Stimulating Peripheral Activity to Relieve Conditions (SPARC)

Informational Webinar for RFA-RM-17-009

Technologies to Understand the Control of Organ Function by the Peripheral Nervous System

March 27, 2017

Features of NIH Common Fund Programs

Address important challenges/obstacles in biomedical research, and/or capitalize on emerging scientific opportunities where strategic investment can have an impact

Are catalytic: Programs must achieve a defined set of high impact goals within 5-10 years

Are goal-driven, with progress measured against concrete milestones

Promote the missions of multiple NIH Institutes and Centers (ICs)

Can require a high level of coordination

Each Common Fund program addresses unique scientific needs and opportunities, and so each program has a unique implementation plan driven by the science.

NIH Common Fund Programs

New Types of Clinical PartnershipsData/Tools/Methods

New ParadigmsTransformative Workforce Support

Illuminating the Druggable Genome

Glycoscience

Enhancing the Diversity of the NIH-Funded

Workforce

RegulatoryScience

Human Microbiome

Pioneer AwardsNew Innovator AwardsTransformative Research AwardsEarly Independence Awards

Genotype-Tissue

Expression

Library of Integrated Network-

Based Cellular Signatures

(LINCS)

Science ofBehaviorChange

Global Health

Big Data to Knowledge

(BD2K)

HCS ResearchCollaboratory

High-RiskResearch Common Fund

Health Economics

Epigenomics

Undiagnosed Diseases Network

Extracellular RNACommunication

Strengthening the Biomedical Research

Workforce 4D Nucleome

Gabriella Miller Kids First

Molecular Transducers of

Physical Activity in Humans

Metabolomics

SingleCell

Analysis

Knockout Mouse

Phenotyping

NIHCenter for

RegenerativeMedicine

Protein Capture

Stimulating PeripheralActivity to Relieve

Conditions (SPARC)

Recent FDA Market Approvals

Inspire EnteroMedics -Maestro

Medtronic - InterStim

BioControls - CardioFit MetaCure - Diamond

Boston Scientific - Vessix

Many randomized controlled trials miss their prespecified primary efficacy endpoints

Boston Scientific NECTAR Trial (Vagal Nerve Stimulation, Heart Failure)BioControls INOVATE Trial (Vagal Nerve Stimulation, Heart Failure)Medtronic SYMPLICITY (Renal Denervation, Hypertension) CVRx® Rheos (Baroreflex Activation Therapy)Apnex (Hypoglossal Nerve Stimulation, Sleep Apnea)St. Jude BROADEN Trial (DBS Area 25, Depression)Medtronic RECLAIM Trial (DBS Ventral Capsule/Ventral Striatum, Depression)Medtronic SANTE Trial (DBS ANT, Epilepsy)

Common Themes:followed successful open label studieslarge sham arm effectremarkable response in some patients

Autonomic Nervous System

Furness 2006

SPARC - Stimulating Peripheral Activity to Relieve Conditions

Opportunity: Neuromodulation of organ function holds promise in treating many diseases.

Challenge: The mechanisms of action for neuromodulation therapies remain poorly understood.

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.

~$238 million investment over 7 years

SPARC Components

SPARC1 Anatomical and Functional Mapping of the Innervation of Major Internal OrgansAnatomical and functional neural circuit maps for multiple major organsNovel electrode designs, surgical procedures, and stimulation protocols

SPARC2 Next Generation Tools and Technologies Novel and adapted technologies to define PNS control of organ functionNext generation neuromodulation therapies

SPARC3 Use of Existing Market-Approved Technology for New Market Indications New indications for existing, approved devicesNew therapeutic opportunities and methodologies

SPARC4 Data Resource Center (Data Coordination, Mapping, and Modeling)Public data resource containing SPARC dataIntegrated, predictive, anatomical, and functional neural circuit maps

SPARC Components

ANATOMICAL & FUNCTIONAL

MAPPING

NIDDKTRANSLATIONAL PARTNERSHIPS

NCATSDATA & RESOURCE

CENTER

NIBIB

TECHNOLOGY DEVELOPMENT

NIBIB/NINDS

SPARC Program Manager and Staff set overall vision and make adjustments

Other Transactionshttps://commonfund.nih.gov/sparc/OtherTransactions

Unique funding mechanism that is neither a grant, cooperative agreement, nor a contract

Funding Announcement

• Publication on the SPARC website and/or Grants.gov• Encourages nontraditional partners

Review

• Interactive discussion with Program staff• New reviewer voices• Selection of pieces of a proposal• Reviewer input considered by the SPARC Program Manager in

award selection

Award Management

Awarded activity can be:• Expanded• Modified• Partnered• Not supported• Discontinued

Based on: • Program needs• Emerging methods• Technologies or approaches• Availability of funds

SPARC TimelineM

APPI

NG

TOO

LSTR

ANSL

ATIO

NDA

TA

2015

3

New Tools (exploratory)

2016

22

Build public-private partnerships

2017

Maps 1.0

42

New tools (specific, need-driven)

“Next gen sharing”

2018

Leverage public-private partnerships for human functional mapping

47

2019

46

Maps 2.0

2020

42

2021

38

SPARC Snapshot, March 2017M

appi

ngTr

ansla

tion

Comprehensive (Shivkumar/UCLA)Auricular branch of vagus (Napadow/MGH)

Comprehensive (Bolser/U FL)Pulmonary neuroepithelial cells (Sun/UCSD)

Superior Cervical Ganglion(Lewis/Case Western)

Canning (Hopkins)/NuviantSynapse VNS for asthma

Comprehensive (Powley/Purdue)

Chen (Hopkins)/Boston SciSCS for gastric motility

Comprehensive (Howard/Toledo)Transcriptome (Southard-Smith/Vanderbilt)

Enteroendocrine cells (Shen/Duke)

Foundational maps (Keast/Melbourne)

ETC

Pancreas (Campbell-Thompson/U FL)Spleen (Campbell-Thompson/U FL)

Adipose tissue (Muenzberg-Gruening/Pennington; Zeltser/Columbia)

Yin (Transtimulation)/CVRxVNS for diabetes

Tool

s

Cardioneural mapping Electrodes (Ardell/UCLA)

Intrafascicular nanowire(Durand/Case)

Rabbit OSA model(Strohl/CWRU)

Ephys/IR mapping(Horn/Pitt)

Implantable gastric platform(Farajidavar/NYIT)

Ultrasound modulation(Okusa/UVA)

Mouse lines for ENS study(Howard/Toledo)

Human GI organoids(Wells/Cinncinnati)

Conformal bladder electronics(Gereau/WashU)

Bladder monitoring(Damaser/Cleveland Clinic)

Spinal root interface (Bruns/U Mich)

Viral bladder tools(Davis/Pitt)

Optical prove(Weir/U Colorado)

Viral tools(Vulchanova/UMN)

Data TBD TBD TBD TBD – APPLY!

SPARC1 – Neurocardiac CircuitryShivkumar – UCLA

Shivkumar group, UCLA Ardell et al 2016 J Physiol

SPARC2 – Miniature Multiphoton MicroscopeWeir – U Colorado

http://dx.doi.org/10.1364/OL.40.002553

Preliminary device

Cells in volume: > 200

Cells in volume: > 20049

0 μm

250 μm

Current design

Collaboration with Prof. Diego Restrepo, Department of Cell and Developmental Biology, Director Center of Neuroscience

SPARC2 – Funding Opportunities

Technologies to Understand the Control of Organ Function by the Peripheral Nervous System

• RFA-RM-17-009 (OT1, a.k.a. ”pre-application”)

• RFA-RM-17-010 (OT2, a.k.a. “application”)

• Quarterly OT1 receipt dates – first date is May 1, 2017

• Applicants whose OT1 pre-applications are found to be meritorious and programmatically relevant will be invited to submit a full OT2 application

• OT2 applications are invitation-only

Priorities

https://commonfund.nih.gov/sparc/FOAprioritiesVary for each OT1 receipt date

Posted online two months before each OT1 receipt date

May 1, 2017 PrioritiesImaging & Targeting

• Example: Fascicular tracing/targeting (biochemical, surgical, and/or viral)

Modeling & Simulation

• Example: Computational models to assess safety limits of stimulation and/or blocking of neural activity

Surgical • Example: Real-time in-vivo methods to determine if the PNS is damaged during surgery

Neural Interfacing

• Example: Biosensors to detect end-organ function biomarkers

Application Process

Discuss

• Optional, but encouraged discussion with SPARC program staff

OT1 application

• Email six-page OT1 application by receipt date in RFA-RM-17-009

• Must propose to address a Priority listed for this receipt date

Feedback

• We will provide feedback on your OT1 application

• Some applications will be invited to submit an OT2 application

Discuss

•Required discussion of feedback with SPARC program staff

OT2 app

•Invitation specifies deadline and other requirements

•Follow RFA-RM-17-010 to submit OT2 application to Grants.gov

Negotiate

•SPARC will negotiate budget, benchmarks, and deliverables with selected applicants

Award

•NIH will award an Other Transaction Award (OT2) after successful negotiation

OT1 Pre-application

This is not a typical NIH grant application

Cover Page (up to one page)Project Summary (up to one page)• Not a traditional Specific Aims page• Outline of project including objective, major tasks, milestones/benchmarks, timeline,

and deliverables. How do deliverable(s) address current SPARC Priorities?

Development Strategy (up to three pages)• Impact and Significance• Preliminary Data (not required)• Risk Analysis (optional for OT1)• Tasks, Benchmarks, Timeline, and Deliverables (go/no-go)• Key Personnel & Experience• Budget (high level)• Resource Sharing Plan

Bibliography (up to one page)

Evaluation

Innovation is not a scored criterion

SPARC uses objective review

Relevance and Justification

Benchmarks and Deliverables

Expertise

Resource Sharing Plans

NOT Responsive

Major deliverables which are not new technologies

Development of tools solely justified by a treatment or therapeutic strategy

Deliverables which are outside the SPARC Priorities for the receipt date

Study of organs in a diseased state

Tools and techniques to neuromodulate sensory organs of the head, named voluntary muscles, and the central nervous system above the spine

Data and Resource Sharing

Before applying, read the Material Sharing Policyhttps://go.usa.gov/xX8Hh

Funded projects will be required to make SPARC-developed technologies available to other projects in the consortium, and more broadly to the research community

Read the Funding Opportunity Announcements

SPARC is mission-drivenTools must facilitate mapping of peripheral nerve circuits

“Proposals must” vs. “proposals should”Ambiguity may be intentionalIs your concept in scope?Don’t work around restrictions

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Advice

Read the funding opportunityBe thorough

Analytical modelsExpected performanceCorner cases

Be specificBe quantitativeJustify

BudgetPeriod of PerformanceMission-relevance

Apis dorsata107.4 ± 13.2 mg unloaded5.4 m/s (from Apis mellifera)

17 mm ± 1 mm

hal.archives-ouvertes.fr/hal-00892251/document

Advice

Be clearWhat has been doneWhat will be doneWhat might be done

Deliverables & benchmarksDon’t distort realityDon’t whitewash risksDon’t waste pagesDon’t be late

Teaming

Multiple investigators are not a TeamIntegratePlan aheadFind weaknessesDebate tradeoffs

www.flickr.com/photos/124961070@N02/14485059353

ASK!

Talk to NIH staff before applying• Use proper channels• Visit http://nihsparc.setmore.com to sign up for virtual office hours• We strongly encourage applicants to discuss concepts with the SPARC team• We will provide feedback on program fit and suggestions on your concepts

aspiringmormonwomen.org/get-involved/

Office of the NIH Director TeamDr. Gene Civillico – Program Manager gene.civillico@nih.gov (301) 351-4180Dr. Felicia Qashu – Program Officer, OT Project Manager felicia.qashu@nih.gov (301) 451-7222Ms. Kristina Faulk – Communications Lead, OT Policy Analyst kfaulk@mail.nih.gov (301) 402-9185

Project Team LeadersBiology Dr. David Saslowsky: SPARC_Biology@mail.nih.gov (301) 594-8876

Dr. Patricia Greenwel: SPARC_Biology@mail.nih.gov (301) 435-1169

Technology Dr. Mike Wolfson: SPARC_NextGen-Tools@mail.nih.gov (301) 451-4778Dr. Andrew Weitz: SPARC_NextGen-Tools@mail.nih.gov (301) 451-4778

Translation Dr. Danilo Tagle: SPARC_New-Market@mail.nih.gov (301) 594-8064Dr. Siavash Vaziri: SPARC_New-Market@mail.nih.gov (301) 594-8921

Data Dr. Vinay Pai: SPARC_Data@mail.nih.gov (301) 451-4781Dr. Andrew Weitz: SPARC_Data@mail.nih.gov (301) 451-4778

SPARC Contacts and Resources

SPARC_NextGen-Tools@mail.nih.govSPARC2 Questions:

http://nihsparc.setmore.comVirtual Office Hours: