Updated 5/5/02- Matt's Results
Gentamycin is antibiotic that may be able to help boys with DMD due to a Stop Codon causing the problem with Dystrophin producton. Now this problem only occurs in only 10-15% of the boys with DMD. The rest of the boys have different types of problems with their dystrophin (deletion of the gene). The follwing link explains this in alot better detail and provides additional links to gentamycin articles. Gentamycin will help the gene ignore the Stop Codon and produce some dystrophin. We need about 20% of normal dystrophin to hopefully stop the further deterioation of muscles. Gentamycin will not be a cure, in that it will not repair muscles already damaged where fibrosis has set in.
Matt was accepted into the Ohio State (OSU) Phase I Gentamicin Study in March 2000 after DNA testing indicated that he did indeed have a Stop Codon. Matt has a causative mutation found in dystrophin gene representing a nonsense mutation in Exon 7, C189, with an Amino Acid Change of gln>ter. The study took place over 15 days at the OSU Medical Center. After the initial testing, two follow-up exams were held at two week intervals. We selected April 3 as the starting date for Matt's study.
On April 3, 2000, we checked Matt into the OSU Hospital in the General Clinical Research Center (GCRC). The first day wass for getting baseline information on the patient. Since we were able to get a portion of Matt's orginal muscle biopsy from 1996 at Dr. Hoffman's lab, a new biopsy sample was not necessary. Matt had blood drawn to evaluate his creatine clearance levels. He also had a 24 hour urine sample for kidney function. He was also evaluated in the MDA Clinic's muscle lab for a baseline on his strength. Finally, a baseline of hearing function is taken. Potential side effects from gentamicin are kidney and hearing problems. These last two tests take about a hour each. That completed the first day.
On day two, gentamicin infusion began and continued for 14 days. The dosage is calculated based on weight and kidney functions. Treatment was administered once a day through a catheter and took about one hour. Vital signs (blood pressure, breathing rate, pulse, and temperature) were checked 3 times a days. Also, blood was tested for drug levels every three days. A 24 hr urine sample was collected again on days 7 and 14 for kidney function. On day 15, he repeated the muscle and hearing tests. Also, a new muscle biopsy was taken. The new biopsy was analyzed for the presence and amount of dystrophin to determine if gentamicin worked or not.
Overall, the study went very well for Matt. He appeared to have no adverse reactions as his blood, urine and hearing remained the same. He went back twice in May for the follow-up exams where his breathing and muscle function were measured again. In addition, a blood sample was taken on each of the follow-up visits.
We finally got the results back from the testing. The results were not what we had hoped for. Matt's biopsy had no dystrophin present in the muscle tissue! However, during the time Matt was taking Gentamicin, his CPK levels dropped. They were still elevated well above normal levels, but significantly less than level at start of the study. After the study, the CPK levels shot back up to the prestudy levels.
The question remains if this is bad or slightly good news. Some have indicated that maybe the study period was too short for gentamicin to start the production of dystrophin. Another issue is whether the reduction of CPK while taking the drug means there is less muscle tissue damage occuring. I am disappointed in the results. The lack of dystrophin to me means it did not work. Matt was given a high dose for 15 days and it did not work as planned (dystrophin should have been produced). I am undecided myself as to whether the lowering of CPK during treatment is actually good or not.
Overall, this has been very discouraging news for us. We had high hopes when Matt was admitted to the program. As with every other "new discovery" during the last 5 years in the DMD field, it seems another idea has been shot down or delayed while the kinks are worked out. I wish we had more encouraging results to report, but it was not meant to be.
***These are my opinions and the results only for Matt. It does not attempt to report the results of the entire study. Dr. Mendell did not want the results released until they have had time to work out all the details. I waited for a long period for posting the results. However, I get a lot of questions about the results. Therefore, I felt this was the right time to get Matt's results and my intrepretation of those results out for people to see.
The nurses and Dr. Jerry Mendell were all great to Matt. They made the time go by very fast. We want say thank you to all the nurses of the GCRC.
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