Blarcamesine, also known as ANAVEX 2-73, is an investigational small molecule drug. Developed by Anavex Life Sciences, it is being explored as a potential oral treatment for various neurodegenerative and neurodevelopmental disorders.
How Blarcamesine Interacts with the Body
Blarcamesine primarily functions as an activator of the sigma-1 receptor (S1R). The sigma-1 receptor is a chaperone protein located mainly on the membranes of mitochondria-associated endoplasmic reticulum. This receptor plays a significant role in maintaining cellular balance, particularly within neurons.
When blarcamesine activates the sigma-1 receptor, it helps to restore normal function to cells that are experiencing damage or stress. This activation can influence several cellular processes, including protein folding, the cellular stress response, and the survival of neurons. It can also help to reduce oxidative stress and programmed cell death, known as apoptosis. Furthermore, blarcamesine interacts with muscarinic acetylcholine M1 receptors and, to a lesser extent, ionotropic glutamate NMDA receptors, which are involved in memory formation and neurotransmission.
Investigating Blarcamesine for Neurological Conditions
Blarcamesine is being primarily investigated for its potential application in Alzheimer’s disease. The rationale for its use in this context stems from its ability to influence multiple pathological pathways associated with the disease. This includes addressing neuroinflammation, mitochondrial dysfunction, and the misfolding of proteins that contribute to the formation of amyloid-beta plaques and tau tangles.
Beyond Alzheimer’s disease, blarcamesine is also being investigated for other neurodegenerative and neurodevelopmental conditions. It is in various stages of clinical trials for disorders such as fragile X syndrome, Rett syndrome, Parkinson’s disease, and Angelman syndrome. Development for conditions like amyotrophic lateral sclerosis (ALS), anxiety, and multiple sclerosis has been discontinued.
The Journey Through Clinical Trials
Blarcamesine has progressed through several phases of clinical trials for neurodegenerative conditions. It has successfully completed Phase 2a and Phase 2b/3 clinical trials for Alzheimer’s disease.
As of August 2024, blarcamesine is in preregistration for Alzheimer’s disease, indicating it is nearing the stage for potential regulatory review. It is also undergoing Phase 2/3 clinical trials for fragile X syndrome and Rett syndrome, Phase 2 trials for Parkinson’s disease, and Phase 1 trials for Angelman syndrome and infantile spasms. Recent data from a Phase 2b/3 study in early Alzheimer’s disease, presented at the 2024 Alzheimer’s Association International Conference, showed that blarcamesine slowed cognitive decline and exhibited a manageable safety profile. Anavex Life Sciences intends to submit a full regulatory application for blarcamesine in Europe by the fourth quarter of 2024.
What Blarcamesine Could Mean for Patients
If blarcamesine continues to demonstrate positive results, it could influence the course of neurodegenerative conditions like Alzheimer’s disease. Studies have observed that treatment with blarcamesine may slow cognitive worsening. For instance, one study reported a significant slowing of cognitive decline by 34.6% at the 30 mg dose and by 38.5% at the 50 mg dose compared with a placebo group.
Blarcamesine has also been associated with a reduction in brain atrophy, which signifies the loss of nerve cells. Observed reductions included a 37.6% decrease in whole brain atrophy, a 63.5% decrease in total gray matter atrophy, and a 25.1% decrease in lateral ventricle atrophy. The drug’s safety profile has been well-tolerated across trials. The most frequently reported effect has been dizziness, which was often transient and manageable, sometimes through adjustments in the dosing schedule.