The Action

List of Projects Funded by Nash Avery Foundation

A.T. Still University of Health Sciences — Dr. George Carlson

Anti-Inflammatory Agents

Dr. Carlson is evaluating the utility of anti-inflammatory agents that prevent muscle cell death as potential treatments for DMD. Two of the drugs he is testing are currently in widespread use for other illnesses. Research indicates that they inhibit the NFkB pathway, an intervention that should have clinical benefit for boys with DMD. Dr. Carlson is administering the drugs to mice with muscular dystrophy and evaluating functional improvement.

BioFocus DPI — Netherlands

Utropin Assay Development

Dr. Fischer’s team is developing a highly sensitive assay to measure expression of the protein utrophin in human muscle cells. Increasing production of utrophin can compensate for the absence of dystrophin in DMD patients. The high-through put assay will allow for the screening of potentially useful drugs.

Brown University — Justin Fallon, PhD

Biglycan — novel biotherapeutic

Utrophin is a compensatory protein that can act as a substitute for dystrophin, the missing protein in DMD boys. Dr. Fallon has discovered that a protein called biglycan can upregulate utrophin expression in a muscular dystrophy mouse model. He has observed other beneficial effects of biglycan, including reduction of muscle fiber cell death. In Dr. Fallon’s previous studies, a single dose of biglycan was effective in the mouse model for three weeks. Dr. Fallon is currently testing biglycan in the mouse model to determine whether mice treated with biglycan show functional improvement.

Children’s National Medical Center — Dr. Kanneboyina Nagaraju

Testing supplements and pre-approved drugs in a mouse model

Dr. Nagaraju is investigating four experimental drugs (Celastrol, Resveratrol, Lipoxin A, Cyclosporine A analog) that may prevent muscle degenaeration and increase muscle function. This project tests these drugs in the DMD mouse model, so we can determine whether human clinical trials are warranted.

Columbus Children’s Research Institute — Paul Martin, PhD

Galgt2 assay developement

From previous studies, Dr. Martin concluded that Galgt2, a protein that adds sugar to other proteins, could be a therapeutic target for a treatment for DMD. Mice with muscular dystrophy have a 3-fold increase in natural expression of Galgt2. This observation led Dr. Martin to conclude that Galgt2 overexpression may ameliorate the dystrophic condition. Dr. Martin is now developing a reporter cell line that can be used to screen compounds that would activate the human Galgt2 promoter, thereby causing overexpression of the protein.

DMDeTank — Worldwide

Assay Development

Charley’s Fund has initiated an innovative project that taps the global scientific community to solve problems facing DMD researchers. Collaborating with InnoCentive, a web based company that matches top scientists from around the globe with relevant R&D challenges, we have compiled a “virtual” think tank of DMD and drug development experts.

The e-Tank is:

Project Catalyst—South Plainfield, NJ

Small Molecule Therapy

Project Catalyst is a targeted research program designed to develop oral medications that can delay muscle degeneration in DMD. The research is being conducted by PTC Therapeutics, a New Jersey biotech firm that currently has a DMD drug in Phase II human clinical trials. This drug, called PTC 124, will benefit 10-15% of boys with DMD who have a particular genetic mutation called a “stop codon” or “nonsense mutation.” PTC is now selecting additional drug candidates that will help the remaining 85% of children with DMD. They expect to begin preparations for human clinical trials for at least one more drug by April 2008.

CombinatoRx — Cambridge, MA

FDA Approved Drugs

This Massachusetts based company looks for cooperative synergistic effects when two drugs are used in combination. CombinatoRx screens for already approved drugs that have gone through the FDA approval process for other diseases amd will test each individual drug and in combination to determine if any existing may be useful for DMD boys. If succesful, this is the fastest way to get new drugs to this generation of boys.

Summit plc (formerly VASTox plc) — United Kingdom

Utrophin Upregulation

A UK-based biotechnology company, Summit plc is searching for new drugs that will increase expression of the protein utrophin. We teamed up with the Nash Avery Foundation to pay for Summit to purchase a library of 30,000 compounds so they can expand their search. Utrophin can compensate for dystrophin, the missing protein in DMD boys.

University of Colorado — Brian Tseng, MD, PhD

Molecular Sealant

Dr. Tseng is developing a “molecular sealant” to patch the holes in the muscles cells of boys with DMD and strengthen the membranes. The sealant, called Poloxamer 407, is approved for use in commonly used mouthwashes and drugs. It is currently undergoing human clinical trials for other diseases. Together with Charley’s Fund, this effort is being supported by the Nash Avery Foundation, the Jett Foundation and Cure Duchenne.

University of Minesota — James Ervasti, PhD


Dr. Ervasti has come up with a way to transport utrophin -- a protein that can act as a substitute for dystrophin -- to the muscle cells. This approach requires that utrophin is attached to another protein called TAT. This new fused protein (or chimera) is then transported into the cell. Dr. Ervasti has promising preliminary results that demonstrate improvement in a mouse model treated with this therapy. Currently, Dr. Ervasti is investigating the chimera’s optimal dosage, frequency of administration, and mode of delivery.

University of Nevada, Reno — Dr. Dean Burkin

Alpha-7 Integrin upregulation

Dr. Burkin, assistant professor of pharmacology, has developed an assay (scientific test) to identify compounds that can increase the production of alpha-7 integrin, a protein that stabilizes muscle membranes. With our support, Dr. Burkin is using his assay to search two libraries of FDA-approved drugs. We will use his assay to screen other drug libraries to expand the search for drugs that can counteract the muscle degeneration brought on by DMD.

University of Washington — Stanley Froehner, PhD

Phosphodiesterase Inhibitors

Dr. Froehner is testing phosphodiesterase inhibitors as potential drugs to treat DMD. PDE inhibitors may reduce inflammation, improve blood flow in the muscle, upregulate utrophin and inhibit myostatin, a negative regulator of muscle mass.

Parent Project Muscular Dystrophy — Cincinnati based foundation for Duchenne

Reauthorize the MD CARE act in order to maximize the collective DMD investment in research and move the field forward.