Neurological Disease

NEUROLOGICAL DISEASE

Diseases that affect the brain or other components of the central nervous system are among the most devastating and complex conditions plaguing mankind today. As populations around the world live longer, diseases related to aging present an unprecedented challenge. Estimates indicate that the number of those who suffer from Alzheimer’s around the world will double to 34 million by 2025, while the number of people in the United States alone who have Alzheimer’s disease is expected to nearly triple to 16 million by 2050. Numbers are also rising for those with Parkinson’s disease, which afflicts an estimated 10 million worldwide. Huntington’s disease is less common, but does strike about 1 in 10,000 and is the most frequent inherited neurodegenerative disorder.

At Gladstone, we focus on these diseases and others—such as frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) and multiple sclerosis—with urgency. And we have discovered much. For example, we have identified processes that can explain why apolipoprotein (apo) E4 is the main genetic risk factor for Alzheimer’s disease and also worsens outcome after traumatic brain injury. These findings have culminated in the computer-aided design of compounds that can block detrimental apoE4 effects. Related studies have elucidated how proteins that build up to abnormally high levels in the brain of Alzheimer patients—amyloid beta, tau and alpha-synuclein—interact to disrupt brain function and promote memory loss. We have turned conventional thinking on its head by revealing that the clumps of proteins, known as inclusion bodies, found in the brain of those with Huntington’s disease are actually part of a defense mechanism against the disease—rather than its cause.
We have developed a compound that in animal models protects against signs of Huntington’s and Alzheimer’s. Our scientists have also pointed the way to a new therapeutic strategy for multiple sclerosis and other neurological diseases by identifying that a blood protein, fibrinogen, plays a causal role in damaging the central nervous system. And just recently, a Gladstone scientist developed methods to convert adult skin cells into neurons that are able to transmit electrical signals—expanding capabilities in regenerative and personalized medicine.
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