research

Since Nov 2004, Charley’s Fund has committed $6.5 million to medical research. Our focus is translational research – research that has a real chance of reaching human clinical trial within five years. Our varied portfolio of investments includes world-renowned universities as well as start-up biotechnology companies. We fund scientists working all over the world, from Western Australia to South Plainfield, New Jersey.

funded research

AT 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.

AVI Biopharma – Portland, OR
Exon Skipping
Together with Ercole Biotech, this Portland, OR-based company holds the predominant patent estate for exon skipping technology. We have funded a one-year project to conduct research and preclinical testing. AVI is collaborating with Dr. Qi Lu of Carolinas Medical Center and Dr. Steve
Wilton of U of Western Australia in worldwide team effort to move this promising treatment forward.

BioFocus DPI – Netherlands
Utrophin Upregulation
Dr. David 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
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.

Carolinas Medical Center -- Qi Lu, PhD
Exon Skipping
Complementing Prosensa’s work, Principal Investigator Dr. Qi Lu and his team are fine-tuning systemic delivery of exon skipping. In a recently published paper, Dr. Lu showed for the first time that systemic delivery of exon skipping leads to functional improvement in a mouse model. Read Dr. Lu’s article in Nature Medicine. Thanks to Charley’s Fund, Prosensa and Dr. Qi Lu, two of the world leaders in exon skipping, are now collaborating for the first time. Read press release about collaboration.

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 degeneration 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
From previous studies, Dr. Martin concluded that Galgt2, a protein that adds sugars 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.

CombinatoRx -- Cambridge, MA
In November 2007, Charley's Fund teamed with the Nash Avery Foundation to invest $3 million in CombinatoRx, a unique pharmaceutical company focused on developing new medicines built from synergistic combinations of approved drugs. Our funding is being used for a 2-year research program with the specific aim of developing a treatment for DMD. CombinatoRx has assembled a highly qualified and motivated team for their DMD research. They are looking at millions of combinations of drugs that have been approved for other uses to see if any of the compunds can work in tandem to slow or stop the relentless progression of DMD. Dr. Benjamin Seckler and Dr. George Vella of Charley's Fund both serve on the Joint Research Committee that guides the scientific program. Click here to read a recent article about CombinatoRx in the New York Times.

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:

identifying key problems facing DMD researchers
seeking solutions via the world wide web for financial reward
applying solutions to expedite therapeutics development

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.

Prosensa - Leiden, The Netherlands
Exon Skipping
In November 2005, Charley’s Fund invested in Prosensa, a Dutch biotechnology firm that is developing a novel therapy for DMD called exon skipping. One month later, Prosensa was the first company in the world to earn orphan drug status from the FDA for this therapy. Prosensa has begun the first-ever human clinical trial of exon skipping. Read press release.

In this trial, researchers are injecting the biceps of boys with DMD to test safety and efficacy. The next step is to test intravenous systemic delivery so the therapy can be targeted to all the muscles of the body. For more information about this clinical trial, read an interview with Gerard Platenburg, Prosensa’s CEO

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 Leuven, Belgium -- Maurilio Sampaolesi, PhD
Stem Cells
The most promising long term therapeutic strategy for DMD is correcting the genetic defect at the DNA level. Dr. Sampaolesi is developing a program for the stem cell treatment of DMD patients. He is investigating methods to culture specific stem cells called "multipotent adult progenitor cells" for potential use as therapeutic gene therapy agents. Having a supply of stem cells will permit Dr. Sampaolesi to investigate the mode of delivery that will affect as many muscle cells as possible and assess the type, number and quality of clinical grade stem cells required to obtain FDA approval to proceed with a clinical trial on DMD patients.

University of Minesota - James Ervasti, PhD
TAT-Utrophin
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.

UNC Animal Models Core Facility -- Randy Thresher, PhD
New Mouse Model
We have awarded a grant to the UNC animal models core facility to develop a genetically modified mouse that mimics DMD in a human. Unlike the most widely used mouse in DMD research (mdx mouse), this new animal model contains human genetic material. This new model will be used to test the efficacy of systemic exon skipping, a required step before moving into human clinical trials.

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.

University of Western Australia – Dr. Steve Wilton
Exon Skipping
Research pioneer Steve Wilton, PhD is developing an exon-skipping “cocktail” which will measure skipping efficiency in DMD patient cells. This research complements the work being done by AVI Biopharma, the biotechnology firm in Portland, OR that we are funding. Dr. Wilton’s work will help make exon skipping applicable to more children with DMD.

On Our Radar

Santhera
a Swiss biotechnology company developing a drug (calpain blocker) that aims to slow the progression of DMD.

Asklepios
a biopharmaceutical company that recently launched the first human gene therapy trial targeting DMD Read article.

Johns Hopkins University – Hal Dietz, MD.
Dr. Dietz recently found that a commonly prescribed blood pressure medication, Losartan, improved muscle regeneration and repair in the mdx mouse model.
Researchers are in the process of organizing a clinical trial for DMD cohorts.

HCT – 1026
A group in Italy recently described the use of a nitric oxide (NO)-releasing compound that also functions as an anti-inflammatory. The drug, called HCT-1026, behaves as an NO donor (stimulating the up regulation of NOS). HCT1026 was tested in mice with muscular dystrophy for one year and was shown to slow the progression of the dystrophic condition. Human clinical trials are being considered.

Stem Cell Therapy -- Dr. Giulio Cossu
Giulio Cossu and co-workers in Milan reported in the November 30th 2006 issue of Nature that dogs with muscular dystrophy who received a type of stem cell called mesangioblasts from a single donor had significant improvement over untreated control animals. Human clinical trials are being considered in the next two to three years.

Myo-029 -- Wyeth Pharmaceutical
An antibody that inhibits myostatin activity (Myo-029) has been tested in Phase I/II clinical trials. Results from the trial will be released in the spring of 2007

Trichostatin A -- Dr. Lorenzo Puri – Burnham Institute
Trichostatin A (TSA), used to treat breast cancer patients, was found to regenerate wasted muscles in a mouse with muscular dystrophy. Plans for human trials are currently being defined.