My Alzheimer's Journey
Part 115 - A Potential New Alzheimer's Therapy From Stanford University
Frank Longo, MD, PhD, is a professor of neurology and neurological sciences at Stanford University. Actually, Dr. Longo is much more than just a professor.
He and his team of researchers have spent years studying various mechanisms that seem to slow the damage to and loss of brain synapses (small pocket of space between two cells, where they can pass messages to communicate). Dr. Longo believes this approach will counter Alzheimer’s and other neurodegenerative diseases.
The human brain is said to contain about 86 billion neurons and at least hundreds of trillions of synapses. During fetal and early childhood development, many more synapses are created resulting in extreme redundancy. While this redundancy can impede cognition, there is a neurotrophin receptor (p75NTR) that in very simple terms trims or prunes the excess synapses.
According to a study published in Nature Neuroscience in November 2022, p75NTR slows down (becomes dormant) after childhood development. Yet, as we age the receptor gradually becomes more active. This leads to a loss of cognitive function.
Dr. Longo and his team studied a family in Columbia who had an unusually high number of Alzheimer’s stricken members. The family members had inherited a mutation causing their brains to massively overproduce amyloid-beta. One member of this family who had large amounts of amyloid-beta remained Alzheimer’s free for decades. It was determined that this person had a gene that controls many of the same nerve cell signaling mechanisms regulated by p75NTR. Dr. Longo set out to find a synthetic mechanism that would target p75NTR and create a resilience to amyloid-beta.
A compound (LM11A-31) was eventually developed that is designed to block the activity of p75NTR. Stanford does no commercial-development work, so Dr. Longo co-founded PharmatrophiX Inc. with his wife, CEO Anne Chun Longo. PharmatrophiX has an exclusive license agreement with Stanford to develop LM11A-31.
Between 2017 and 2020, a Phase 2a clinical trial primarily focused on the safety of LM11A-31. The trial had 242 participants with mild to moderate Alzheimer’s. Participants were randomly assigned to one of three groups: a placebo group, a group receiving 200 mg of LM11A-31, or a group receiving 400 mg. Each participant took two pills daily for 26 weeks. The trial concluded that the drug is safe and tolerable enough for larger trials.
This study was focused on safety and tolerability; however, the participants completed cognitive tests to begin to explore potential effects of LM11A-31. Results showed no significant difference between the drug and placebo groups in cognitive performance. However, further analyses revealed that participants taking LM11A-31 had lower levels of beta-amyloid and tau, compared to those who received the placebo. Brain scans also showed smaller reductions in gray matter and glucose metabolism in key brain regions among those taking the drug.
“The plaque-attack drugs are narrowly focused on removing amyloid,” Longo said. “That’s only one of several parallel mechanisms causing the neurodegeneration. LM11A-31 slows down a broad range of the degenerative cascade.”
PharmatrophiX is working on funding a Phase 3 clinical trial of LM11A-31 in Alzheimer’s patients.
“LM11A-31 could really be a breakthrough if it gets through Phase 3. If it’s successful, it will be the first neuroprotective drug to prove itself for Alzheimer’s disease.”said Howard Fillit, MD, a co-founder and the chief scientific officer of the Alzheimer’s Drug Discovery Foundation.
I will continue to follow PharmatrophiX as they raise the funds for the Phase 3 trial.
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