The ITN TCC’s goals and approach are described below.
The objective of the ITN TCC is to accelerate the introduction of new effective treatments for alcohol and substance abuse and comorbid disorders. The TCC program uses an integrated, multidisciplinary and multi-level approach. The TCC guides and accelerates the exploitation of the discoveries of the ITN Consortium by identifying the most promising pharmacological targets, validating their usefulness for treatment of SUDs and either supports or directly performs Phase II proof-of-principle human studies. This approach will both inform the design and improve the success rate of follow-on clinical trials. A second specific goal is to leverage ITN discoveries by attracting interest in pursuing full clinical trials from sources outside the ITN. Unique and innovative programmatic features of this proposal include: 1) explicit strategies to promote translation through regular meetings between human and animal researchers, 2) a Target Review Group that will meet frequently to select candidate medications that regulate the molecular targets identified by pre-clinical or human neurobiological studies as having near term promise of therapeutic efficacy, and 3) a Commercialization Group to coordinate consortium outreach to external entities to move promising treatments through to FDA approval. This program is unique in its specific focus on translation, its integration of human and animal neuroscience, and in its explicit investment in rapid movement of potential treatments to human proof-of-concept clinical studies. This approach has the potential to accelerate and reduce the risk and cost of development of new treatments for SUDs and comorbid disorders.
TCC Specific Aims
The TCC will promote integration and translation of pre-clinical and human neuroscience projects by accelerating the development of new treatments from pre-clinical to clinical studies. The specific aims are to:
1) Identify promising new pharmacotherapies by regular and systematic review of consortium investigators’ projects and proposals.
2) Provide current pre-clinical investigators with clinical assistance to test their hypotheses about disease mechanisms and/or to evaluate treatments suggested by their research.
3) Select, support and implement human investigations of disease mechanisms in individual substance abusers. Promote interactions between human and animal researchers to improve the design of small proof-of-concept human pharmacological studies.
4) Support and implement human and pre-clinical studies to investigate drug mechanisms (either abused or therapeutic) in individual substance abusers.
5) Reverse Translation:
a) Use human studies to validate animal models of substance abuse disorders.
b) Use discovery studies in human subjects to guide pre-clinical investigators. The program will encourage individual pre-clinical investigators to test hypotheses that emerge from human studies but that require invasive methods or the testing of drugs that have not been approved for human use. Ways in which human studies can inform animal studies include:
i) Genetic studies reveal unexpected associations leading to animal studies of the protein in question (e.g. COMT, 5HT2).
ii) Success with drug treatment promotes animal studies of relevant mechanisms and improved drug design.
iii) Functional imaging studies indicate brain areas and connectivity to be studied in animals using electrophysiology and pharmacology.