A researcher at the University of Missouri has made a promising breakthrough in the quest to help people with amyotrophic lateral sclerosis (ALS), the neurodegenerative disorder commonly known as Lou Gehrig's disease.
In a recent study, Mizzou's Smita Saxena showed that a natural molecule called GM1 can reach the brain when it's wrapped inside a tiny fat-based bubble. In early laboratory testing, this approach helped improve ALS symptoms.
The breakthrough could pave the way to one day begin human clinical trials at the Roy Blunt NextGen Precision Health building to see whether the new therapeutic approach could improve motor function for people with ALS.
A neural chain reaction
ALS is difficult to treat because the disease involves many breakdowns in the brain that compound over time, causing muscle weakness, slurred speech and fatigue.
"Our research team's previous work showed that neurons in those with ALS are very sensitive to endoplasmic reticulum stress, which limits the mitochondria's ability to produce energy," Saxena, a professor in the School of Medicine , said. "This, in turn, limits the ability of neurons to send messages across synapses when we want to move our muscles."
Those interconnected breakdowns are what ultimately cause the symptoms associated with ALS. Previous attempts to successfully deliver an ALS drug to the brain have failed because of the blood-brain barrier. This protective layer of cells between the bloodstream and the brain protects against entry from harmful pathogens and toxic substances but also can keep therapeutics from reaching the brain. That's why previous research attempts to deliver "extra" GM1 to the brain have failed.
Saxena's research seems to have overcome that hurdle.
She worked with InnoMedica, a biopharmaceutical company in Switzerland, to use a delivery system known as Talineuren — a microscopic lipid bubble with GM1 packaged inside. Because this delivery device has previously been used in a human clinical trial to give extra GM1 to patients with Parkinson's disease, Saxena wanted to repurpose the strategy for improving ALS symptoms.
And it worked.
When given to mice that had the same mutation that causes ALS, the therapy successfully crossed the blood-brain barrier and improved the health of their motor neurons, helping them move better.
If clinical trials prove the therapy is effective in slowing down the disease, researchers envision that it could one day be given to younger individuals who have inherited the disease-causing mutation, potentially halting ALS before symptoms emerge. Encouragingly, the therapy has already demonstrated strong safety and tolerability in a clinical trial involving Parkinson's disease patients.
Mizzou makes this work possible, Saxena said.
"The NextGen Precision Health building is the perfect place for this research," she said. "By having research and clinical space under the same roof, we can speed up the process for translating foundational research into human clinic trials to ultimately help improve quality of life for Missourians and people worldwide."
"Engineered GM1 intersects between mitochondrial and synaptic pathways to ameliorate ALS pathology" was published in Advanced Science.
