An experimental drug has shown early promise in treating brain injuries caused by repeated blast exposure, a common issue among military personnel.
Pre-clinical research found the drug reduced harmful brain proteins linked to long-term cognitive decline and showed potential to ease brain inflammation in animal models.
Mild traumatic brain injury (mTBI) related to military service often leads to lasting physical and emotional problems and raises the risk of dementia later in life.
The findings come from a study of ALPHA-1062, developed by biopharmaceutical company Alpha Cognition, supported by the US Department of Defense and conducted in collaboration with US Department of Veterans Affairs investigators and the Seattle Institute of Biomedical and Clinical Research.
The drug reduced brain levels of three toxic forms of tau protein — abnormal proteins that build up in the brain following injury. One type, pTau 217, is thought to indicate greater risk of long-term cognitive decline and is among the earliest markers of Alzheimer’s disease.
A second form, pTau-S202/T205, appears in early Alzheimer’s pathology before plaques and tangles — clumps of proteins that damage brain cells — are visible. The third type, pTau 231, is elevated in both early Alzheimer’s disease and TBI.
Additional benefits were also observed. High doses of ALPHA-1062 reduced levels of myeloid cells and astrocytes — types of brain cell involved in inflammation and tissue repair. These changes suggest the drug may help limit damaging brain inflammation after injury.
ALPHA-1062 also increased expression of nerve growth factor receptors, which support brain cell survival. The effect was dose-dependent, meaning it grew stronger with higher doses.
“These outcomes are in agreement with those of an earlier pre-clinical study in a moderate TBI animal model, both studies demonstrated protective effects of ALPHA-1062, providing support for the continued development of ALPHA-1062 for the treatment of traumatic brain injury,” said Denis Kay, the company’s chief scientific officer.
While the results suggest ALPHA-1062 may help reduce the impact of TBI and potentially lower the risk of Alzheimer’s disease, human trials will be needed to confirm this.
Next steps for Alpha Cognition include completing formulation of a sublingual version of the drug — designed to dissolve under the tongue — and conducting a bridging pharmacokinetic study comparing it with both ZUNVEYL (benzgalantamine) and an intranasal version of ALPHA-1062.
The company already has US FDA approval for ZUNVEYL, a delayed-release oral tablet version of ALPHA-1062 used to treat Alzheimer’s. It is designed to cause fewer gastrointestinal side effects than existing acetylcholinesterase inhibitors.
ALPHA-1062 works by preventing the breakdown of acetylcholine, a brain chemical important for memory and learning. It also binds to alpha-7 nicotinic receptors, which the company says may support cognitive function.
