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Trial to Test Engineered Amino Acid for Schizophrenia

Brain activity graphic

(Gordon Johnson, Pixabay)

2 Dec. 2019. A clinical trial plans to test a modified amino acid as an added treatment for schizophrenia that its developers say works differently than most current drugs. The trial is conducted by Concert Pharmaceuticals Inc. in Lexington, Massachusetts, testing its experimental therapy code-named CTP-692.

Schizophrenia is a common and chronic, yet severe and disabling disorder that affects up to 1 percent of the people in the U.S., but takes a wider toll on families and society. Symptoms of schizophrenia include hallucinations such as hearing voices, delusions, or agitated movements, as well as disrupted emotions and behavior affecting interactions, and causing lack of focus or loss of memory. Schizophrenia affects men and women, mainly adults, about equally and occurs at similar rates among ethnic groups around the world.

Concert Pharmaceuticals develops treatments for chronic diseases such as schizophrenia by altering the chemistry of therapies with the element deuterium. This element is an abundant and stable — i.e., non-radioactive — isotope of hydrogen that binds more strongly to carbon than hydrogen. The company says its technology substitutes deuterium for hydrogen in a compound’s chemistry, where deuterium can improve a drug’s therapeutic impact, safety, metabolism, or length of activity in the body.

CTP-692 is designed to treat symptoms of schizophrenia, as a supplemental drug given with current anti-psychotic medications. In CTP-692, Concert modifies with deuterium the chemistry of D-serine, an amino acid and neurotransmitter that activates N-methyl-D-aspartate or NMDA receptors in the brain. NMDA receptors are proteins that help keep synapses flexible, which affects memory, learning, and development of the central nervous system. People with schizophrenia often have low levels of D-serine, but modifications are needed to reduce potential toxicity to kidneys from D-serine in its natural state.

Most drugs for treating schizophrenia, says Concert, are designed to limit production of D2 receptors in the brain, proteins where overactive D2 receptor signaling triggers excessive production of the neurotransmitter dopamine. However, no therapies up to now address the low D-serine levels. “CTP-692 works through a different mechanism of action than existing anti-psychotic treatments,” says James Cassella, Concert’s chief development officer in a company statement, “and therefore offers the potential for broader symptom improvement when added to existing anti-psychotic treatments.”

The mid-stage clinical trial is enrolling 300 individuals with schizophrenia, being treated for the disease and with symptoms considered stable. However, recruitment has not yet started and the trial sites are not yet disclosed. Participants will be randomly assigned to receive 1, 2, or 4 grams of CTP-692, or a placebo, taken as oral drugs once a day along with their current anti-psychotic medications, for 12 weeks.

After 12 weeks, participants will be rated primarily on a standard Positive and Negative Syndrome Scale that measures the severity of schizophrenia symptoms. The study team is also measuring scores on another scale of schizophrenia symptoms and an index of social relationships, activities, and behaviors.

In October, Science & Enterprise reported on another clinical trial testing a drug addressing MNDA receptors, in this case a supplemental therapy for major depressive disorder. The trial, by Relmada Therapeutics in New York, shows improved scores on several symptom rating scales among participants taking the experimental drug.

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