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Experimental VBIT-4 Fights Alzheimer’s on Multiple Levels

Scientists at Ben-Gurion University developed VBIT-4, a small molecule for treating Alzheimer's disease that has shown remarkable success in mouse models.
Research lab

 Professor Shoshan-Barmatz has developed a small molecule, VBIT-4, that binds to VDAC1 and prevents the pathophysiological changes associated with Alzheimer’s. VBIT-4, a molecule that can cross the blood-brain barrier (BBB), was able to prevent the pathophysiological changes associated with Alzheimer’s disease, such as neuronal cell death, neuroinflammation and neuro-metabolic dysfunctions. Additionally, it also induced a neuroprotective phenotype in astrocytes and microglia, which are normally pro-inflammatory and neurotoxic.

Not only did the treatment protect against degeneration, it also promoted the healthy growth and normal functioning of neurons. Furthermore, the therapy also prevented decline of cognitive skills such as learning and memory in the mice.


Accumulated evidence points to an impairment of the metabolic mechanism in Alzheimer’s patients that develops several decades before the onset of dementia and deterioration of cognitive function.

Reduced metabolism results from a dysfunction of the mitochondria, which is responsible for producing most of the energy in the cell but is also involved in cell death, inflammation and immune response.

Despite the disease being linked to mitochondrial dysfunction, currently, no drug candidates have targeted this aspect. Researchers at Ben-Gurion University of the Negev are proposing a new treatment approach by targeting the mitochondrial gatekeeper, the voltage-dependent anion channel-1 (VDAC1), which controls mitochondrial activity and controls cell life and death.


The new proposed target and therapy demonstrated significant improvement across multiple parameters in mouse models, as reported in the prestigious journal Translational Neurodegeneration at the end of December 2022.

VDAC1 plays a crucial role in the cell death process mediated by mitochondria, which is why the team of researchers led by Prof. Varda Shoshan-Barmatz, with the participation of Prof. Shira Knafo, Prof. Alon Monsonego and Prof. Noga Vardi, a visiting professor from Pennsylvania University, along with a major contribution by Dr. Anna Kuzmin-Steinfer and Dr. Ankit Verma and others from Prof. Shoshan-Barmatz group chose to focus their efforts on the dysfunction of the mitochondria in a mouse model for Alzheimer’s disease as a target for treatment.

Prof. Shoshan-Barmatz’s research showed that an increase in the amount of the VDAC1 protein in the cell leads to its organization as a ring, with a large channel through which death-factor proteins and mitochondrial DNA exit, causing cell death and an immune response, respectively.

A high increase in VDAC1 levels has been found in heart diseases, intestinal diseases (Crohn’s), autoimmune diseases (lupus) and others. Here, the researchers show that the protein is produced in huge levels in the brain of a mouse model for Alzheimer’s disease and is concentrated in the nerve cells around the plaque.


Interestingly, the protective effects were achieved without significantly reducing Tau or amyloid (Aβ) plaques, which are commonly believed to be the main causes of Alzheimer’s.

This suggests that the Aβ-cascade hypothesis, which posits that these elements are the primary cause of the disease, may not accurately reflect the underlying cause of Alzheimer’s disease.

“Targeting VDAC1 with a novel molecule we developed presents an innovative approach to Alzheimer’s treatment, and can even be used as a preventive treatment,” said lead author Prof. Shoshan-Barmatz.


Ben Gurion University of the Negev


This research was funded by The Israel Science Foundation (Grant No. 974/19), and by a grant from the National Institute for Biotechnology in the Negev (NIBN).

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March 24, 2023 3:42 pm

So, are there clinical trials? If so, where? Or is this a readily available supplement or Rx people can try now since it’s proactive, rather than reactive to the onset of symptoms?

B. Berger
Reply to  Cheryl
March 27, 2023 12:46 pm

Best place to check is the U.S. government’s clinical trials site, .
Hope this helps.

Hanna Levi Julian

Hanna Levi Julian

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