Friday, 21 August 2020 14:45

Florida: New functional NMJ disease model proves the effectiveness of therapeutics against ALS Featured

The Hybrid Systems Laboratory at the University of Central Florida (UCF) has developed a human-on-a-chip model to study therapeutics against amyotrophic lateral sclerosis, which provides much faster and more reliable results than using an animal model.

Amyotrophic lateral sclerosis (ALS) is a still incurable degenerative disease of the central nervous system. The loss of motor neurons leads to paralysis and often to death within a few years. With the exception of rare hereditary forms, the cause of the disease is still unknown.

For the ALS model, human motoneurons from induced pluripotent stem cells of different ALS patients and muscle fibers of healthy volunteers were placed in small chambers of a microfluidic chip system. In the investigations, the motoneurons were stimulated with increasing frequency and the muscle response was monitored to detect both "jumps" and accelerated fatigue. In the ALS model, there was significant impairment of NMJ formation, hence an impaired transmission of electrical activity and muscle contraction.

The UCF scientists led by Prof. Dr. James Hickman were also able to show for the first time that although different ALS mutations show different phenotypes, they are all caused by a common origin deficit at a specialized synapse named NMJ, which is the link between alpha-motoneurons and skeletal muscles.

With their model, the researchers were also able to demonstrate the effectiveness of the so-called Deanna protocol for the treatment of ALS. In this protocol, the patients follow a special ketogenic diet as well as dietary supplements such as the neurotransmitter gamma-aminobutyric acid.

Original paper:
Xiufang Guo, Virginia Smith, Max Jackson, My Tran, Michael Thomas, Aakash Patel, Eric Lorusso, Siddharth Nimbalkar, Yunqing Cai, Christopher W. McAleer, Ying Wang, Christopher J. Long, and James J. Hickman (2020). A Human-Based Functional NMJ System for Personalized ALS Modeling and Drug Testing. Advanced Therapeutics 2000133,