Can anle138b delay the onset of genetic prion disease?

Sonia Vallabh & Eric Minikel

Massachusetts General Hospital

$17,217Pledged
215%Funded
$16,800Next Goal
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This project was funded on:
28 September 2013
Prions - infectious proteins - cause fatal, untreatable neurodegenerative diseases. A promising new compound looks like it may be able to delay onset. Will it work against genetic forms of the disease?

Update: we have now raised funding to study this compound in three models of prion disease including a model of Sonia's own mutation, fatal familial insomnia. On our last day we are now fundraising to support our many other projects, described below.

What are the goals of this project?

This project will determine whether anle138b can delay the onset of symptoms and extend survival in a mouse model of A117V Gerstmann-Straussler-Scheinker syndrome, a genetic prion disease.

update: We have now announced a study design and budget for studies of this compound in mouse models of fatal familial insomnia (FFI) caused by the D178N 129M mutation, and Creutzfeldt-Jakob disease (CJD) caused by the E200K mutation. Together with the original GSS project, these studies will determine whether anle138b is effective against a range of different genetic mutations that cause prion disease.

update #2: We have now met all three goals! In our final day we will raise funds toward our many other research goals. We want to understand how prion protein is regulated in the cell, use gene silencing approaches to reduce it, develop new assays, investigate other potential drug candidates, and much more!


Why is this research important?

anle138b is the most promising anti-prion compound yet discovered, but to date it has only been tested in vivo against one prion strain. This project will determine its efficacy against an entirely different strain of prions, in a model that closely mimics the pathology of a human prion disease.

Prion diseases are extremely rapid, with mortality following only months after initial symptoms. However, many carriers of genetic prion diseases - including us - have undergone predictive genetic testing and know their status decades before the onset of any symptoms. Genetic prion diseases provide an opportunity for early intervention and a potentially large therapeutic effect.

How will the funds be used?

Funds for this project will be spent on mouse space, labor and equipment for a therapeutic trial in GSS mice at Dr. James Mastrianni's facility at University of Chicago. The experimental compound anle138b will be provided for free by the drug's inventors, Dr. Armin Giese and Dr. Christian Griesinger.

update: Funds raised beyond our original goal will go towards trials of anle138b against fatal familial insomnia and E200K Creutzfeldt-Jakob disease led by Dr. George Carlson at McLaughlin Research Institute. A detailed budget for these additional studies can be found in this blog post. Each study will cost $4,400 and they are represented by Goal 2 and Goal 3 above.

Budget

Budget Overview

The total cost of this study is $16,013. Prion Alliance has funded half of the project costs up front, and the other half is being raised through this Microryza project. Dr. Armin Giese has provided the experimental compound anle138b at no charge.

As shown in the budget breakdown, funds will be spent on labor costs, mouse space and laboratory supplies.

The detailed budget breakdown for our additional two goals of $4400 each can be found in this blog post.

Meet the Researcher

Background

We learned in December 2011 that Sonia carries the D178N 129M mutation that causes fatal familial insomnia, a genetic prion disease. Since then, we've launched a personal quest to cure prion diseases. We changed our careers to become scientists, started a scientific blog, CureFFI.org and a non-profit research foundation, Prion Alliance.
Our collaborators for this project have been in this field much longer. Dr. James Mastrianni at University of Chicago, as both a neurologist and a researcher, studies the pathogenesis of prion diseases from the molecular level to the clinic. He is an expert on genetic prion diseases and developed the GSS mouse model that we will use in this study and has conducted previous therapeutic trials using this model. Dr. Armin Giese at Ludwig Maximilian University of Munich has studied the biochemistry and cell biology of prions for two decades. For the past ten years he has led high-throughput screening and lead development efforts for anti-prion compounds, culminating in the recent invention of anle138b.


Video produced and directed by: Chelsea Groves Kuhnle & Alan Ransil.

Background image of cultured neurons: Randy Singh Atwal.

Anle138b citations: U.S. Patent US20110293520, Wagner 2013. See also our review of prion therapeutics tested in vivo.

Mouse model citations: GSS A117V Yang 2009; see also previous therapeutic study of rapamycin using this model, Cortes 2012. Fatal familial insomnia Jackson 2009, E200K Creutzfeldt-Jakob disease Jackson 2013.

The genetic prion diseases include fatal familial insomnia (FFI), Gerstmann-Straussler-Scheinker syndrome (GSS) and the genetic forms of Creutzfeldt-Jakob Disease (CJD). For a review see Mastrianni 2010 (full text here). For some lighter reading see also our introduction to fatal familial insomnia.

Project Backers

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