Friday’s morning sessions focused on deepening understanding of the mechanisms underlying diseases of the muscles and nervous system

Among the highlights:

• Spinal muscular atrophy (SMA): Christine DiDonato from Northwestern University presented her work with mice that have a disease mimicking spinal muscular atrophy (SMA) with varying degrees of severity, which is characteristic of human SMA patients. DiDonato’s presentation enhances understanding of how motor neurons (muscle-controlling nerve cells) and other types of cells are affected by varying amounts of the SMN protein, which is deficient in SMA. The more SMN one has, the milder the disease course is – in mice and in human patients. Developing and using these mice with varying levels of disease severity and varying amounts of SMN protein is important when drugs are being designed for patients  with (most severe), type 2  (intermediate) and type 3 (least severe) SMA.
• ALS (amyotrophic lateral sclerosis): Justin Ichida from the University of Southern California described his lab’s experiments to shed light on the mechanisms by which expanded DNA in the C9ORF72 gene leads to amyotrophic lateral sclerosis (ALS). This C9ORF72 expansion is the most common genetic form of ALS identified to date, but it has so far been unclear just how it causes the disease. Using cells from ALS patients with the C9ORF72 gene mutation, Ichida’s group found that at least some of the normal functions of the C9ORF72 protein are lost, leading to the degeneration of cells. Previously, it was widely believed that the C9ORF72 abnormalities seen in ALS conferred additional and toxic properties to the C9ORF72 protein or the genetic instructions for it. Ichida said there may be some of this “toxic gain” going on, but he believes that most of the problem in ALS is the loss of the protein’s usual functions. The findings suggest that restoring C9ORF72 could become a potential therapy for C9-related ALS.
• Congenital muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD): M. Chiara Manzini from George Washington University and Kevin Campbell from the University of Iowa both presented findings related to a mechanism that underlies many types of congenital muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD) – namely, insufficient glycosylation (coating with sugar molecules) of a muscle-fiber membrane protein known as dystroglycan. Understanding this process more thoroughly allows for more points at which scientists can intervene to correct it.
• Facioscapulohumeral muscular dystrophy (FSHD): Scott Harper and Carlee Giesige, both from Nationwide Children’s Hospital in Columbus, Ohio, each gave talks on how production of a protein known as DUX4 in muscle tissue long after early development leads to the disease known as facioscapulohumeral muscular dystrophy (FSHD). DUX4 production is normally turned off early in life, but in people with FSHD, it stays turned on. Understanding exactly what this protein does and how to examine its effects in mice (which do not make a protein exactly like human DUX4) is crucial to developing FSHD therapies.