Proposal for Autism & GI  Pilot Studies

Goals:

• Use existing infrastructure to quickly evaluate data to support or reject narrow /specific hypotheses related to autism.
• Broadly study tissue that appears relevant in autism (GI samples) to generate new hypotheses.
• Positive data would serve as foundation for larger studies / grant proposals.
• Positive data could translate into support for use and study of therapeutics already on the market.
  • Reasons these therapeutics have not been studied to date: Very expensive ($15k / year ) and IRB issues.

Observations:

• Arthur Krigsman and others have identified a new disease entity: autistic enterocolitis
• Large number of autistic children affected
• Host of chronic GI problems
• Pathology observed upon biopsy

Question:

• What factors are responsible for the observed symptoms / underlying pathology?
• How can we facilitate development of effective treatment modalities?

Proposed Experimental Approaches:

Collect ileocolonic biopsy tissue from a number of affected and unaffected children (already underway, multiple samples banked, and IRB in order):

• Isolate RNA and measure gene expression: compare autistic (pathologic) profile to controls.
  • This will define a molecular biological signature with which to compare autism patients. Currently autism is defined clinically and this is inadequate. It is akin to stating that a patient has “back pain.” That is not informative as it could be caused by something as benign as muscle strain or as serious as cancer.
• Measure viral RNA levels

Culture biopsy tissue (primary cell culture – can be maintained for up to 8 days without differentiation from their original phenotype):

• Measure basal gene expression
• Measure  protein expression (e.g. cytokines)
• Measure viral RNA levels
• Challenge cells with, e.g. TNF-α, then measure response

Expectations:

Within six to twelve months, we will have:

• Extensive data on molecular biological patterns unique to autism GI tissue
• Extensive data on whether any number of viruses can be found in autism GI tissue
• Data on go / no go supporting decision to use TNF inhibitors (already on the market) in clinical trial

People:

• Arthur Krigsman, M.D.
• Steve Walker, Ph.D.
• Other support staff at Wake Forest Medical School
• Jeffrey Segal, M.D.
• Consultants (e.g. Andrew Wakefield, Jeff Bradstreet, Jane El-Dahr,)

Management / Oversight:

• Process will be data driven
• Process will be cost effective- with follow up projects supported only if specific milestones are met.
• Process will be multidisciplinary- exploiting core competences of those with different skill sets.

Funding Requirements:

The proposed budget is $150,000 – 200,000 for these pilot studies. These funds will allow us to collect data sufficient for a more substantial and sustained funding from the NIH.

To donate specifically to this study, click here.