL1 gene in the mitochondrial DNA (mtDNA). Most DNA, called nuclear DNA, is situated in chromosomes within the nucleus of a cell. Mitochondria however, which are found within all cells of the human body, except red blood cells, and are responsible for producing energy necessary for life, also contain small copies of their own DNA known as mitochondrial DNA. In this first of a series of forthcoming mitochondrial disease spotlights we focus on classic MELAS syndrome.
Movement disorders in children with primary mitochondrial disease
Movement, the act or process of moving, the change of place or position or posture, is a complex process under the control of many different parts of the central nervous system including the brain (frontal cortex, basal ganglia, cerebellum) and spinal cord. As brain involvement is common in all ages of primary mitochondrial disease, many patients with mitochondrial disease encounter movement difficulties, described in medical literature as ‘movement disorders’. Here, we briefly touch upon the movement disorders in children with mitochondrial disease, which have a huge impact on quality of life.