Currently, 95% of rare diseases don’t have an effective treatment. Progress is being made, but there is just so much ground to cover in rare disease research.
Studying rare diseases also provides critical insight into common diseases. By studying some of the molecular processes of rare conditions, we can better understand the same or similar processes in common diseases. For example, Marshall Summer, from the Rare Disease Institute at Children’s National Hospital (which is a partner with VTC), is studying urea cycle disorder, a rare condition. But in doing so, he is also advancing our knowledge of heart disease and respiratory disease.
The Fralin Biomedical Research Institute within the Virginia Tech Carilion School of Medicine (VTC) has made many contributions in the rare disease space. For Rare Disease Day on February 28th, the institute reflected on some of their notable progress, as well as their plans for future research.
CASK Disorder
CASK disorder is caused by a mutation in the CASK gene which is essential for proper brain development. Stephanie DeLuca has published an array of studies for CASK disorder. She directs the Neuromotor Research Clinic at VTC.
Recently, VTC researchers published a study which demonstrated a novel insight about this condition. The team found that CASK gene mutations don’t change brain development. Instead, these gene mutations cause an early degeneration of healthy neurons.
This finding is critical because it changes how we should think about treatment. Now the task is to evaluate what biochemical process leads to the destruction of neurons and how to uncover how to stop that process.
DiGeorge Syndrome
DiGeorge syndrome occurs when a part of the 22nd chromosome is missing. It leads to improper development of the limbs, heart, brain, head, and more. This condition is Anthony-Samuel LaMantia’s specialty.
A recent study from LaMantia and his team has demonstrated that this syndrome hinders the creation of movement-sensing and pain-sensing neurons within the cranial nerve.
He has also collaborated on a study which shows the connection between the condition and autism in mouse models. He and his team uncovered that the condition diminishes connections in the cerebral cortex, which is responsible for mediating cognitive behaviors.
The researchers ultimate aim is to deeply understand the causes of the symptoms of this condition, and through this understanding, improve quality of life for patients from an early age.
Brugada Syndrome
Burgada syndrome impacts the electrical signaling in the heart and can cause sudden cardiac death. It is caused by mutations in the SCN5A gene, which is responsible for regulating sodium channel function within the heart.
Steven Poelizing and his team are currently working to investigate how these faulty sodium channels may alter heart rhythms.
Long QT Syndrome
Poelzing is also studying Long QT syndrome which is caused by SCN5A gene mutations as well. This condition causes a lengthened Q-T interval which means it takes too long for the electrical pathways in the heart to depolarize after a heartbeat.
Poelizing and his research team are studying the precursors to arrhythmias and cardiac death in these patients. They have recently found that for dangerous arrhythmias to occur, three things have to happen simultaneously – high blood sodium levels, sodium channel dysfunction, and heart tissue swelling.
Glioblastoma
Glioblastoma is an aggressive and fast-growing brain tumor which can lead to symptoms of stroke and even death. Fewer than 1 in 10 survive 5 years past diagnosis.
Zhi Sheng from VTC has developed a new therapeutic approach which combines peptides and chemotherapy.
Samy Lamouille and Rob Gourdie are also working on ways to improve treatment for this cancer. They are working on a stem cell approach. Stem cells are very resistant to cancer treatments, but this means if they’re left after treatment, they’ll quickly lead to reoccurrence. These researchers are developing a new peptide drug which specifically targets stem cells.
Diffuse Intrinsic Pontine Glioma
Diffuse intrinsic pontine glioma (DIPG) is a rare brain cancer. Most patients don’t live more than 5 years. The tumors are treatment resistant and often can’t be operated on because they develop within the brainstem.
Jennifer Munson studied how to use an ultrasound, sonodynamic therapy, and chemotherapy to treat this condition. Jia-Ray Yu and his team uncovered how the condition originates. Yu found that for 80% of people with this condition, the cancer forms from a single cell which has a histone gene defect. This defect has a chain reaction which changes healthy brain cells into cancer.
You can read more about this work in rare disease here.
