A New Approach to Alzheimer’s Disease

 
 

Allopregnanolone (ALLO) has potential to be a novel regenerative therapeutic for Alzheimer's disease. ALLO is a naturally occurring brain molecule that is produced in our body from the hormone progesterone. Both females and males are exposed to ALLO during fetal development and throughout their lifetime. ALLO can decline with age.

*Allopregnanolone is an “Experimental/Investigational drug” which means that the U.S. Food and Drug Administration (FDA) has not approved allopregnanolone for the treatment of Alzheimer’s disease beyond its use in this clinical trial.

Phase 1b/1a Clinical Trial Results

  • Allopregnanolone (ALLO) given once-per-week as an intravenous infusion was safe and well-tolerated in persons with  early Alzheimer’s disease. *

  • ALLO was well absorbed and reached the  highest concentration at 30 minutes and was undetectable after about 4 hours. *

  • Exploratory MRI brain Imaging indicated that ALLO treatment, once per week for 12 weeks, slowed brain (hippocampal) atrophy and in some cases increased volume of this brain region critical to cognitive function. **

    • Gain of hippocampal volume was evident in persons who carry the Alzheimer’s risk gene APOEε4.**

  • Multiple measures of white matter integrity indicated evidence of preserved or improved integrity.

    • ALLO significantly increased white matter fiber tract integrity primarily in the corpus callosum, bilateral thalamic radiations, and bilateral corticospinal tracts.**

    • Consistent with structural changes, ALLO strengthened local, inter-regional, and network level functional connectivity in brain regions vulnerable to Alzheimer’s, including the precuneus and posterior cingulate, and network connections between the default mode network and limbic system.**

    • Indicators of regeneration from previous preclinical studies and these exploratory MRI-based outcomes from this Phase 1b/2a clinical cohort support advancement to a Phase 2 proof-of-concept efficacy clinical trial of ALLO as a regenerative therapeutic for mild AD (REGEN-BRAIN© study; NCT04838301).**

*Hernandez, G. D. et al. Safety, tolerability, and pharmacokinetics of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: A single and multiple ascending dose phase 1b/2a clinical trial. Alzheimer's Dement (N Y) 6, e12107, doi:10.1002/trc2.12107 (2020).

**Raikes AC, Hernandez GD, Matthews DC, Lukic AS, Law M, Shi Y, Schneider LS, Brinton RD. Exploratory imaging outcomes of a phase 1b/2a clinical trial of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: Structural effects and functional connectivity outcomes. Alzheimers Dement (N Y). 2022 Mar 14;8(1):e12258. doi: 10.1002/trc2.12258.