Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disease characterized by motor neuron loss and muscle atrophy and weakness. The disease is caused by deletion or mutational inactivation of the SMN1 gene that encodes survival of motor neuron (SMN) protein, critical to motor neuron health and survival. The disease typically presents in early infancy and is currently the leading genetic cause of death of infants and toddlers. Presently there is no cure for SMA.
The lack of treatment for SMA is something that the New York-based SMA Foundation is working to change; here the aim is to speed up the development of a pioneering treatment for the disease.
Dione Kobayashi is a Director at the SMA Foundation. Her role there is to oversee the development of biomarker tools and protocols for SMA as well as managing the Foundation’s in vivo drug testing pipeline. She tells me it was the apparent tangibility of an SMA cure that drew her to the study of this disease…
“I have been involved in neurodegeneration research for a number of years. My doctoral studies at the University of Edinburgh, and much of my prior industry work, were on Alzheimer’s and Parkinson’s disease. These are well-known disorders that are generally not caused by single genetic mutations and there are still many unknowns as to how people get these diseases – unlike SMA.”
“I learned about SMA from a former colleague of mine after they joined the SMA Foundation. As I discovered more about the unique genetics of SMA – which is caused by the loss of a single gene SMN1 – I was deeply intrigued because it seemed that it was conceptually ‘curable’. This concept is possible due to the presence of a nearly identical ‘backup’ gene called SMN2 that could be targeted for upregulation. Working on SMA thus creates an ideal situation, where a scientist is engaged on an elegant problem that appears to have a biologically built-in rescue system.” The potential to manipulate this natural, but currently flawed rescue system (a lot of SMN2 is expressed as the unstable SMNΔ7) she says, “Will help to find treatments and save and improve the lives of thousands of children.”
In August last year, Kobayashi and her colleagues published a paper describing the development of a sandwich ELISA kit for the detection of SMN protein in blood – specifically, in samples of peripheral blood mononuclear cells (PBMCs).
This assay is a significant advancement in SMA research due to the critical lack of a biomarker-based method to assess potential SMA therapies. Despite several prospective treatments for SMA being under evaluation at present, their efficacy is difficult to assess with current diagnostic tools.
Though several other groups have developed useful laboratory assays for SMN, Kobayashi explains why the SMA Foundation-developed ELISA kit has an advantage in the clinical area:
“This particular ELISA has gone through quality control processes in an effort to ensure that each off-the-shelf kit can produce robust and reproducible results. Also, the assay has been shown to be useful for a number of different in vitro and in vivo applications with both human and mouse cells and tissues.”
Essentially, the kit has general translational applicability to both preclinical and clinical research. In other words it could speed-up the “bench to bedside” journey of any prospective treatments from lab to clinic. This, as mentioned previously, is the main goal of the SMA Foundation as Kobayashi explains:
“Our mission at the SMA Foundation is to accelerate the development of therapies for SMA. SMA causes devastating weakness in patients and in its more common and severe form, death occurs often by the age of two; while in milder forms SMA causes progressive and debilitating physical disabilities. While there is no current effective treatment available, there are several new drugs in clinical trials or entering the clinic in the next couple years. The Foundation staff is focused intently on these trials and much of our work revolves around development of tools and outcome measures that will help determine if an experimental drug is effective. My work specifically involves the development and validation of blood-based biomarkers for SMA, and it is our hope that the SMN ELISA will be part of the biomarker toolkit for several of these trials.”
Involved in the SMA Foundation kit’s development was Proteintech antibody 11708-1-AP, an anti-SMN rabbit polyclonal IgG. The antibody was of several screened by Kobayashi and her team intended to increase the sensitivity of the assay:
“When we screened 11708-1-AP, we found that it bound recombinant SMN antigen at a concentration that was nearly four times lower than the other antibodies tested. This allowed us to improve the sensitivity of the assay significantly and gave us an ELISA that we felt comfortable would give robust and reliable measurements.”
So would Dr. Kobayashi recommend the 11708-1-AP antibody? “The antibody has performed well, and also seems to bind to an epitope that differentiates it from several other commercially available SMN antibodies. I would recommend it, especially for researchers exploring new SMN assays themselves.”