Science

The neurotransmitter dopamine underlies the brain’s exquisitely precise regulation of physical movement. The neurotransmitter glutamate accounts for more than 80% of the brain’s activity. Restoring dopamine and glutamate balance is the key to reducing symptoms and improving health and well-being for many people with serious neuropsychiatric conditions.

Tourette Syndrome

Children and adults with Tourette Syndrome experience involuntary repetitive movements and vocalize sounds or words that they cannot control, and often struggle with other serious neuropsychiatric conditions.

Autism Spectrum Disorder

Children and adults with Autism Spectrum Disorder may struggle with social interactions, learning and communicating, become easily overwhelmed, and get stuck in loops of behavior or thinking.

Traumatic Brain Injury

There are more than 250,000 hospitalizations and 55,000 deaths a year in the US alone due to head injury, potentially leading to a wide range of long-term or neurological disabilities. Excess glutamate may play a major role in causing neuronal damage.

Other indications

EuMentis is evaluating other neuropsychiatric conditions that involve glutamate or dopamine imbalance for low-trapping NMDA antagonists, EM-221, or other novel compounds derived from its platforms.

EM-221, a PDE10A Inhibitor

EM-221 precisely modulates dopaminergic brain circuits that are believed to cause the unwanted movements and vocalizations in children and adults with Tourette Syndrome. Because its mechanism of action is highly specific to the brain’s movement centers, it is expected to be much safer than antipsychotics, which are approved and effective but have serious and sometimes long-term side effects.

How EM-221 works for Tourette Syndrome

GPe = globus pallidus externus
STN == subthalamic nucleus
GPi = globus pallidus internus
SNc = substantia nigra pars compacta

Brain Circuits

Tourette syndrome is believed to be caused by overactive neuronal pathways that generate tics in the parts of the brain that regulate and coordinate motor movement and speech, including the basal ganglia and its connecting circuits.

In the Striatum

Inside the neuron, the PDE10A enzyme normally breaks down cAMP, reducing their levels inside the cell. EM-221 inhibits this enzyme, increasing levels of cAMP inside the cell. The overall effect is to increase inhibition of neuronal signaling via the dopamine indirect pathways, restoring normal balance in the regulation of movement.

Noncompetitive low-trapping NMDA antagonists

EuMentis is developing noncompetitive, low-trapping glutamate antagonists designed to inhibit receptors on neurons that are overly active. EuMentis is combining this clinically-validated approach with novel imaging technology to identify patients with autism spectrum disorder who are most likely to benefit.

Autism Spectrum Disorder

So far, there are no approved medications for this condition, although an imbalance in regulation of brain glutamate may underly ASD. A low-trapping NMDA antagonist can restore glutamate equilibrium without causing new and serious side effects.

See how an NMDA antagonist can work for Autism Spectrum Disorder

NMDA antagonists block signaling of over-active glutamate receptors

Traumatic Brain Injury (TBI)

Excess glutamate released after traumatic brain injury can lead to further damage and death to exposed neurons. There are no approved medications for TBI. EuMentis is working to identify an NMDA antagonist treatment to accelerate recovery and reduce long-term disability, funded by a grant from the US Department of Defense.

Product

Discovery

Preclinical

Phase 1

Phase 2

Phase 3

Pivotal Study

EM-221

Tourette Syndrome

EM-221

Tourette Syndrome

Discovery

Preclinical

Phase 1

Phase 2

EM-221

For other CNS indications

EM-221

For other CNS indications

Discovery

Preclinical

Phase 1

Phase 2

EM-113

For autism spectrum disorder

EM-113

For autism spectrum disorder

Discovery

Preclinical

Phase 1

Phase 2

NMDA Antagonist

For traumatic brain injury

NMDA Antagonist

For traumatic brain injury

Discovery

Preclinical

Phase 1

Phase 2

NMDA Antagonist

For other CNS indications

NMDA Antagonist

For other CNS indications

Discovery

Preclinical

Phase 1

Phase 2

EM-113 Study explore our approach

Science

Tourette Syndrome

Autism Spectrum Disorder

Traumatic Brain Injury

Other indications

EM-221, a PDE10A Inhibitor

How EM-221 works for Tourette Syndrome

Brain Circuits

In the Striatum

Noncompetitive low-trapping NMDA antagonists

Autism Spectrum Disorder

Traumatic Brain Injury (TBI)

EuMentis Product Pipeline