Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis, or ALS, might damage muscle-controlling nerve cells in the brain earlier in the disease process than previously known, according to research from the Cedars-Sinai Medicine Institute. The findings could shift researchers’ attention from the spinal cord to the brain’s motor cortex as the disease’s initial point of dysfunction.
In the current study, the team showed the exact progression of ALS in animals that have an inherited form of the disease, and exposed the brain’s significant role in initiating the disease process thought previously to originate in the muscle or spinal cord.
The researchers did this by selectively removing the disease-causing mutation just from the brains of ALS animals, and found that this alone had a big impact on disease initiation and progression.
ALS causes weakness and gradual paralysis of muscles throughout the body, and although the timing and sequence of progression is unpredictable, it often begins in the arms or legs and eventually affects the breathing muscles in the chest. Patients generally live only three to five years after onset.
The disease is known to affect motor neurons, nerve cells that control muscles, in the brain, brainstem and spinal cord. It also inflicts damage in the nerve pathways extending from the spinal cord out to the muscles of the body. Breakdown of communication at the neuromuscular junctions, the points where nerve fibers connect to muscle fibers, is what ultimately leads to muscle weakness and failure.
In previous research using laboratory mice with the disease, the earliest, most obvious anatomical damage has been seen in the neuromuscular junctions and in the spinal motor neurons, called the lower motor neurons.
Most ALS research has focused on these areas. But recent studies in both humans and lab mice have suggested that motor neurons in the brain, the upper motor neurons, may be involved in disease progression, although the extent and significance of this involvement has remained unknown.
The current study was designed to better define the process by which ALS progresses and to explore the role of brain motor neurons in disease development and progression.
Most animal studies of the disease are conducted with laboratory mice that have been genetically engineered and bred to model ALS, but for this research, investigators used rats with ALS because they more accurately portray the disease’s variable course in humans.
The team found that spinal motor neurons die before symptoms begin and before nerve damage occurs between the spinal cord and the muscles. In fact, motor neuron death starts in the spinal cord and radiates out to the muscle and the brain over time. Motor neurons in the brain are not lost until the final stages of the disease, but starting very early in the process they appear to exist in a dysfunctional form.
When the team suppressed the ALS mutation in the brains of animals, onset of the disease was delayed, the animals lived longer, spinal motor neurons survived longer, and the neuromuscular junctions stayed healthy longer.
These results suggest that an early dysfunction of motor neurons in the brain may be a significant contributor to later disease development and progression, opening the possibility that experimental therapies targeting this ‘upstream’ dysfunction could have a beneficial impact on the disease’s catastrophic ‘downstream’ effects.
The team summise it is likely that dysfunction at a cellular level, without cell death, goes undetected for years prior to symptom onset and clinical diagnosis. It is imperative that the medical community identify patients at high risk of developing ALS and devise and initiate treatments that can intervene before an irreversible cascade of motor neuron circuitry failure sets in.
Source: Cedars-Sinai Medical Center
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.
Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.
Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.
Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.