Funded By:
For further information on this study contact Ted Abresch at UC Davis, (tabresch@ucdavis.edu) at the University of California, Davis, Center for the Study of Neuruomuscular Diseases (RRTCNMD) .
Further information is available at http://clinicaltrials.gov/. The web site of CINRG ( http://www.cinrgresearch.org/UCD0305.shtml) also has information on this study.
The other partners in the Cooperative International Neuromuscular Research Group (CINRG) will be accepting patients into this study. Keep your eye on the UC Davis RRTC web site or the CINRG web site for announcement of their participation in this study. There are currently 19 sites participating in this study. A listing of the actively recruiting sites is available on the http://clinicaltrials.gov/ web site.
There are several new clinical trials getting underway to study genetic defects that are found in Duchenne muscular dystrophy (DMD). Two will study drugs that will prevent the action of a “stop codon” and the other will examine a drug that promotes exon skipping. With both of these abnormalities the muscles lack functional dystrophin molecules.
Stop Codon : One of the genetic abnormalities found in boys with Duchenne muscular dystrophy (DMD) is the presence of a “stop codon.” This abnormality results in the cells being told to stop the production of the protein dystrophin before the entire functional protein has been formed. PTC124, a drug produced by PTC Therapeutics of Plainfield , NJ , causes the cells to ignore the stop message in the DNA. This may allow the production of functional dystrophin by the cells and has been shown to be effective in animal studies.
1- In October of 2006 promising results were released based on testing two doses of PTC124 in 26 boys with Duchenne muscular dystrophy (DMD). In three of six boys who took the low dose and in eight of twenty who had the high dose, the presence of dystrophin was observed in muscle biopsies. In the high dose group there was also a reduction in the serum creatine kinase level. Based on these positive results, a phase two clinical study to evaluate higher doses of the experimental compound PTC124 is beginning. For more detailed information about this study, go to the clinicaltrials.gov web site. or contact Diane Goetz at PTC Therapeutics, (908) 912-9256 dgoetz@ptcbio.com . The results of a Phase 1 clinical trial of PTC 124 in healthy adults are published in the Journal of Pharmacology, 2007;47:430-444.
2- Another trial will study the use of Gentamycin to allow the “read through” of a stop codon and will begin soon at the Columbus Children's Research Institute. This phase 1 trial will test the safety of administering intravenous doses of Gentamycin to boys with DMD. Preliminary information on this trial may be found at clinical trials.gov.
Exon skipping: Exon skipping is somewhat different than ignoring the stop codon. It will cause the skipping of a genetic error anyplace in the large dystrophin gene. This is accomplished using antisense oligonucleotides (AON) (short pieces of DNA or RNA) that will mask the faulty area of the DNA and allow the dystrophin protein to be formed almost normally. This type of therapy has been tested successfully in mice.
1- A group at Leiden University in the Netherlands is beginning a trial of 4 – 6 boys to study the safety, the efficacy and the tolerability of a single muscular injection of an AON. The compound being tested was developed by a Dutch biopharmaceutical company, Prosensa ( www.prosensa.nl ). The trial, already fully enrolled, will give an indication of whether this is an approach that should be further pursued.
2- Another study to assess the possibility of using antisense oligonucleotides in the treatment of DMD is about to begin in England . This study will use a different drug (AVI-4658 PMO). Further information on this trial can be found at the clinicaltrials.gov web site.
Other CINRG studies of DMD can be found on the CINRG web site: http://www.cinrgresearch.org/Genetic_research_muscular_dystrophy.shtml
This site lists clinical trials that are currently recruiting subjects, those that have completed recruitment and upcoming clinical trials.
For an excellent discussion of clinical trials, what they are, who can participate, how to participate and a wealth of other general information go to the Resource page of ClinicalTrials.gov: Click here for the link.
ClinicalTrials.gov provides regularly updated information about federally and privately supported clinical research in human volunteers. ClinicalTrials.gov gives you information about a trial's purpose, who may participate, locations, and phone numbers for more details. The information provided on ClinicalTrials.gov should be used in conjunction with advice from health care professionals.
The Partnership for Human Research Protection, Inc. (PHRP) is launching a national campaign to educate people considering participating in clinical research trials about the risks and benefits of clinical research. PHRP is a collaboration between the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and the National Committee for Quality Assurance. Available on their web site is a list of questions for those considering participation in clinical trials to ask. For list of questions click here.
The U.S. Department of health & Human Services, Office for Human Research Protections (OHRP) has also published a brochure for those interested in becoming a research volunteer. The brochure is availble for down load at the OHRP web site. There is also a toll free telephone number to order free copies of the brochure. Click here to accesss the site. There are also links to other web sites that list clinical trials and to a list of questions you can use in evaluation of your participation in a clinical research study.
To view PDF files associated with the clinical studies information, you will need Adobe Acrobat Reader.
Other clinical studies for the 2003-2008 funding cycle of the RRTC/NMD are in the formative stages. For information on upcoming studies see the Overview of the RRTC/NMD 2003-2008. Check this site for announcement of opportunities to participate in the studies.
