Myotonic Dystrophy.
What is myotonic dystrophy?
Myotonic dystrophy (DM) is a form of muscular dystrophy that affects muscles and many other organs of the body. DM is a rare muscle disease that affects only 1 in every 8,000 individuals and is divided into two main types depending on the genetic alteration that causes the disease.
What is a rare disease? A rare disease is one that affects a small absolute number of people or a small proportion of the population. In Europe, a disease is considered “rare” if it affects fewer than 1 in 2,000 people. In the United States, it is defined as a disorder or disease affecting fewer than 200,000 people.
Steinert's Myotonic Dystrophy or Myotonic Dystrophy Type 1.
Myotonic dystrophy type 1 (DM1 or Steinert’s disease, OMIM: 160900) is the most common form. DM1 is an autosomal dominant disorder caused by an unstable expansion of cytosine-thymine-guanine [CTG]n trinucleotides located in the 3′ untranslated region of chromosome 19q13.3. Excellent reviews on the genetic origin of myotonic dystrophy type 1 (DM1) and the role of toxic RNA in its pathogenesis are available in the literature.
The [CTG]n expansion responsible for DM1 can vary from 50 to more than 1000 repeats and contributes to a wide range of different phenotypes. According to the International Myotonic Dystrophy Consortium (IDMC) (Neurology, 2000), three different clinical phenotypes are recognized in Steinert’s DM1 depending on the age of onset along with the number of [CTG]n repeats:
- Mild: 50–150 CTG repeats
- Classic (adult-onset) and late-onset forms: 100–1000 CTG repeats
- Congenital: >1000 CTG repeats
What are the symptoms of Steinert's disease.
Clinically, myotonic dystrophy type 1 (DM1) is characterized by progressive muscle atrophy and weakness, cardiomyopathy, insulin resistance, and cataracts, among other features. Myotonic dystrophy DM1 or Steinert’s disease affects women and men equally.
Key advances in Steinert's disease R&D at Myogem.
Currently, there is no cure for patients with Steinert’s disease DM1, only palliative treatments for the symptoms, which means there are multiple unmet medical needs within this group of patients. Management is primarily symptomatic, focused on rehabilitation, psychological support, and regular monitoring via ECG to detect cardiac conduction abnormalities. It is crucial to conduct a screening of all at-risk family members and to provide appropriate genetic counseling, including recommending prenatal diagnosis in pregnancies of affected mothers.
According to data obtained by Myogem Health Company from in vitro and in vivo experiments conducted over the past ten years, the product MyoDM has demonstrated its ability to increase the expression levels of MBNL, both MBNL1 and MBNL2, and their effective amount in the nucleus of human DM1 myoblasts.
The main ingredients of MyoDM are the methylxanthines theobromine and caffeine, and no other food contains the proportion of formulation found in MyoDM. Methylxanthines are secondary plant metabolites derived from purine nucleosides and are present in nearly 100 different plant species (including Theobroma cacao, Coffea arabica, and Camellia sinensis).
MyoDM contains 20mg of caffeine per capsule, meaning that the daily intake of three evenly spaced capsules results in a maximum intake of 60mg. In this regard, MyoDM complies with current legislation on caffeine content in food supplements, for which a maximum daily amount of 80mg is accepted.
Taking a 70kg individual as a reference, taking one capsule of MyoDM (with its 20mg of caffeine) would correspond to an intake of 0.28mg/kg in a 70kg individual. The European Food Safety Authority (EFSA), in its expert reports (“Scientific Opinion on the safety of caffeine,” EFSA Journal 2015;13(5):4102), indicates that in the general healthy population, single doses of caffeine up to 3 mg/kg for a 70kg adult (equivalent to 200mg of caffeine in a single intake) are safe. In general, regular caffeine doses up to 400mg/day are considered safe in adults.
In addition to trials indicating a higher level of MBNL expression with MyoDM intake, a recent clinical study conducted at Donostia University Hospital has confirmed significant health benefits for individuals suffering from DM1.
Is Steinert's Myotonic Dystrophy hereditary?
Myotonic dystrophy is a hereditary disease. It is passed from parents to children through an autosomal dominant pattern, which means that if one parent has the disease, there is a 50% chance that their children will inherit it, as outlined in ‘Epidemiological study of congenital Steinert’s myotonic dystrophy: Dysmorphic characteristics‘.
In the specific case of Steinert’s myotonic dystrophy, it is inherited in an autosomal dominant manner through the mother. This means that if the mother has the disease, there is a high probability that her children will also have it.
Diagnosis of myotonic dystrophy or Steinert's syndrome.
Although Steinert’s disease primarily manifests in the skeletal muscles, the first symptoms may not be muscular, which can delay diagnosis. Therefore, it is essential to conduct a genetic study on all at-risk family members to identify carriers and provide appropriate genetic counseling. Beyond muscle weakness, atrophy, or myotonia, these are some other clinical aspects through which the disease can manifest:
· Cardiac: arrhythmias due to fibrosis of the conduction pathways, which may include first-degree atrioventricular block, sinus bradycardia, and bundle branch block.
· Respiratory: hypoventilation due to diaphragmatic hypotonia and an increased risk of respiratory infections.
· Other: cataracts (common and used as a carrier marker), frontal baldness in men, gonadal atrophy, gastrointestinal alterations such as dysphagia and nonspecific abdominal pain, and metabolic problems such as altered blood glucose levels.
What complementary tests are recommended for the detection or diagnosis of myotonic dystrophy?
· Electrocardiogram (ECG): to detect arrhythmias and other cardiac conduction abnormalities.
· Blood analysis: may reveal elevated muscle CPK levels.
· Genetic DNA analysis: allows for prenatal diagnosis and identification of asymptomatic family members or those with mild symptoms.
· Neurophysiological study: shows a myopathic pattern and is useful for early diagnosis and disease monitoring.
Does Steinert's disease affect life expectancy?
The symptoms of myotonic dystrophy type 1 progress gradually, which can significantly reduce the life expectancy of patients. Some complications associated with the disease include sleep problems such as daytime hypersomnia or excessive daytime sleepiness, cardiovascular difficulties such as cardiomyopathy or arrhythmias, and other symptoms like drooping eyelids, cataracts, early-onset baldness in men, or diabetes.
For all these reasons, the life expectancy of patients with Steinert’s disease can be significantly reduced due to the aforementioned complications. Generally, it does not exceed 55 years in many cases due to the progression of muscle weakness and cardiac problems.
However, the extent of the impact on life expectancy largely depends on the timing of symptom onset. Constant monitoring and symptom management can improve quality of life and potentially extend life expectancy within the limits allowed by the disease.
Figura adaptada de Myotonic Dystrophy Foundation
