Science

Neurons converted from astrocytes
Neurons converted from astrocytes

Unmet Medical Needs in Neurological Disorders

Unmet Medical Needs in Neurological Disorders

Neurological disorders such as Stroke, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Spinal cord injuries (SCI) have inflicted millions of patients in US and even more patients worldwide. The medical and financial burdens are tremendous not only to the families but also to the entire society. Stroke is the leading cause of long-term disability in US, with nearly 800,000 people experience a stroke each year and seven million stroke survivors in total. Alzheimer’s disease is also rapidly growing in US and around the world, with 5.7 million patients in US and the number is continuously increasing significantly each year with growing aging population. The annual cost of care for Alzheimer’s patients in US is projected to be $277 billion in 2018 and over one trillion dollars by 2050.

Loss of functional neurons is the common feature of acute neural injuries and neurodegenerative diseases. The inability of neurons to replenish themselves brings the greatest challenge in the treatment of neurological disorders. The current therapeutic approaches are mostly trying to prevent or slow down the neuronal loss but cannot regenerate many new neurons once neurons are lost. Thus, there are no effective treatments for neurodegenerative diseases such as AD and ALS or neural injuries such as stroke. Developing a new technology to regenerate functional new neurons has been the long-time pursuit of the researchers in academics and industry.

In Situ Transdifferentiation (Cell Conversion) – Revolutionary Approach

Neural tissues contain two major types of cells, neurons and surrounding supportive glial cells. In development, both neurons and astrocytes differentiated from neural stem cells and they share many similar traits. However glial cells can divide and replenish themselves while neurons cannot. In diseased or injured neural tissue, the glial cells become reactive and proliferative after neurons become injured or die. Our technology converts those reactive glial cells next to the lost neurons directly into new neurons through manipulating their gene expression profile.

Neurons and astrocytes
Neurons and astrocytes

The conversion can be induced in two ways, by introducing a neural transcription factor NEUROD1 through adeno-associated virus (AAV) based gene therapy, or by using a cocktail of small molecules. Both approaches silence glial gene expression in glial cells and turn on neural gene expression, ultimately turning glial cells into neurons. The newly generated neurons will mature in a few weeks to become functional and ultimately integrate into existing neuronal network.

With in situ direct conversion, our technology side steps the limitations associated with stem cell transplantation therapies. With large quantity of glial cells available at neural lesion sites, our gene therapy technology can generate sufficient number of functional new neurons to repair damaged brain and restore lost brain functions. Our preclinical studies have achieved success in a stroke model where up to 80% of ischemic injured neural tissue has been repaired and motor function / cognitive deficits have been significantly rescued.