Alpha Cognition Reports Promising Preclinical Results for ALPHA-1062 in Military-Related Mild TBI Model
Alpha Cognition Inc., a biopharmaceutical company focused on developing innovative treatments for neurodegenerative disorders, has announced encouraging preclinical data supporting the continued development of ALPHA-1062 for the treatment of mild traumatic brain injury (mTBI). The findings demonstrate the potential of ALPHA-1062 to treat repetitive blast-induced brain trauma, a type of injury highly relevant to military service members and veterans.
The data not only highlight the drug’s neuroprotective effects but also suggest a possible role in reducing the long-term risk of dementia, including Alzheimer’s disease, which is significantly elevated in individuals with a history of mTBI.
Repetitive Blast Trauma: A Major Military Health Concern
Mild traumatic brain injury, particularly resulting from repetitive blast trauma, is one of the most common injuries among active-duty military personnel and veterans. This type of injury is often referred to as the “invisible wound” of war, as it may not always be immediately apparent but can lead to persistent physical, emotional, and cognitive symptoms.
Long-term consequences of mTBI can include:
- Impaired memory and executive function
- Increased risk of mood disorders such as depression and anxiety
- Heightened vulnerability to neurodegenerative conditions, especially Alzheimer’s disease
Given the significant impact on both patients and their families, there is a pressing need for targeted therapies that can treat the underlying pathology of mTBI rather than simply managing its symptoms.
ALPHA-1062 Shows Neuroprotective Effects in Preclinical Studies
The recently completed study, conducted in collaboration with the U.S. Department of Veterans Affairs and the Seattle Institute of Biomedical and Clinical Research, and supported by the U.S. Department of Defense, demonstrated that it has promising neuroprotective properties when administered after blast-induced mTBI.
Key Findings:
- Reduction in Toxic Brain Proteins: It significantly lowered levels of three toxic phosphorylated forms of Tau protein, which are commonly associated with both traumatic brain injury and Alzheimer’s disease:
- pTau 217: Known to identify individuals at higher risk of long-term cognitive decline after TBI.
- pTau S202/T205: Linked to very early Alzheimer’s pathology, present even before plaque and tangle formation.
- pTau 231: Elevated in early Alzheimer’s and associated with both neurodegeneration and TBI.
The observed reductions in these biomarkers suggest that ALPHA-1062 may reduce the risk of later developing Alzheimer’s disease in TBI-affected individuals.
Anti-Inflammatory and Neuroregenerative Mechanisms
Beyond reducing Tau pathology, ALPHA-1062 exhibited several additional beneficial effects relevant to brain repair and recovery post-injury.
Key Observations:
- Reduced Neuroinflammation:
- A decrease in myeloid cell counts, which are often elevated during neuroinflammatory responses.
- A reduction in astrocyte numbers, which may indicate a healthier brain environment as astrocytes play a key role in regulating neurotransmitters like glutamate and GABA.
- Increased Nerve Growth Factor Receptor Expression:
- This receptor plays a crucial role in neuronal survival and regeneration. Its dose-dependent increase with ALPHA-1062 treatment indicates a potential neurorestorative effect.
These outcomes align with results from a previous preclinical study in a moderate TBI model, further supporting the therapeutic promise of ALPHA-1062 across various severities of brain injury.
“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,”
— Dr. Denis Kay, Chief Scientific Officer, Alpha Cognition
Bridging Toward Clinical Application: Next Steps
Alpha Cognition is now preparing for the next phase of development, which involves advancing ALPHA-1062 toward human clinical trials. The immediate goals are:
- Formulating a sublingual (under-the-tongue) delivery system for ALPHA-1062, aimed at ensuring fast, reliable absorption without the need for injections or more invasive administration routes.
- Conducting a bridging pharmacokinetic study comparing:
- ALPHA-1062 sublingual formulation
- ZUNVEYL® (benzgalantamine), a current oral treatment used for neurodegenerative conditions
- An existing intranasal formulation of ALPHA-1062
These studies will help determine the most effective and patient-friendly delivery method and are essential for regulatory progression and eventual first-in-human trials.
A Broader Vision: Treating TBI and Preventing Neurodegeneration
The implications of these findings extend beyond mTBI. By targeting Tau-related neuropathology and neuroinflammation, ALPHA-1062 could have applications in preventing or slowing the progression of neurodegenerative diseases, especially in high-risk populations such as military veterans and contact-sport athletes.
With limited options currently available to treat TBI and its long-term consequences, ALPHA-1062 may represent a first-in-class therapeutic candidate with dual benefits: acute neuroprotection and long-term disease modification.
Conclusion
The positive preclinical results for ALPHA-1062 mark an important milestone in Alpha Cognition’s mission to develop novel treatments for neurodegenerative and brain injury-related conditions. Supported by leading military and research institutions, the company is now poised to bring this promising therapy closer to clinical evaluation.
By addressing both the immediate aftermath of mTBI and the long-term risk of dementia, ALPHA-1062 has the potential to significantly improve the lives of patients affected by traumatic brain injury—particularly those who have served in the military.
