Newly discovered biomarker for Lou Gehrig's disease could lead to new therapy

Written by Loren Grush

A large degree of uncertainty still surrounds the disease amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig’s disease. A devastating illness with no known cause or cure, ALS only has a handful of treatments, and upon diagnosis, life expectancy is typically only three to five years.

For the first time, researchers from Brigham and Women’s Hospital in Boston (BWH) have identified a blood biomarker that could not only help to identify ALS earlier, but also help pave the way to new treatments that could significantly slow – or even stop – the progression of the deadly disease.

After conducting pre-clinical trials in mice genetically predisposed to develop ALS, the scientists discovered the secret lies in changes to the immune system and an increased production of white blood cells called monocytes. The animals’ spleens would start to exhibit proinflammatory qualities, producing a large influx of monocytes, which would then bombard the spinal cord – eventually getting into the brain.

ALS affects five out of every 100,000 people worldwide, typically those over the age of 50. According to the National Institute of Health, ALS is marked by the slow degeneration of muscle strength and control – making it difficult for people, over time, to perform simple tasks like taking steps or even swallowing.

Finding and controlling the monocytes

One of the main challenges for the scientists was being able to identify the monocytes after they entered the brain.

“There are really two cell types involved,” Dr. Howard Weiner, the director of the BWH Multiple Sclerosis Program and the study’s lead author, told FoxNews.com. “The macrophages or monocytes - these are cells that come from the [spleen] and go in to the brain. The microglia are already there in the brain and protect it from outside invaders. We discovered ways to distinguish between the two. Sometimes when [monocytes] come into the brain, you can’t tell the difference between [monocytes] and microglia. We found the difference and started to study them in the animal model.”

As the monocytes flooded the brain, they caused damage to nerve cells, eventually leading to the cells’ deaths. Weiner and his colleagues set out to decrease their production in the spleen.

“When we discovered the monocytes were coming into the brain and causing damage in the animals, we asked, ‘If we can affect those cells and change them – if we could decrease their inflammatory nature, could the animal do better?’” Weiner said of their process. “We’re reluctant to use the words cure, but it could slow down the disease and maybe stop it from progressing.”

After injecting the mice with antibodies to fight the spleen’s inflammation and tone down the monocyte production, fewer monocytes entered the spinal cord and less nerves cells were lost to damage. Ultimately, the antibodies helped to extend the mice’s life expectancy and overall survival.

Future treatments?

Not only does this have a profound impact on the future of ALS treatment, it also could be significant for the prevention of the disease’s onset. The scientists noted that the spleen became inflamed and started over-producing monocytes two months prior to when the mice started exhibiting brain damage – meaning testing for an increase in moncytes could help identify those who are about to develop ALS.

With such promising results from the study, Weiner and his colleagues hoped to see if they could translate their findings from the animal model to a human model.

“The next big question was, ‘What about people with ALS – do they have the same things?’” Weiner said. “We did blood samples of patients with ALS, and looked for the [genetic] profile and the inflammation in the animals. What was exciting was we saw virtually identical changes in the people - changes in the monocytes,…those certain gene signatures related to inflammation, we found them.”

As to why these monocytes get out of control, the research team cannot say for sure – meaning the cause for ALS is still unknown. But the discovery does help further the idea that the immune system plays a significant role in the development of neurological disorders.

“The monocytes are one of the cells in the immune system, and let’s say a bad virus comes in, you may need monocytes to block virus,” Weiner said. “The monocytes can get activated thinking there is an infection, and they can damage the normal tissue, even if there’s no infection. We think with Lou Gehrig’s disease, these monocytes somehow get activated with no infection and go into the brain and do damage.”

Weiner noted that while their discovery does not mean a cure is around the corner, he hopes to begin clinical trials on a new therapy within the next three years.

“We now have a blood test where we can test ALS patients for this inflammatory signature of monocytes in the blood. And we have a new target therapy to target these monocytes and stop them from going in the spinal cord,” he added.

“It gives hope that there’s a new avenue in new ways for ALS treatment.”