Rare disease research and treatment

A rare disease can be isolating when few people have it and there is no cure. The federal government considers a rare disease to be one that affects fewer than 200,000 people in the United States. By comparison, there are 400,000 children and adults with Down syndrome and at least 500,000 adults affected by Parkinson’s disease. What about the people whose condition is so rare, they may never meet another individual who shares their diagnosis? With support from the National Institutes of Health, Waisman Center investigators study rare diseases to discover the “why” of developmental disabilities and neurodegenerative diseases to develop treatments, therapies and cures.

In 2001, Waisman Center investigator and interim director Albee Messing, VMD, PhD, discovered the gene that causes Alexander disease, a rare and progressive condition that destroys white matter in the brain. Alexander disease is typically fatal and results from mutations in the gene known as GFAP (glial fibrillary acidic protein). The mutations cause abnormal protein deposits-Rosenthal fibers-to accumulate in nerve cells in the brain.

Alexander disease occurs in both males and females and there are no ethnic, racial, geographic, or cultural patterns to its affliction. The most common form of the disease occurs in infancy and usually becomes apparent during the first two years of life and is characterized by both mental and physical developmental delays, followed by loss of milestones, an abnormal increase in head size, and often seizures. The juvenile form of Alexander disease is less common and occurs between ages two and 12. Adult-onset Alexander disease is sometimes confused with multiple sclerosis or Parkinson’s disease before a definitive diagnosis can be determined by a blood test.

“We want to improve the lives of individuals and families who are affected rare diseases. Our scientists work in tandem to develop better treatments for the future,” says Messing.

In one project, researchers in Messing’s lab screen FDA-approved drugs with the hope of developing treatment options for Alexander disease from existing medications.

The Waisman Center community not only researches rare diseases but also provides clinical care and support to individuals and families affected by these conditions in the Waisman Center Clinics. The multidisciplinary clinical team is made up of professionals whose goal is to achieve the best possible outcome for development and health in children and adults with rare diseases.

Joyce Anderson is a member of the Waisman Center Grandparents’ Network (GPN), a forum for grandparents and family members to increase their understanding of developmental disabilities. Her grandson has Cornelia de Lange syndrome, a rare developmental disorder.  “It’s frustrating to have a family member who has a rare disease. We all want answers and they are hard to find,” says Anderson.  Although there is no active research on Cornelia de Lange syndrome at the Waisman Center, Anderson hopes that a discovery related to another developmental disability could benefit her grandson.  “The research, education and outreach of the Waisman Center are vital to our community.  It is applicable to anyone with a rare disease or syndrome.”

Qiang Chang, PhD, and Xinyu Zhao, PhD investigate a gene mutation that causes Rett syndrome, a rare neurological disorder that is a leading cause of intellectual disability in females, affecting one in 10,000 to 15,000 girls. Rett syndrome occurs more frequently in girls than boys and impacts parts of the brain that control learning, speech, movement, cardiac and pulmonary function, as well as swallowing and digestion. Rett syndrome is caused by mutations on the X chromosome in a gene important to nerve cell development called MECP2.

Zhao’s research shows that faulty gene production has a significant negative impact on brain development and function in not only Rett syndrome but also in fragile X syndrome and autism.

“Rett syndrome and autism share characteristics such as repetitive behaviors and communication delays. What we learn from studying Rett syndrome can help us to better understand autism as well,” says Zhao.

Rett syndrome can cause mild to severe disability depending on the gene mutation’s location and it is often first recognized in infancy when a child’s development slows. An infant with Rett syndrome may have a slow rate of head growth or low muscle tone. As they grow, the child may experience other health issues including seizures and labored breathing.

Chang researches non-genetic factors that cause MECP2 to behave differently in brain development and function. To analyze the treatment potential of a drug, Chang’s lab created a cell model of Rett syndrome with induced pluripotent stem (iPS) cell lines from female patients with Rett syndrome. By investigating Rett syndrome at a cellular level, Chang hopes to show how Rett syndrome occurs and to screen drugs for the possible treatment of Rett syndrome.