Spinal muscular atrophy is a debilitating disease that causes weakness and wasting of the muscles. The disease ranges in severity with patients experiencing different symptoms, from the inability to sit up and stand, to trouble walking. In its severest form, the disease results in difficulty breathing and leads to death. Spinal muscular atrophy is caused by a genetic mutation that triggers the loss of spinal cord motor neurons, neurons that help control the body’s movements. As the neurons deteriorate, so does one’s ability to control their own movement. The molecular mechanism underlying neurodegeneration in Spinal muscular atrophy is unknown.
Now, a study from researchers at Texas Tech University Health Sciences Center El Paso (TTUHSC El Paso) has identified the specific enzyme, JNK3, required for neuron degeneration in spinal muscular atrophy and found that suppressing this enzyme’s activity markedly reduces the disease’s severity. The team state that they have identified the enzyme JNK3 as a therapeutic target to treat the symptoms of spinal muscular atrophy. The study is published in the journal Human Molecular Genetics.
Previous studies show that spinal muscular atrophy research has focused on targeting the genetic mutation, namely Survival Motor Neuron 1 (SMN1), to prevent degeneration of spinal motor neurons. However, this strategy hasn’t been successful due to the challenges associated with gene therapy. The current study identifies a target, JNK3, that’s independent of the genetic mutation of spinal muscular atrophy for novel therapeutic development.
The current study shows mice with spinal muscular atrophy saw great improvement when the JNK3 enzyme was genetically inhibited to eliminate its activity. Results show less muscle degeneration, more muscle growth and better muscle strength, and improvement in overall movement. Data findings show a four-fold reduction in initial mortality period and a two-fold increase in total lifespan of mice.
The lab state that inhibiting JNK3 in mice prevented the loss of motor neurons, which is particularly important to prevent progression of disease. They go on to hypothesize that patients with spinal muscular atrophy could also see improvement if treated with a drug that suppresses the activity of JNK3.
The team surmise that JNK3 represents a promising new avenue of research for clinical advances in developing a treatment. For the future, the researchers now plan to test pharmacological compounds that can inhibit JNK3 in mice to slow the progression of the disease and reduce the overall burden of this illness in patients; they’ve also decided to patent their idea of using a JNK3 inhibitor to treat spinal muscular atrophy.