In many cases, therapies for patients with rare disease are first tested or developed in either 2D cell cultures or in animal models, such as fruit flies, mice, or zebrafish. Unfortunately, promising results in animal models do not always translate to promising results for patients. So how can researchers create beneficial and targeted therapies that actually address patient needs? According to Medical XPress, IBEC researchers have been working to address this issue in relation to myotonic dystrophy. Using bioengineering and patient cells, researchers created a 3D myotonic dystrophy model. Ultimately, this model will help to develop more targeted, effective, and personalized treatment options. See how the 3D model was created in Biofabrication.

3D Modeling

To begin, researchers used reprogrammed fibroblasts, which became myoblasts, sourced from patient skin. According to the Biology Online Dictionary, myoblasts are:

the embryonic precursors of myocytes (also called muscle cells). Myoblasts differentiate into muscle cells through a process called myogenesis [when] the myoblasts fuse into multi-nucleated myotubes, which later become the muscle fibers.

Next, the researchers inserted these engineered myoblasts into a gel-cellulose matrix. Once inside of the matrix, the entire shape was reorganized into elongated rectangles to make it duplicate muscle fibers and then incubated. Ultimately, researchers wanted to give the myoblasts the ability to continually grow and develop. This was successful, with cells coming together to create muscle fibers.

Then researchers evaluated how well the 3D model could offer insights into potential treatments. To begin, researchers treated the muscle fibers with AntagomiR-23b, normally administered subcutaneously. After treatment, the muscle fibers became stronger. AntagomiR-23b reduced symptoms associated with myotonic dystrophy, such as myotonia, or the inability to relax voluntary muscles. Ultimately, the ability to directly see treatment response highlights how the 3D model can be used in drug development and testing.

Myotonic Dystrophy

There are two major forms of myotonic dystrophy, a rare and progressive disease resulting in muscle degeneration. DPMK gene mutations typically cause type 1, the more severe form. In this form, muscle weakness often affects the hands, neck, face, and lower legs. Alternately, ZNF9 mutations cause type 2, whose symptoms are often milder. In this form, muscle weakness affects the elbows, hips, neck, and shoulders. Myotonic dystrophy is considered the most common form of muscular dystrophy in adulthood. Symptoms include:

• Voluntary muscle weakness
• Prolonged muscle contractions
• Cataracts
• Type 2 diabetes
• Heart, lung, and gastrointestinal tract muscle weakness
  • Note: Altogether, symptoms associated with these muscle weaknesses include difficulty breathing and swallowing, an abnormal heart rhythm, constipation, and gallstones.
• Difficulties and complications in pregnancy and labor
• Infertility (in males)
• Developmental and cognitive delays
• Speech, hearing, and vision difficulties
• Clubfoot

Learn more about myotonic dystrophy.