Scientists Step up to the Plate in the Fight Against ALS

Until this week, most medical text books and online publications agreed that in 90- 95% of  amyotrophic lateral sclerosis (ALS) cases, the disease occurs at random with no clearly associated risk factors.

Now, according to a study published in the Journal of Experimental Medicine, scientists have discovered two proteins that can conspire to promote the invariably fatal neurological disease.

ALS, or Lou Gehrig’s disease, is a rapidly progressive, devastating neurodegenerative disorder that results in progressive loss of motor function and ultimately death.

Jean-Pierre Julien and colleagues at Laval University in Quebec now find that a protein called TDP-43 binds to an inflammatory protein called NF-kB p65 in the spinal cords of ALS patients but not of healthy individuals.

TDP-43 and p65 were also more abundant in ALS than healthy spinal cords.  It appears that TDP-43 and p65 cooperate to ramp up production of factors capable of promoting inflammation and killing nearby neurons.

Treatment of TDP-43 mice with Withaferin A, an inhibitor of NF-κB activity, reduced neuron loss and denervation and ALS disease symptoms.

These findings highlight p65 as a potential therapeutic target for this debilitating disorder which currently affects as many as 20,000-30,000 people in the United States and the additional 5,000 people who will be diagnosed with the disease each year. ALS is one of the most common neuromuscular diseases affecting people of all races and ethnic backgrounds. ALS most commonly strikes between 40 and 60 years of age, and men are affected more often than women.

SRxA’s Word on Health will be following this story and bringing you news on further advances in the fight against ALS, as they break.

Did Lou Gehrig have Lou Gehrig’s Disease?

Ridiculous question?  Or perhaps not, according to new data published this week in the Journal of Neuropathology & Experimental Neurology.

The study, involving 36 subjects, suggests that some patients may be misdiagnosed with amyotrophic lateral sclerosis (ALS) a form of motor neuron disease also known as Lou Gehrig’s disease.  Instead they may have a newly characterized disease called chronic traumatic encephalopathy (CTE).  CTE, a central nervous system disease, is thought to occur as a result of repeated concussion-like trauma.

TDP-43

The researchers used sophisticated neuropathology techniques to study the proteins – tau and TDP-43, in brains obtained at autopsy from twelve former athletes. Eleven of the athletes had been professional football players or boxers; one was a hockey player.

All of the athletes had CTE, with dementia developing many years after a history of repeated concussions. Three of the athletes were also affected by fatal motor neuron disease, with profound and progressive muscle weakness and deterioration for several years before death. The brains from patients with CTE and motor neuron disease showed specific patterns of tau and TDP-43 deposits, distinct from those of sporadic ALS.

Of course, most people who develop ALS are not pro athletes. “The study has broad implications, not only for understanding the potential risks to professional and non-professional athletes in many types of collision sports, but also for people who serve in military combat,” said Dr. Raymond A. Sobel, Editor-in-Chief of Journal of Neuropathology & Experimental Neurology. “Anyone who experiences repetitive, seemingly mild, head injury or concussion might be at risk for developing a brain disease later in life.”

However, some critical research questions remain. It’s still unknown exactly how brain injury leads to protein deposits, or whether head trauma produces these changes alone or in association with certain genetic factors.

What is known and clearly documented is that Lou Gehrig suffered significant concussions playing baseball and was notorious for playing through such injuries. Could he have been an early victim of CTE?

Sadly, Word on Health can’t answer this.  According to biographers his remains were cremated and thus cannot be studied.