The path to getting a medicine to the clinic is long and winding. To navigate it successfully requires teamwork and collaboration each step of the way. Our work on a childhood genetic disease called spinal muscular atrophy (SMA) illustrates how our Research Platforms —distinct groups of scientists with specialized technical skills and research expertise ranging from chemistry to pharmacology to toxicology- worked together to bring an investigational compound to the clinic, offering hope to patients who previously had none.
SMA causes a progressive loss of muscle function, due to the loss of motor neurons in the spinal cord. There is no cure for this disease, which is the most common genetic cause of childhood death.1 New therapies are desperately needed.
Right from the start, the SMA project was propelled by collaboration, says Rajeev Sivasankaran, Senior Investigator in the Neuroscience group at the Novartis Institutes for BioMedical Research (NIBR). Then part of the Developmental & Molecular Pathways (DMP) platform group, Sivasankaran and his associates first designed an assay to identify compounds that could correct the genetic defect that causes neuronal death in SMA. Members of the DMP team are experts at designing and running screens for potential drugs with a desired biological effect. The assay was then optimized for high throughput screening with the help of another Research Platform, the Center for Proteomic Chemistry (CPC).
I work with people all across the organization. Whenever something comes up that’s outside my wheelhouse, I know I can call an expert in that field.
After successfully identifying a candidate compound, Sivasankaran’s team enlisted the Global Discovery Chemistry (GDC) platform team, whose experts understand the chemical properties of potential new drugs. Together, the teams deciphered the relationship between the compound’s structure and its function. Armed with this information, the Metabolism and Pharmacokinetics (MAP) team determined the drug’s pharmacokinetic properties (how it is absorbed and metabolized in the body) in preclinical models, while the Preclinical Safety group assessed the safety of the molecule.
From there, the Translational Medicine, Drug Metabolism & Pharmacokinetics (DMPK) and Regulatory Affairs groups shepherded the investigational drug into human clinical testing. It is now being tested in infants with SMA in a clinical trial that began in April 2015.
Decision-making was a team effort throughout the project, according to Sivasankaran. “The DMP, GDC and MAP groups would sit together to hash out what kinds of studies needed to be done at each stage,” he says.
As with the SMA therapy, work from the Research Platforms often provides the starting point for clinical projects that are then picked up by the appropriate disease teams, explains Sivasankaran. This kind of teamwork is one of the more rewarding aspects of the job, say chemist Susan Swalley, who worked on the SMA project as part of the DMP group. “I work with people all across the organization,” she says. “Whenever something comes up that’s outside my wheelhouse, I know I can call an expert in that field.”