Areas of Investigation
Neurological research at Gladstone focuses on a host of devastating conditions, including Alzheimer’s, frontotemporal dementia (FTD), Parkinson’s and Huntington’s disease, amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) and multiple sclerosis. In addition, Gladstone research has potential applications for spinal cord injury, stroke and traumatic brain injury.
Alzheimer’s is the most common neurodegenerative disorder and, in many ways, the most complex. We are therefore attacking Alzheimer’s on many fronts. Already, Gladstone has identified drugs that can counteract the detrimental effects of apoE4—the most important genetic risk factor for the disease. Other Gladstone investigators are working to move JM6—a new compound we developed to reduce the progression of both Alzheimer’s and Huntington’s diseases—into human trials. We also found that lowering brain levels of the protein tau improves memory and other cognitive functions in mice genetically engineered to mimic Alzheimer's disease. We are now investigating several therapeutic strategies to block tau's disease-promoting activities. Other studies identified additional ways to make the brain more resistant to amyloid-beta peptides that impair neuronal function as they build up in brains of those with Alzheimer’s.
Other Gladstone scientists are investigating the network of brain cells that controls movements to figure out how its dysfunction leads to the symptoms of Parkinson’s disease. These studies are yielding novel ways to keep this network functional when relevant brain cells and chemicals are lost as a result of the disease. We are also studying mitochondria, the energy-producing subunits of cells, as their impairment appears to play an important role in multiple neurodegenerative conditions, including Alzheimer’s, Parkinson’s and ALS.
Indeed, in much of our work, Gladstone scientists collaborate across disease areas. We find that scientific leads in one illness can inform work in another. We always look for common threads that might lead to better treatments for multiple conditions. For example, Gladstone scientists are researching how autophagy—a process by which cells eliminate abnormal proteins—can help to prevent the destruction of brain cells. This research may benefit people with Alzheimer’s, Huntington’s and other neurological disorders. And our Alzheimer’s research into apoE4 will likely have implications for the treatment of traumatic brain injury. We're also studying TDP-43, another protein that may contribute to diverse neurodegenerative disorders. Gladstone investigators also discovered that the p75 neurotrophin receptor—a protein long known for its role in the development of brain cells—plays unexpected roles in metabolic disorders, such as type 2 diabetes.
Several Gladstone scientists study abnormal inflammatory responses by immune cells in the central nervous system, which may contribute to the progression of multiple sclerosis, neurodegenerative disorders and many other neurological conditions. A related line of investigation focuses on the blood protein fibrinogen, whose transgression of the so-called blood-brain barrier appears to be an early trigger of multiple sclerosis and a potential contributor to numerous neurological disorders. Novel approaches to block its detrimental activities hold great promise for the treatment of multiple sclerosis, spinal cord injury, stroke and traumatic brain injury.