Initiatives to Support Research Activities for Translational Challenges in Neurology

Transcription

1 Initiatives to Support Research Activities for Translational Challenges in Neurology ASCP Annual Meeting June 1, 2017 Amir P. Tamiz, Ph.D. Associate Director, National Institute of Neurological Disorders and Stroke

2 Mission of NINDS To seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease Support and perform basic, translational, and clinical neuroscience research Fund and conduct research training and career development programs and ensure a vibrant, talented, and diverse work force Promotes the timely dissemination of scientific discoveries and their implications for neurological health to the public 27 different Institutes and Centers (ICs) 2

3 FY 2017 Appropriation Budget Distribution $69, % $54, % $1,783,654 $1,487, % $171, % FY 15 FY 16 DIR 159, ,878 RMS 63,894 67,050 Dollars in Thousands DIR RMS SBIR/STTR Extramural 3

4 NINDS Is Investing Across the Research Spectrum Basic Research FDA Review Diseasefocused research Target ID Assay Dev. High Thru-put Screen Pre- Clinical FDA IND IDE Ph. I Ph. II Ph. III Clinic 4

5 Promoting Basic Neuroscience Research 5

6 The BRAIN Initiative SM A focus on circuits and networks Measure the fluctuating electrical and chemical patterns within circuits Understand how all of this helps generate our unique thoughts and actions FY16 President s Budget request: $70M new FY16 BRAIN appropriation: $85M new 6

7 BRAIN Funding in FY2017: Opportunities 1. Short Courses: (MH ) 2. Novel Tools Cells and Circuits: (MH ) 3. Human Imaging: (MH ) 4. Human Invasive Devices: (NS /010/011/018) 5. Large-scale Recording & Modulation: (NS /007; EY ) 6. Invasive Neural Recording: (NS ) 7. Non-invasive Neuromodulation: (MH /815) 8. Technology Sharing and Propagation: (MH ) 9. Theories, Models, Methods: (EB ) 7

8 Investing Across the Translational Spectrum Grants Grants Translational Neural Devices Programs Dissemination and Implementation Research in Health (R01) Resources Contracts Training NeuroNEXT Clinical Trial (U01) StrokeNet Clinical trials & Biomarkers (X01) ADME/Tox. Chemistry Manufacturing Clinical Neurological Emergencies Treatment Trials (NETT) Preclinical and Early Clinical Trials Clinical Trials and Infrastructure Resource 8

9 Focusing on Early Translational Efforts PAR : Assay Development and Therapeutic Agent Identification and Characterization^ PAR : Pharmacodynamics and In vivo Efficacy Studies^ RFA-NS : Development and Validation of Translational Model Systems for Drug Discovery* 9

10 Adopting New Funding Models Infrastructure, Expertise, & Funding 10

11 Developing New Models for Clinical Research The NeuroNEXT program aims to: Provide a robust, standardized, and accessible infrastructure to conduct studies of treatments for neurological diseases Create and leverage partnerships with academia, private foundations, and industry Support scientifically sound, possibly biomarkerinformed, exploratory clinical trials clear go/no-go benchmarks Expand the pool of experienced clinical investigators and research staff 11

12 Improving Rigor in Science: An Expanding Dialogue NINDS efforts continue, led by Dr. Shai Silberberg, Director of Research Quality 1. Conversations within NIH: NINDS Rigor Working Group Evaluate impact of the new NIH rigor criteria Develop mechanisms that ensure the assessment of rigor in advance of significant NINDS investments 2. Conversations with broader community: Scientific/professional societies to increase transparency at meetings Journal editors to develop recommendations for minimizing publication bias Develop and disseminate training materials Focus Areas Scientific Premise Scientific Rigor (Design) Biological Variables Authentication 12

13 Training in Neurotherapeutics Discovery & Development NIH Blueprint for Neuroscience Research Short Course for Academic Neuroscientists 1. Explores various topics critical to discovery and development of neurotherapeutic agents 2. Provides individualized mentoring and assessment 3. Provides opportunities to interact with topic experts Over 100 people have participated to date Representation from 53 unique institutions/universities Disease area representation from 6 NIH institutes 13

14 Increasing Diversity 14

15 Advancing Fundamental Knowledge Brain & Nervous System Funding At least partial NINDS or NIH support Suvorexant for Insomnia Other Narcoleptic patients have profound decrease in CSF Orexin Both Orexin receptors are required for wakefulness FDA approves Suvorexant for insomnia Discovery of Orexin peptide and receptor family Canine narcolepsy caused by mutations in Orexin receptors Dirunal variation of CSF Orexin levels in humans Dual orexin receptor antagonist (suvorexant) induces sleep in rats, dogs, humans Clinical trials demonstrate safety and efficacy of Suvorexant 2000s 2010s 15

16 Support Basic & Translational Activities NINDS Support for Familial Dysautonomia Research Kinetin Discovered Kinetin Analogs at NIHCGC PTC partnership Locus Discovered Gene Discovered Tg Mouse Model Developed BPN Project NINDS P01 Breakefield NINDS R01 Gusella/Slaugenhaupt NINDS R21 Slaugenhaupt NINDS U01 Slaugenhaupt NIH/NINDS has supported Slaugenhaupt from Post-doc to Full Professor 16

17 NIH Application & Review Process Applicant initiates research idea Applicant Identifies the appropriate program announcement Program Staff Submits grant application to NIH electronically era/grants.gov Helpdesk NIH Center for Scientific Review assigns to IC and IRG Referral Office IC staff prepare funding plan for IC Director Program Staff Grants Management Advisory Council or Board recommend Approval Program Staff Scientific Review Group evaluates scientific merit Scientific Review Officer IC allocates funds Grantee conducts research 17

18 NIH Application & Review Process Applicant initiates research idea Applicant Identifies the appropriate program announcement Submits grant application to NIH electronically NIH Center for Scientific Review assigns to IC and IRG 1-2 Months 3 Months 2-4 Months IC staff prepare funding plan for IC Director Advisory Council or Board recommend Approval Scientific Review Group evaluates scientific merit IC allocates funds Grantee conducts research 18

19 Amir Tamiz,

20 21 st Century Cures Establishes the Beau Biden Cancer Moonshot & NIH Innovation Account in the treasury. It authorizes $4.8 billion over 10 years to be transferred into this account to carry out: Cancer research = $1.8 billion over 7 years Precision Medicine Initiative = $1.455 billion over 10 years BRAIN Initiative $1.511 billion over 10 years Regenerative Medicine = $30 million over 4 years Amounts must be appropriated each year, are available until expended, and will not count against the budget caps Also includes FDA provisions and funding for mental health and opioids treatment and services 20

21 SPARC - Stimulating Peripheral Activity to Relieve Conditions Mission: Catalyze rational target development for peripheral neuromodulation indications of scientific and clinical importance by building anatomical and functional maps of the innervation of major organs MAPS Program Goals: Provide a scientific foundation that enables better understanding of the neural control of organ function, spurring development of the next-generation of therapeutic closed-loop neuromodulation devices. TOOLS TRANSLATION DATA An NIH Common Fund Program ~$238 million investment over 7 years 21