Friday’s afternoon sessions focused on laboratory studies in animal and cell models of neuromuscular diseases. These kinds of studies are necessary before treatments can be tested in humans.

Among the highlights:

• Spinal muscular atrophy (SMA): Brian Kaspar from Nationwide Children’s Hospital in Columbus, Ohio, presented experiments from his lab to develop gene transfer therapy for spinal muscular atrophy (SMA) in which he and his colleagues utilized pigs with an SMA-like disorder caused by diminished SMN protein. When the pigs were treated with SMN gene transfer very early in life, disease symptoms did not develop. When they received SMN gene transfer later on, after weakness had developed, the treatment stopped the progression of the disease but did not restore lost strength. SMN gene transfer is now being tested in clinical trials in patients with SMA.
• ALS (amyotrophic lateral sclerosis): Brian Kaspar from Nationwide Children’s Hospital in Columbus, Ohio, presented his group’s findings on counteracting abnormal SOD1 protein, a known cause of amyotrophic lateral sclerosis (ALS), in mice with SOD1 gene mutations and an ALS-like disease. The investigators tested a therapy involving transfer of a gene for a “short hairpin RNA,” a type of compound that can reduce protein production. The hairpin RNA was designed to reduce production of toxic SOD1 protein resulting from either of two SOD1 gene mutations. In mice with both types of SOD1 abnormalities, the strategy was effective, and mouse survival was prolonged. The findings suggest that this type of SOD1-countering strategy could be an avenue for treating SOD1-related ALS.
• ALS: David Beers from Houston Methodist Neurological Institute discussed his group’s findings about regulatory T cells (“Tregs”) produced by the immune system in people with ALS. In earlier studies, these cells have been found to protect nerve cells in ALS patients during the early phase of the disease, after which they fail to do so. It’s thought that they prolong nerve-cell survival in ALS through their ability to regulate (suppress) an immune response that attacks nerve cells during the disease process. Beers and his colleagues found that Tregs taken from ALS patients were less able to suppress T cells that mount an immune response than were Tregs taken from healthy subjects. However, additional experiments conducted on the patients’ Tregs in the lab showed that their suppressive ability can be restored, suggesting a possible therapeutic avenue for ALS.
• ALS: Cathleen Lutz from the Jackson Laboratory in Bar Harbor, Maine, discussed her team’s attempt to create mouse models of ALS caused by abnormalities in the C9ORF72 gene – the most common genetic cause of ALS identified to date. Interestingly, the mice did not develop symptoms of ALS, a phenomenon that Lutz says could be due to differences between mice and humans or could be because mice don’t live long enough to develop a C9ORF72-related disease. She says the mice may still be useful for various experiments, such as those investigating strategies to reduce abnormal C9ORF72 protein or genetic instructions for this protein.
• Congenital muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD): Rita Perlingeiro from the University of Minnesota presented her lab’s experiments in mice carrying mutations in the FKRP gene. These mutations cause a deficiency of the FKRP protein, a problem that can lead to either congenital muscular dystrophy (CMD) or limb-girdle muscular dystrophy (LGMD) in humans. The investigators took early-stage muscle cells from patients with FKRP mutations, corrected the mutations (in lab dishes outside the body), and then injected the corrected cells intravenously into the mice with FKRP mutations. The corrected cells had a beneficial effect on respiratory function in the mice, suggesting that this type of therapy could have promise for FKRP-related CMD or LGMD.