Rare Disease Research at NIBR

Rare diseases are a key focus of the research strategy at the Novartis Institutes for BioMedical Research (NIBR) where scientists are currently investigating treatments for more than 40 rare diseases.

"We choose to work where there is unmet need and where the scientific understanding is strongest," said Mark C. Fishman, M.D., President of NIBR. "Unmet need can mean a rare disease with a small number of patients. Rare diseases have a huge impact on families, which has influenced me in focusing a significant portion of our research programs on these disorders."

NIBR scientists focus on fundamental biological mechanisms underlying disease. Most diseases result from defects or imbalances in a few dozen signaling pathways that have been conserved through evolution and control many of the basic cellular functions of life. By mapping these pathways, NIBR scientists look for openings to disrupt disease - for example, nodes or components so critical that, if disabled, they could cause the entire pathway to collapse.

The way new medicines are tested at Novartis can be as novel as the medicines themselves. "We might start with a very rare disease in what we call a proof-of-concept study," Dr. Fishman explained. A small-scale clinical trial, the proof of concept study allows a preclinical hypothesis about a drug's mechanism of action to be tested in a homogeneous patients group, providing a quick confirmation of potential therapeutic benefit. "If successful, we quickly extend development to other diseases in which the same mechanism is believed to be involved," Dr. Fishman added

Translating fundamental science into concrete therapies can lead researchers in unexpected directions. Novartis has one medicine under investigation that blocks particular receptors in the brain known as metabotropic glutamate receptors. Its main target helps ensure normal brain function but also is implicated in the pathology of a number of neurological diseases.

NIBR's translational medicine group completed a successful proof-of-concept study for this investigational medicine in Fragile X syndrome, the most common cause of inherited mental impairment. Importantly, the proof-of-concept study identified a biomarker that identified a subset of Fragile X patients who responded positively to it. A companion diagnostic test is being used in clinical trials.

"Using the biomarker and the companion diagnostic in clinical testing, we hope that we will be able to accurately predict each Fragile X patient's response to this investigational medicine," said Baltazar Gomez-Mancilla, MD, Executive Director, Neuroscience Translational Medicine at NIBR. "This is new for the field of Fragile X treatment and an encouraging step toward realizing a personalized treatment for these patients."