Jackson lab moves one step closer to ALS treatment

JACKSON — Medical research is a Sisyphean endeavor: Each study pushes the rock slightly farther uphill, until it finally reaches the top and a new discovery is made. Recently Brain Chemistry Labs, the nonprofit research lab in Jackson, moved the rock closer to the top of the hill.

In a study published in the Journal of Neuropathology and Experimental Neurology, research done on vervets, monkeys native to Africa, shows a toxin in cyanobacteria is associated with the misfolding of proteins found in patients with neurodegeneration. Perhaps more important, the study showed L-serine, an amino acid, slows the process of misfolding proteins.

“This experiment … is the missing link between cyanobacteria blooms and increased risks of ALS or Alzheimer’s,” Dr. Paul Alan Cox said. “Now we have causation.”

Cox runs Brain Chemistry Labs, but he’s not a neuroscientist. His work as an ethnobotanist, someone who studies the relationship between plants and human society, helped him develop the theory that BMAA — the cyanobacterial toxin — could in part cause neurodegenerative diseases.

That research, which followed several indigenous groups on Pacific islands, also gave him the idea that L-serine could slow the progression of the diseases. One of the groups he studied, the Ogimi, an indigenous tribe in Japan, had a low incidence rate of neurodegenerative diseases. The diet of the tribe consisted of food high in L-serine like seaweed.

Until now that idea had been just a theory. But the most recent study provides evidence the BMAA toxin causes the misfolding of proteins. Vervets that were given the BMAA toxin developed aggregations of the misfolded proteins seen in ALS patients, while those in the control group did not develop them.

The most heartening part of the research was a third group of vervets that was given both BMAA and doses of L-serine. Those animals still developed the misfolded proteins, but at a rate much lower than those in the group that received only the toxin.

Cox sees the results as a logical next step from a previous study Brain Chemistry Labs did with partners at Dartmouth University. That study followed 20 patients with ALS and was meant to show that L-serine was safe to administer, though it had other positive results, too.

“This explains why the first patients in our first clinical trial, they did really well on L-serine,” he said. “It slowed disease progression by 85%.”

Unlike Alzheimer’s, which often affects older people, ALS can develop in people in the prime of their lives. Fast moving, it causes paralysis and, eventually, death. Patients live an average of just two to three years following a diagnosis. In preliminary results, patients taking L-serine can live five to six years.

“That doesn’t sound like a lot,” Cox said, “but for the families it is.”

Having two studies that show L-serine slows the progression of neurodegenerative diseases doesn’t mean the amino acid is a cure. But the research inspires optimism in the scientists behind the work.

“The vervet BMAA model will be an important new tool in the quest for new drugs to treat ALS,” Dr. Walter Bradley, an author on the study, said in a statement.

Cox and his team don’t plan to rest on their laurels. They are already involved in several other efforts to further demonstrate the viability of L-serine as a treatment.

Following the initial 20-person clinical study, Dr. Elijah Stommel at Dartmouth is conducting a 50-person Phase II trial that should show results by year’s end.

“If we can replicate the results of the first trial,” Cox said, “we’d be tickled pink.”

Now that Brain Chemistry Labs has found a connection between BMAA and neurodegeneration, and a potential treatment, the further studies are the next attempts to push the rock uphill. They also have 40 patients in a Phase II clinical trial for Alzheimer’s, and are hoping to start a 100-person trial using L-serine to treat patients with mild cognitive impairment, a precursor to ALS and Alzheimer’s.

Should that research prove fruitful, Cox and his team will be one step closer to finding something that could slow such diseases.

“If we can slow the progression of mild cognitive impairment, it’s not a silver bullet,” Cox said, “but a preventative would be even better than a cure.”