Research and Development
Multi Modal Efficacy
Bryostatin-1 activates Synaptic Growth Factors – BDNF, NGF, IGF, others. It also activates all amyloid-β Degrading Enzymes (ECE, Neprilysin, IDE). Bryostatin also activates α-secretase, which reduces formation of neurotoxic amyloid-β formed by γ-secretase and BACE. ApoE3 induces PKCϵ; by activating PKCϵ, so there is an increase in BDNF expression. Bryostatin blocks ApoE4 reduction of BDNF via HDAC inhibition. Bryostatin normalizes GSK3-β, thereby inhibiting pathological Tau protein transformation into neurofibrillary tangles (NFTs).
Studies have demonstrated that PKCϵ plays a pivotal role in learning and memory. Bryostatin, a small molecule, penetrates the blood-brain barrier and activates PKCϵ, resulting in Improved synaptic function, promotion of new synapse formation, maturation of immature synapses and repair of damaged synapses. PKCϵ protects against synaptic and neuronal loss, degrades toxic beta amyloid, enhances new synapses and memory, prevents neurofibrillary tangle formation. Preclinical work at BRNI demonstrated improved memory and learning in multple different Alzhiemer's mouse models and several other animal models.
Safety data from >1,500 patients in NCI-sponsored clinical trials and FDA approved Compassionate Use protocols in severe Alzheimer's disease patients. Three patients treated, longest dosed patient approximately one year. Significant improvement in cognition and activities of daily living over treatment period.
Bryostatin is currently being tested in a 148 moderate to severe Alzheimer's disease patient population across 26 sites in the U.S. First patients dosed January 2016 and now fully enrolled. Primary efficacy endpoint based on Severe Impairment Battery Scale (SIB). Entry criteria based on the MMSE score. Secondary efficacy endpoints – Activities of Daily Living (ADL), Neuropsychiatric Inventory (NPI) and Mini-Mental State Exam (MMSE). Top line data expected in April 2017.
Science That Truly Matters; Innovation is at the Core
Patients suffering from severe Alzheimer’s disease is a key concern for us. Neurotrope has taken a lead position in the global Alzheimer’s disease development pipeline.
- Neurotrope has successfully completed its first Alzheimer’s Trial.
- Neurotrope has advanced two Orphan Disease programs.
We have successfully completed a Phase 2a trial.
Fragile X Syndrome (FXS) is a devastating genetic disorder with a prevalence (existing cases) in the U.S. of about 135,000 persons. FXS shows a combination of the following signs in children and throughout life including developmental delays, intellectual and learning disabilities, anxiety, and autism spectrum disorders. In multiple FXS animal models it was shown that Bryostatin 1 improved memory and learning. Neurotrope is expanding on the BRNI preclinical data to show that Bryostatin 1 improves behavior in a collaboration with the FRAXA Research Foundation. Neurotrope BioScience plans to institute a Phase 2 clinical trial in FXS patients early next year.
Niemann Pick Type C is both a debilitating and lethal genetic disease occurring in all ethnic groups. Its prevalence is estimated to affect about 35,000 children per year. Neurotrope is working with world renowned experts at the Icahn School of Medicine, Mt. Sinai to develop its lead compound, Bryostatin 1, as a potential treatment for the excessive accumulation of cholesterol and other lipids in the viscera and brain resulting in cell death and to neuologic symptoms, including difficulty in swallowing and speaking, loss of coordination, seizures, and progressive dementia. There is no FDA approved treatment for Niemann-Pick Type C.