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Treating Neurodegenerative Diseases with Dihexa

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Neurodegenerative diseases are characterized by progressive neuron losses in specific brain regions that impact cognitive, sensory, and motor functioning. These disorders include Alzheimer’s disease (AD), Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. The destructive nature of the damage inflicted by these diseases results in a loss of patient dignity and self-worth and negatively impacts family members and friends. 

What is Dihexa?

N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (Dihexa), a potent cognitive-enhancing molecule that proved to be very stable, capable of inducing spinogenesis/synaptogenesis at picomolar concentrations, slowly cleared from the blood compartment, and sufficiently BBB-permeable.

Dihexa is a first-in-class compound that is orally active, penetrates the blood-brain barrier, and facilitates memory consolidation and retrieval. This angiotensin-based small molecule may be efficacious as a treatment for neurodegenerative diseases. 

How can Dihexa help those suffering from Neurodegenerative disease?

The therapeutic value of this approach lies in its capacity to encourage the formation of new functional synaptic connections among existing neurons, encourage the replacement of damaged and lost neurons from available neural stem cell populations, and facilitate cerebral blood flow and neuroprotection. Such treatment outcomes would benefit patients afflicted with AD and possibly those suffering from other neurodegenerative diseases.

This small molecule was derived from the pre-prototype molecule Nle1-angiotensin IV. It has shown promise in facilitating the formation of new functional synaptic connections and augmenting memory consolidation.

The pharmacokinetic limitations of metabolic instability and an inability to pass the blood-brain barrier have recently been overcome by the design and synthesis of Dihexa, a novel AngIV analog. Dihexa has documented procognitive/antidementia activity, is metabolically stable, blood-brain barrier–permeant, and orally active (McCoy et al., 2013).

The consistent ability of an augmented HGF/c-Met system to support synaptic plasticity and reverse nervous system deficits.


• The brain angiotensin system now includes learning, memory, and motor functions.

• Antidementia properties. 

• Cognitive enhancement and increased mental stamina.

• Heighten creative thinking, social intuition, and conversational skills.

• The AngIV/AT4 receptor system coincides with the HGF/c-Met receptor system.

• Improve focus and learning.

• Dihexa binds at HGF and facilitates dimerization and availability at c-Met receptors.

• Activation of the c-Met receptor increases hippocampal synaptic connectivity.