Therapeutic Approaches to Genetic Neuromuscular Diseases

The neuromuscular world is an exciting place to be right now. Since the time I trained as a resident and fellow, there has been a sea change in how we diagnose many of our patients as genetic testing has become an increasingly available and detailed tool. This, in turn, is leading to a new era in therapeutic approaches; technology that seemed like science fiction only a few years ago is already being used in the clinic. Indeed, for monogenic diseases, it feels as if the “dominoes are beginning to fall,” slowly now, but with rapidly increasing speed.

Dr. Defne Amado and Ashley Robbins kick off this topic with an overview of the scientific approaches being used to target genetic diseases in the neuromuscular world. Their review, The Emerging Landscape of Targeted Therapeutics for Genetic Neuromuscular Disorders, is a fascinating read with broader applications beyond the neuromuscular domain.

Next, as neuromuscular neurologists like to do, we will march down the neuraxis starting with the motor neuron, traveling through the peripheral nerve and on to the muscle, highlighting conditions that have already been targeted or are in the process of being addressed.

Beginning in the motor neuron, Drs. Mark Garret and Suma Babu along with colleagues Kush Mehta and Jin Yun Chen, take on the Herculean topic of amyotrophic lateral sclerosis (ALS) in Rise of the Genomic Medicine Era in ALS. Although ALS is most commonly thought of as a sporadic disease, there is a significant minority of individuals who have genetically mediated disease and an additional number of patients with known genetic risk factors. Perhaps the most fascinating aspect of targeted medicine in ALS is how we may be able to use strategies born from treating genetic disorders to address the majority of the population with sporadic disease.

The motor neuron is the site of one of the few trials in neurology that required early termination for success. Dr. Perry Shieh takes us through the beginning of the continually evolving story of the treatment of spinal muscular atrophy in Spinal Muscular Atrophy is Now a Treatable Genetic Condition.

There are a few specific conditions within the large group of inherited neuropathies that have been addressed in a targeted way. In their article Inherited Neuropathies: Giant Axonal Neuropathy, Charcot-Marie-Tooth, and Hereditary Transthyretin Amyloidosis, Drs. Taha Qarni and Chafic Karam discuss the clinical and experimental approaches for these 3 conditions.

As a category, muscle disease is the most heterogeneous of all neuromuscular conditions. Addressing muscle diseases that can present in childhood or adulthood, Drs. Sam Carrell and Colin Quinn review RNA therapeutic approaches for 2 common muscle disorders in Therapeutic Approaches to Neuromuscular Repeat Disorders: Facioscapulohumeral Muscular Dystrophy and Myotonic Dystrophy Type 1. On the heels of the recent accelerated approval of gene therapy for a limited population of boys with Duchenne muscular dystrophy, Drs. Ryan Cappa and John Brandsema review treatments for Dystrophinopathies and the Limb Girdle Muscular Dystrophies.

As a neuromuscular neurologist, I find it invigorating to be part of a dramatically changing therapeutic landscape. It is both humbling and exciting to note that, should this issue be rewritten 5 years from now, it will no doubt look completely different.