Sunday I was fascinated by the "Sixty Minutes" episode on the Columbian extended families that inherited a genetic defect that causes early onset Alzheimer's, by the time they reach 45 years old.
Watching the episode, I was reminded of another case in which a young lady with a different genetic mutation caused her to be afflicted with Alzheimer's, at the age of 30 years old. Link to that article.
That young lady lost the ability to swallow, causing her to be hooked up to a feeding tube. She also lost the ability to move her limbs and recognize people. Dr. Alkon, currently President and Chief Scientific Officer of Neurotrope, (NTRP) was allowed under an FDA compassionate use program to treat the young lady. She was treated with a drug called bryostatin, which is not a statin, it activates PKC epsilon. Within a short time she was able to recognize people, extend her arm to reach out to her husband and begin to swallow. This allowed her to be removed from the feeding tube so that she could drink from a straw and eventually regain the ability to speak some words.
The activation of PKC epsilon activates the main amyloid degrading enzymes, ECE, neprilysin, and IDE while activating Alpha Secretase. Alpha Secretase has been a target for treating Alzheimer's. The problem has been finding a safe one. Eli Lilly's(LLY) and Biogen's (BIIB) drugs are monoclonal antibodies that inhibit amyloid beta. But Lilly's drug, solanezumab, just failed a major Phase III trial, showing it was no better at slowing down cognitive decline than placebo. Merck (MRK) has a BACE inhibitor that also inhibits amyloid beta. Neurotrope's bryostatin, in addition to degrading amyloid, also normalizes GSK3 beta. That mechanism prevents the hyperphosphorylation of tau. So you don't have to be a tauist or a baptist, bryostatin hits both targets.
Incredibly, bryostatin also activates growth factors in the brain, such as BDNF, NGF and IGF-1. This mechanism causes synaptogenesis. That allows the brain to restore damaged synapses and grow new synapses. The hope is that the damage caused by Alzheimer's disease may actually be reversed through this mechanism.
Dr. Alkon didn't start out by trying to find a drug to fight Alzheimer's. He was leading a department at the NIH trying to find out how to increase memory and he came upon PKC epsilon. PKC epsilon was the conductor in the center of the orchestra, arranging the different mechanisms to create the masterpiece of memory.
Take that, Eli Lilly and Biogen. You guys have to give your drugs extremely early in the disease, to have any hope of your drugs working, because you need to treat patients before any damage to the synapses has occurred. So far all those drugs have failed, and the excuse is always that they haven't been given early enough in the disease process. If bryostatin can reverse the disease in moderate to severe patients, the drug would be given in all stages. Perhaps even for prevention in the early onset mutations or APOE4 cases. Yes, Dr. Alkon even has performed preclinical studies showing that bryostatin can counteract the negative genetic mechanism of the APOE4 gene.
I can't wait to see the data that the company will be releasing in five months, April 2017, from their 148 patient Phase II placebo controlled trial. Multi modal efficacy of bryostatin targeting PKC epsilon, versus everyone else's drugs, that are just trying to hit one target. It isn't even a fair fight. Neurotrope's bryostatin, if approved, is a blockbuster for one of the largest unmet medical needs in the world today.
Disclosure: I am/we are long NTRP.