Pharmacogenetic treatment of psychiatric symptoms through L-proline transport inhibitors

This technology is a diagnosis and treatment for patients with psychiatric disorders that can also be used to predict response to treatment with an L-proline transport inhibitor.

Unmet Need: Effective treatment for schizophrenia and bipolar negative symptoms

Proline neuromodulators such as LX6171 have been proposed as potentially promising therapeutics to treat negative symptoms associated with psychiatric conditions such as schizophrenia, bipolar disorder, and anxiety disorders. LX6171 is an inhibitor of SLC6A7, a solute carrying protein of the GABA neurotransmitter transporter family, and has been proven safe in clinical trials. However, patient response to such drugs is largely dependent on their catechol-O-methyltransferase (COMT) enzyme genotype. Negative symptom episodes may increase or decrease in response to agents that increase circulating proline levels, depending on the patient’s COMT genotype. A method to predict patient response to proline neuromodulators is needed.

The Technology: Pharmacogenetic response prediction for proline neuromodulators in the treatment of psychiatric disorders

This technology assesses a patient’s COMT genotype to determine if treatment with an L-proline transport inhibitor that target solute carriers, such as LX6171, would be beneficial. In particular, patients with the Val/Val COMT genotype have been shown to exhibit lower negative symptoms when they have higher circulating proline. As such, proline transport inhibitors that target solute carriers like SLC6A7, which can increase proline levels at the synapse, may be especially beneficial for this subpopulation of patients. This assay can enable safer, targeted, and more effective treatment of negative symptoms in psychiatric disorders.

Applications:

• Diagnostic assay to inform the treatment of psychiatric patients with negative symptoms
• Pharmacogenetics assay to predict patient response to agents that affect proline levels
• Treatment for negative symptoms of schizophrenia or bipolar disorder
• Research tool for analysis of drug metabolism and COMT enzyme

Advantages:

• Increases the probability of administering an effective treatment
• Enables the effective treatment of negative symptoms of psychiatric disorders
• Improves safety of proline-modulating treatments
• Can reduce the incidence of unwanted and potentially harmful side effects

Lead Inventor:

Catherine L. Clelland, Ph.D.

Patent Information:

Patent Status

Related Publications:

• Clelland CL, Drouet V, Rilett KC, Smeed JA, Nadrich RH, Rajparia A, Read LL, Clelland JD. “Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder” Transl Psychiatry. 2016 Sep; 6(9): e891.

Tech Ventures Reference:

• IR CU17320

• Licensing Contact: Kristin Neuman