Announcement • Apr 08
Alzamend Neuro, Inc. Reports Encouraging Pharmacodynamic Data From Phase II Clinical Trial Of AL001
Alzamend Neuro, Inc. announced encouraging pharmacodynamic findings from a brain magnetic resonance spectroscopy analysis conducted in healthy human subjects (N=6) in a trial conducted at Massachusetts General Hospital. The study assessed changes in five key brain metabolites across 18 brain regions when participants received two-weeks of blood bioequivalent and lithium-dose equivalent AL001 or lithium carbonate relative to baseline. Early data suggest AL001 may work like lithium carbonate by selectively impacting brain chemicals where needed, however, AL001 appears to be leaving other, healthy brain chemicals more undisturbed than lithium carbonate, a potentially meaningful tolerability advantage. These interpretations are based solely on qualitative review of all analyses and need to be further statistically confirmed in additional patient populations, the first of which is currently underway. When participants took AL001, multiple brain chemicals trended downward, while the same chemicals trended upward in those same participants when they took lithium carbonate. This suggests that AL001 may interact with the brain in a distinct manner and have a less disruptive effect on healthy brain tissue than lithium carbonate. Both AL001 and lithium carbonate reduced levels of a key brain chemical called myo-inositol - which is exactly what lithium-based treatments are supposed to do. Notably, AL001 affected this target in nearly twice as many brain regions (17 out of 18) as lithium carbonate (8 out of 18), suggesting AL001 may deliver lithium's intended benefits more broadly throughout the brain. Glutamate, a key chemical messenger in the brain, was largely undisturbed in 10 of the 18 brain regions of patients after two-weeks of AL001, while two-weeks of lithium carbonate seemed to have caused disruptions to glutamate levels across every brain region measured. Keeping glutamate stable is important for long-term brain health, which suggests AL001 may have fewer side effects than lithium carbonate over time, however, this needs confirmation over a longer duration of exposure. Based on these initial findings, Alzamend has identified the following pharmacodynamic hypotheses to be tested in future confirmatory studies involving subjects with Alzheimer's, BD, MDD and PTSD: AL001 causes less disruption to healthy brain tissue than lithium carbonate, potentially resulting in fewer side effects and better long-term tolerability; AL001 produces the same beneficial brain response that makes lithium an effective treatment, by reducing a key brain chemical, myo-inositol, suggesting it works through the same proven mechanism of action as lithium carbonate, just with a potentially better safety profile; AL001 appears to leave glutamate levels in healthy brain tissue largely undisturbed, a potentially important advantage over lithium carbonate, which appears to disrupt glutamate broadly. Stable glutamate levels in healthy tissue may mean fewer cognitive side effects and better long-term tolerability for patients; and unlike lithium carbonate, AL001 may help preserve the health of brain cell membranes in healthy tissue, the protective outer layer of brain cells that play a critical role in how they function and communicate. If confirmed, this could mean AL001 is better tolerated by patients over the long-term than lithium carbonate. AL001 is Alzamend's patented ionic cocrystal formulation of lithium combined for delivery with L-proline and salicylate, which is designed to deliver a full therapeutic amount of lithium to the brain with less systemic exposure than lithium carbonate, potentially enabling a safer, better-tolerated therapy across Alzheimer's, BD, MDD and PTSD. Brain metabolite concentrations were assessed using ultra-high field high-resolution magnetic resonance spectroscopic imaging (MRSI) in six healthy volunteers following blood-bioequivalent and lithium-dose equivalent 14-day multiple doses of AL001 and lithium carbonate treatments in a randomized, crossover design across 18 brain regions. The five metabolites analyzed were: total creatine (Cr+PCr), glutamate (Glu), glycerophosphocholine plus phosphocholine (GPC+PCh), myo-inositol (Ins), and N-acetylaspartate plus N-acetylaspartylglutamate (NAA+NAAG). Statistical analyses used the Wilcoxon signed-rank test and Hedges' g effect-size measure, with a pre-specified =20% absolute threshold to screen for pharmacodynamically relevant signals. The MRS neuroimaging methodology was developed by the lab of Dr. Ovidiu C. Andronesi, the study's principal investigator, Associate Professor of Radiology at Harvard University, and the Director of Multinuclear MR Imaging, Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School. All findings are exploratory, hypothesis-generating, and require confirmation in adequately powered studies.
