Develop Exosome as Therapeutic Delivery Shuttle of Antisense Oligonucleotides for Amyotrophic Lateral Sclerosis
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurological disease with a prevalence of 5 cases per 100,000 persons and 5,000 new cases diagnosed each year in the United States. People who have served in the military are at greater risk (up to twice the chance) of developing ALS than those without military experience. The nerve cells (motor neurons) controlling voluntary muscle movements are primarily affected in ALS, which leads to muscle weakness, difficulties in speaking, eating, moving, breathing, and eventually to death. These nerve cells are hidden in the brain and spinal cord protected by a selectively permeable membrane named blood-brain barrier, which prevents entry into the brain of most drugs from the blood. Despite the development of drugs targeting the genetic causes of ALS, safe and efficient drug delivery is still a bottleneck in therapeutics for ALS. The proposed research aims to use a type of small vesicle called an exosome as a shuttle to deliver gene therapy drugs to the disease-relevant nerve cells in the brain and spinal cord, in a safe and efficient way. Exosomes are nano-sized vesicles released by all kinds of cells. These natural cell products function as messengers to transfer genetic cargo, including nucleic acids, proteins, and lipids, between cells in the body. Compared to the current drug delivery methods for ALS treatment, such as direct brain and spinal cord injections, the exosome-based delivery proposed in this study has several advantages. First, exosomes can protect drugs enclosed from degradation during circulation in the body. Second, exosomes can be efficiently taken up by recipient cells, which helps drugs to bypass biological barriers, including the blood-brain barrier and cell membranes. Third, drugs loaded into exosomes can be administered via intravenous injection, avoiding invasive direct injections into the brain or spinal cord. Last, but not least, exosomes derived from neural stem cells show therapeutic potential for neurological diseases, which will further enhance the therapeutic efficacy of the drugs to be delivered. Taken together, this study is expected to shape a safe and efficient drug shuttle to improve the delivery efficiency and therapeutic efficacy of gene therapy drugs, which can be widely used for treating ALS with a genetic base.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210261
Entities
People
- Yao Yao
Organizations
- The University of Georgia
- United States Army