Project Checklist

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Scientific Advisory Board April Planning Meeting
American Academy Of Neurology San Francisco,
CA April 25th, 2003
BRIGHT - Brain Injury Group, Hope through
Treatment
262-641-5639
www.brightonline.org
info_at_brightonline.org
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Page 1 - Agenda Hour 1

• Hour 1 - What can be done to help the children?
• Introduction of BRIGHT members and Advisory
  Board Members
• Brief summary of BRIGHT's Vision, Goals
  Objectives from a parent's perspective
• Brief summary of current state of knowledge,
  mechanisms of loss of function, mechanisms of
  recovery, (Matt to summarize, and send in
  advance, team to elaborate on during call)
• Discussion of disparity between parents
  wants/needs and 5-10 year achievable goals
  (technical disparity as well as economic
  disparity). What specifically is not currently
  being addressed?
• Summary - Three most promising areas to achieve
  parent's goals in 5-10 years

262-641-5639
www.brightonline.org
info_at_brightonline.org
3
Page 2 - Agenda Hour 2

• Hour 2 - How does the team organize itself to
  best help the children?
• Is there existing organizational
  capacity/interest to implement these solutions or
  does new capacity need to be created?
• What organizational structures would best allow
  the goals to be met? (i.e. parent advocacy group
  to generate interest and funding, a scientific
  workgroup to refine the science, and partner
  company to implement the rehab solution?)
• Can this current team provide all the skills to
  achieve the goal or do new members need to be
  recruited?
• Discuss detailed plan to organize - what will
  excite and motivate the group to work for our
  kids? (Form a Coalition? Form a new workgroup?
  Operate under the umbrella of BRIGHT? Governing
  structure?)
• Survey funding sources. (NIH, private
  foundations, corporate sponsors, direct
  fundraising)
• Action plan to secure funding. Who/What/When
• Summary - Define organizational strategy and
  who/what/when to secure funding.
• Next steps - Develop operating mechanism to
  monitor who/what/when. Set next teleconference
  date.

262-641-5639
www.brightonline.org
info_at_brightonline.org
4
Page 3 - Vision, Goals Objectives
Vision Goals and Objectives - From a parents
perspective...

• Mission and Population Served Our mission is to
  facilitate the organization and prioritization of
  resources around the goal of development and
  implementation of effective treatments for
  acquired brain injuries suffered in the fetal,
  neo-natal and the early childhood period. (I.e.
  primarily the Cerebral Palsy population)
• Vision Our vision is that our children will move
  and communicate successfully, allowing them their
  entitlement of a rich and full life.
• Objectives Our objectives are focused on the
  implementation of effective treatment strategies
  with-in the next 5-10 years such that our
  children will benefit.
• Full recovery of lost function for mild to
  moderate CP (GMFM Level 1-3)
• Attainment of enough function for improved
  quality of life for severe CP (GMFM Level 45)
• Improvement of cognition for types of CP where
  cognition is impacted

Our focus is organization and prioritization of
available resources for accelerated results
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Page 4 - What Is BRIGHT?
BRIGHTs Accomplishments to date...

• Received official 501(c)(3) status
• Developed a leadership core team with varied
  skill sets
• We have developed sources for operating funding
  including a
• letter writing campaign, on-line shopping,
  used car donation program, etc.
• Our website received over 300,000 hits in March
  alone
• provides information and resources for parents
  of brain injured children
• Our discussion groups provide support and
  guidance to both parents
• and practicing professionals, with over 4,000
  messages exchanged.

2003 focused on building BRIGHTs core
organization capacity
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Page 5 - Scope of the BRIGHTs Interest
BRIGHT believes an organizational capacity needs
to be developed that has expertise in all
physical processes affecting BI children...

• Neurological issues associated with the initial
  brain lesion
• Physical issues likely linked to the initial
  brain lesion, (I.e., sensory issues, muscle tone
  issues, Cortical Vision Impairment, GI issues,
  dysphagia, diaphragm weakness, etc.)
• Cognitive issues caused by the initial brain
  lesion
• Developmental issues caused by the secondary
  effects of the Brian Injury I.e.
• Development Disregard ala Ed Taub
• Maladaptive Plasticity ala Terry Sangers work
  with late onset dystonia
• Diminished myelinization because of reduced
  activity ala John McDonald
• W-sitting causing physical hip and knee issues,
  etc.

Does our current group have the expertise to
address all these areas We will revisit in Part
II of the call
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Page 6 - Current State of Knowledge
What is our current state of science and clinical
capability for these kids...
1.) Plasticity is seen as the key mechanism of
recovery for children with early brain injury

• Advances in neuro-imaging have shown that the
  brain is capable of plastically changing, using
  healthy areas to compensate for damage this is
  an major scientific paradigm shift (Nudo, 2000
  Xerri et al., 1998 Jenkins et al., 1990 Kaas et
  al., 1990)
• This concept can be Branded with the term
  Plasticity
• The concept of recovery of function through
  Plasticity has been demonstrated in both clinical
  interventions as well as in neuroscience
  research.
• Plasticity can be broadened to include the
  concept of both re-organization of the brain
  (I.e. training) as well as re-regeneration (I.e.
  Cell repair) of the brain through the re-wiring
  of new neural cells
• Re-generation (I.e. Cell repair) itself, will
  likely not result in improved function, ala Doug
  Kondziolka
• Re-organization (I.e. Training) itself, may not
  be enough in for recovery in some lesion types
  (I.e. Basal Ganglia) where the damaged cells are
  specialized and neighboring cells can not adapt?
  Is a combination of Re-generation and
  Re-organization needed for these kids?

Translating basic knowledge about brain
plasticity into solutions for children with
early brain injury
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Page 7 - Current State of Knowledge
What is our current state of science and clinical
capability for these kids...
2.) The brains development is influenced through
physical interaction with the environment

• Humans develop motor skill through a dynamical
  system approach. Motor development can be
  modeled as an open self organizing thermodynamic
  system. Changes in initial state (such as a
  brain injury, will have an effect on the
  resultant state of the system.) To some extend
  these changes should be predictable, and we in
  fact see them manifest themselves clinically
  (w-sitting, hip issues with Down Syndrome kids,
  etc.)
• Maladaptive plasticity can result in secondary
  issues beyond the effects of the initial brain
  injury
• Although the brain is capable of recovery, often
  little recovery occurs spontaneously this
  pattern is entirely predictable based on
  established principles of behavioral conditioning
  and has been given the term learned nonuse
  (Taub, 1994 Taub and Wolf, 1997 Le Vere, 1980)
• Maladaptive Plasticity ala Terry Sangers work
  with late onset dystonia
• Diminished myelinization because of reduced
  activity ala John McDonald
• W-sitting causing physical hip and knee issues,
  etc.

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Page 8 - Current State of Knowledge
Vicious Cycle ...
1996 - 1yr
2001 - 5yr
1999 - 3yr
Childhood Plasticity Can Be Advantageous and
Disadvantageous to Recovery Can We Break The
Vicious Cycle By Identifying and Treating the
Impairments?
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Page 9 - Current State of Knowledge
What is our current state of science and clinical
capability for these kids...
3.) Learning (plasticity) is facilitated during
Critical Periods,

• There are critical periods that learning is most
  efficient I.e Patching the good eye
• Can critical periods be expressed as periods of
  increased focal plasticity? Can critical periods
  be reproduced through techniques such as TMS or
  drugs?

4.) Effective measurements will be critical for
problem solving what tools are available

• Motor Growth Curves - can they provide
  statically significant data for small case
  studies
• fMRI - It as increased BOLD signal an effective
  surrogate marker for re-organization? Can we
  learn from fMRI?
• Movement Analysis - what can it tell us about
  motor learning?

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Page 10 - Current State of Knowledge
Motor Growth Curves

• Motor Growth Curves were on a large population
  of mixed CP kids in Canada over four years using
  the GMFM test.
• The curves appear to be predictive.
• The curves may serve as a control group against
  case studies can be measured.
• If a child is performing statistically better
  then the GMFMCS Group, can we conclude that the
  results are significant?

Prognosis for Gross Motor Function in Cerebral
Palsy Peter L. Rosenbaum, MD,FRCPC Stephen D.
Walter, PhD Steven E. Hanna, PhD Robert J.
Palisano, ScD Dianne J. Russell, MSc Parminder
Raina, PhD Ellen Wood, MD,FRCPC,MSc Doreen J.
Bartlett, PhD Barbara E. Galuppi, BA JAMA.
20022881357-1363.
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Page 11 - Current State of Knowledge
What is our current state of science and clinical
capability for these kids...
5.) Possible process for problem solving

• Can problem solving be done on a child by child
  basis and not in large multi-center clinical
  trails?

1.) Define goals 2.) Establish reliable
measurement system (both for Y's and x's) Y's re
outcomes as measured on the GMFM test. X's are
parameters like individual muscle strength,
motivation, speed of transmission of signal from
the nerve to the brain, temperament, number of
motor neurons recruited, mood, output of the
basal ganglia to the frontal lobe, etc. 3.)
Collect data (ideally in numerical form) 4.)
Analyze data (ideally sharing the data with a
large number of people) 5.) Identify the vital
few x's in the data (use techniques like
statistical analysis and Design Of Experiments to
achieve this) 6.) Develop experimental
techniques to address the vital few x's 7.)
Measure again 8.) Analyze the data again 9.)
Make corrections 10.) Ensure that the goals have
been met.
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Page 12 - Current State of Knowledge
What is our current state of science and clinical
capability for these kids...
6.) Possible treatment tools for improved function

• CIMT, Shaping, and massed practice - Functional
  gain through reorganization
• Robotic Assisted Therapy - Same mechanism as
  CIMT
• Artane - Impairment reduction pharmacologically
  for certain lesions (improves upper extremity
  movement )
• TMS - Can it selectively induce increased
  plasticity?
• Intense Activity - Can it induce neural
  generation? Reduce Spasticity?
• Strength Training - Can it reduce Spasticity?
• TheraTogs - Can this system provide stability
  and alignment and allow long term motor learning?
• Botox, Baclofen - Can it prevent contractures
  and result in improved long term motor learning?

Which treatment approach will result in
Improvements faster than the Motor Growth Curves?
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Page 13 - Short Term Focus
What is our current state of science and clinical
capability for these kids...

• Discussion of disparity between parents
  wants/needs and 5-10 year achievable goals
  (technical disparity as well as economic
  disparity). What specifically is not currently
  being addressed?
• Summary - Three most promising areas to achieve
  parent's goals in 5-10 years

What Three Specific Treatment Approaches Should
BRIGHT Focus
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Page 14 - Organizational Capacity
Do organizations exist that are trying to solve
this problem?

• No Specific NIH Focus
• United CP Research Foundation - Focus on
  causation prevention
• Movement Disorders Study Group
• Carter Foundation
• Childrens Neurological Solution - Focus on stem
  cells?
• ABC - AANs coalition
• ??

Does a GAP exist? Is a new organization needed?
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Page 15 - Organizational Structure
What structure would allow BRIGHT to meet the
goal of dramatically helping our children in 5-10
years?

• Parent advocacy group to generate interest and
  funding
• A scientific workgroup to refine the science
• Partner company to implement the rehab solution

What is needed?
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Page 16 - Current Team
Advisory Team
What Skills Need To Be Added To The Team?
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Page 17 - Motivations
What will excite and motivate you to work towards
BRIGHT goals?
How do we structure ourselves? What are our
Governing Rules? How do we disburse funds? Will
you get involved?
How do we structure ourselves?
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Page 18 - Funding
What are the existing funding sources? How
likely is it that we will be funded? To what
amounts? How long is the funding cycle?
NIH? Private Foundations? Corporate
Sponsors? Direct Fundraising?
What is our funding strategy?
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Page 19 - Action Plan For Funding

Who? What? When?
Action Plan
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Page 20 - Next Steps

• How will we measure success?
• How will we share information?
• How often will we meet?
• What is our next step?
• When will we have our next call?

Operational Mechanism