After the ALS Ice Bucket Challenge drenched the world and spread the word, research efforts were reinvigorated. Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease, is a progressive and fatal disease that wreaks havoc between the brain, spine, and rest of the muscles in the body. Researchers at the Cedars-Sinai Board of Governors Regenerative Medicine Institute, have just discovered brain damage starting earlier than they thought, and published their findings in the Journal of Neuroscience. This could completely reroute their research efforts away from the spinal cord and to the brain’s motor cortex, where the disease starts to reveal problems.

"In this study, we show the exact progression of ALS in animals that have an inherited form of the disease, and we expose the brain's significant role in initiating the disease process thought previously to originate in the muscle or spinal cord," the study’s lead author Clive Svendsen, professor and director of the Board of Governors Regenerative Medicine Institute, said in a press release. "We 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."

Svendsen and his team found motor neurons in the spine start dying off before symptoms even begin to show in patients. The dysfunction travels into the spinal cord, which then sends damaged and delayed messages out to the arms, legs, and eventually facial muscles and those in the chest. Even though the motor neurons in the brain begin to have problems early on, they don’t actually start dying until the final stages of the disease.

After the arms and the legs stop receiving correct signals from the brain and spinal cord, they become useful. Soon after the ability to speak, eat, and breathe leave the person until all signals fail and they die. Understanding the origin and sequence of the dying neurons could slow down an otherwise quick death. ALS can strike anyone in the world regardless of race, ethnicity, or socioeconomic background. This has the potential to become a monumental stride in the fight for a treatment and cure. 

“When we 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," Svendsen said. If they could just block the ALS mutation in the brain from the start, it could slow the progression of degeneration in the rest of the body, or so they believe based on their animal studies.

The motor neurons in the brain stop working a lot earlier than scientists had originally thought. Svendsen believes this could be a significant contributor to how the disease develops in later stages. Treatment therapies may start in the brain in order to slow down the trickle effect they have on the rest of the body. Approximately 5,600 people are diagnosed with ALS in the United States each year. Patients usually only live two to five years after diagnosis, which is why there are only roughly 30,000 Americans living with the disease at one time, according to the ALS Association.

"It is likely that dysfunction at a cellular level, without cell death, goes undetected for years prior to symptom onset and clinical diagnosis,” the study’s coauthor Dr. Gretchen Thomsen, a scientist in Svendsen's laboratory, said in a press release. “It is imperative that we 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: Svendsen C, Thomsen G. Delayed disease onset and extended survival in the SOD1G93A rat model of ALS following suppression of mutant SOD1 in the motor cortex. The Journal of Neuroscience. 2014.