A neglected population?

• The Jackson Laboratory has a Rare and Orphan Disease Center to address conditions that, while individually rare (by definition, affecting fewer than 200,000 people in the U.S.), collectively affect about one in 10 Americans, according to the National Association for Rare Disorders, and thus represent a major health issue.
• About 80 percent of rare diseases are genetic in origin, about half affect children, many are fatal, and very few have cures. Rare conditions are often described as “orphan” because they receive relatively little attention and investment from pharmaceutical companies.

JAX Research: Bringing a start-to-finish approach to understanding the genetic basis for rare inherited conditions

Developing custom genetic tools that bring real hope to families with rare diseases

When patient families search online for research programs in a specific rare genetic condition, JAX may be the only “hit” they get. That’s because JAX is an international resource for research in rare diseases, a role that includes developing and providing mouse models, data and drug-development services.

Neuroscientist Cat Lutz, Ph.D., is the director of the JAX Rare and Orphan Disease Center, and she works closely with many rare disease foundations and researchers to support their research and drug discovery goals.

Research by Lutz and her collaborators led directly to the development of Spinraza, the first FDA-approved drug to treat spinal muscular atrophy (SMA). Her team is developing new mouse models for multiple rare and orphan diseases, including a severe neurological disorder due to a mutation in a gene called KIF1A; Snyder-Robinson Syndrome, a rare developmental condition; and CMT4J, a variant of Charcot-Marie-Tooth disease.

“When you see kids with SMA actually walking and playing, who without treatment probably would not even be alive, that’s why we work so hard,” Lutz says.

Identifying potential new strategies for treatment of rare diseases

JAX Professor and neuroscientist Rob Burgess, Ph.D., studies Charcot-Marie-Tooth (CMT) disease, which causes damage to the bundles of nerve cell fibers that connect the brain and spinal cord to muscles and sensory organs.

Affecting one in about 2,500 people each year, CMT includes more than 80 different genetic mutations, each with very different disease processes and symptoms. Currently, there are no cures. 

Knowing that the first step to developing drug therapies is to find the mouse model with a genetic profile that most closely resembles each CMT variant, the Burgess lab is accelerating the creation, distribution and use of high-priority mouse models for CMT research. 

Rob has also worked to identify a combination of specific genetic mutations in Charcot-Marie-Tooth disease that worsens peripheral nerve damage. It may ultimately be a helpful biological marker for predicting the severity of disease in different people with CMT.

Knocking out rare neuromuscular diseases

Neuromuscular diseases start by hampering mobility and progress to threatening vital processes like breathing and swallowing. Spinal muscular atrophy (SMA) may strike in infancy, Duchenne muscular dystrophy (DMD) in early childhood or amyotrophic lateral sclerosis (ALS) in middle age. There are may be hundreds of other neuromuscular diseases, some exceedingly rare.

And JAX Associate Professor Greg Cox, Ph.D., wants to knock them all out.

Cox is at the hub of a network of researchers, mouse model experts, clinicians and patient families, all dedicated to finding the genetic causes and potential treatments for neuromuscular diseases. In his own lab Cox focuses on SMA and its very rare variant, spinal muscular atrophy with respiratory distress (SMARD), as well as ALS and DMD.  

“The fact that we have mice that develop the same disease symptoms and carry mutations in the same genes helps us to test many different therapeutic strategies in a relatively short time,” he says.

Cox has identified mutations in two mouse models showing symptoms of ALS. These mutations appear to affect accurate production of proteins in motor neurons, and they correspond to genetic variants found in some ALS patients.