Catatonia is a widespread and serious syndrome characterized by mutism, stupor, refusal to eat or drink, posturing, and hypokinesis, and affects a broad range of psychiatric and other patients in the US and worldwide. Untreated or poorly managed catatonic patients suffer from a wide range of ailments including bed sores, deep venous thrombi, pulmonary emboli, urinary retention, infection, and aspiration pneumonia, which can lead to severe medical impairment and death. Existing treatments for catatonia including lorazepam (a benzodiazepine) often require high doses for an effective response, some patients are unresponsive, and chronic catatonia is poorly controlled. Discovery of a new treatment for catatonia would have a considerable commercial and scientific value. Our approach is to target an orphan drug receptor present in the cerebellum that is preferentially activated by lorazepam. We propose to carry out a Structure-Activity Relationship (SAR) program of synthesis and biological evaluation of specifically designed lorazepam derivatives. From this project we specifically aim to discover one or more benzodiazepine analogs showing the desired in vitro orphan drug receptor potency and selectivity. In Phase Two compounds with a promising in vitro profile will be examined in vivo in knockout mice to confirm their mode of action. The best lead compounds will be further optimized and then evaluated in an animal model for catatonia. The long- term goal of this project is to discover a new, improved pharmaceutical agent for treatment of catatonia that can be licensed and developed for ultimate market approval.

Public Health Relevance

Catatonia is a serious health problem in the Unites States, and the existing drug treatments are not always effective and have side effects. We are carrying out research to discover and develop a new drug to help these patients. If we are successful, doctors will have another option to help sufferers of catatonia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
5R43MH095315-02
Application #
8333938
Study Section
Special Emphasis Panel (ZRG1-IMST-K (11))
Program Officer
Grabb, Margaret C
Project Start
2011-09-16
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$331,270
Indirect Cost
Name
Organix, Inc.
Department
Type
DUNS #
161843057
City
Woburn
State
MA
Country
United States
Zip Code
01801