Brain Regeneration Promoting Compound to be Tested in Alzheimer’s Clinical Trial

A research team at the University of Southern California (USC) will be initiating a Phase 1 clinical trial to test the effectiveness of their compound “Allo,” which promotes brain cell regeneration, in Alzheimer’s patients.

This new trial is one of four that are investigating new therapeutic targets in Alzheimer’s disease. These trials will also incorporate novel approaches to participant identification and selection.

These trials were reported at the Alzheimer’s Association International Conference in Boston. According to Roberta Brinton of USC, again and Alzheimer’s disease (AD) are characterized by a decline in the ability of the body to self-renew and repair (and this includes the brain). However, the capacity for regeneration is retained, albeit at a decreased level.

Allopregnanolone (3α-hydroxy-5α-pregnan-20-one), or Allo for short, is a neurosteroid that naturally occurs in the brain. Small quantities of it can also be found in the bloodstream. Previous studies have shown that Allo can improve cognitive function in older laboratory animals and in animal models of AD (see Chen S, Wang JM, Irwin RW, Yao J, Liu L, et al. (2011) Allopregnanolone Promotes Regeneration and Reduces β-Amyloid Burden in a Preclinical Model of Alzheimer’s Disease. PLoS ONE 6(8): e2429).


Robert Diaz Brinton, Professor of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering and Neurology at USC, reported the design of her clinical study at the Alzheimer’s Association International Conference. In this trial, participants diagnosed with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease will receive doses of Allo, administered once-per-week to establish a safe dose that is well tolerated.

Since Allo is already naturally synthesized in the brain, and reaches high levels during the third trimester of pregnancy, Brinton and her colleagues were able to circumvent the first few stages of safety testing. The secondary goals of this clinical trial include assessing potential short-term effects of Allo dosing on cognition and MRI indicators of AD. Such data will inform a Phase 2 proof of concept trial with MRI-based biomarkers of regeneration efficacy.

“Allopregnanolone is a well-characterized agent with a very promising track record of promoting neural stem cells generation and restoring cognitive function in animal models of Alzheimer’s,” said Brinton. “We consider Allopregnanolone a first class regenerative therapeutic for mild cognitive impairment and Alzheimer’s. Our hope is that, through further research, we will add Allo to the roster of Alzheimer’s treatments.”

One of the critical issues to consider in clinical trials such as this is the ongoing and relentlessly progressive burden of brain death caused AD. It is not sufficient to only generate new neurons and promote the survival of those neurons. It is also necessary to reduce the ongoing burden of the pathology of AD in order for treatments to accrue long-term benefits.

Brinton commented that “we were very encouraged to discover that Allo reduced the burden of Alzheimer’s pathology. Out findings are very exciting as they show that Allo increases the energy capacity of the brain. This is important because the generation of new neurons, new synaptic circuits and synaptic transmission all require substantial energy.”