Thirty-two boys with Duchenne muscular dystrophy (DMD) hadstrengthened legs following treatment with myoblast transfertherapy (MTT), researchers report in the November/Decemberissue of Cell Transplantation.
The therapy involves injecting immature muscle cells(myoblasts) into several muscle groups to mitigate the muscleweakness caused by MD. Subjects in the study, aged 6 to 14years old, received 48 injections that delivered 5 billionmyoblasts into 22 major muscle groups in the lower body.
Peter Law, chairman of the Cell Therapy Research Foundation(CTRF) and principal investigator of the study, explained that"through cell fusion, the missing gene is incorporated into thedystrophic muscle cells to repair them." The study wasconducted at the CTRF in Memphis, Tenn.
To determine the efficacy of MTT, researchers used functionaltests using the KinCom Robotic Dynamometer, which measuredthe maximum isometric contractile forces of the ankle plantarflexors (AF), knee flexors (KF) and knee extensors (KE) beforeMTT and at three, six and nine months following MTT.
Law and his colleagues report that 88 percent of the AF, 49percent of the KF and 45 percent of the KE showed eitherincrease in strength or did not show continuous loss of strengthnine months after MTT.
Specifically, they found that at nine months after MTT, 60percent of the 60 AF examined showed a mean increase of 50percent in force, 28 percent showed no change and 12 percentshowed a mean decrease in force of 29 percent compared withthe function of the same muscles before MTT.
"The KF, being proximal muscles and more degenerative,showed no change in function at nine months after MTT," theinvestigators stated. Of the 60 KE examined, 23 percent showeda mean increase of 65 percent in force, 22 percent showed nochange and 55 percent showed a mean decrease of 24 percentin force at nine months.
The researchers also found that ambulatory subjects showedmore muscle improvement than the non-ambulatory subjectsat various times after MTT.
They concluded that more than 5 billion myoblasts arenecessary to strengthen both lower limbs of a DMD boybetween 6 and 14 years old and that "the more degeneratedproximal muscles will need more myoblasts per unit musclevolume than the distal muscles for MTT to be effective."
Subjects also received oral doses of the immunosuppressantcyclosporine beginning at two days before MTT and lasting forsix months after MTT to facilitate donor cell survival. Theresearchers found no evidence of an adverse reaction to eitherMTT or cyclosporine. The donor myoblasts were derived fromcell culture of muscle biopsies from males aged 9 to 21.
Law, the pioneer of MTT, began testing the therapy in February1990, when he injected 8 million myoblasts into one muscle inthe foot of a young patient with DMD. In previous papers, hereported that the MTT-treated foot showed levels ofdystrophin (the protein missing in people with DMD),improvement in cell structure and increased function. Sincethen Law has progressively increased the number of injectedmyoblasts and the number of body sites.
FDA has approved an ongoing protocol involving injection of 25billion myoblasts into 56 muscles located in the neck, arm,back, shoulder and abdomen. The study, approved fortreatment of 10 children, began in August. To date, eightchildren have received MTT, seven with DMD and one childwith infantile facioscapulohumeral dystrophy.
Founded in 1991, CTFR is also doing basic research oncardiomyopathy. Law said 10 percent of DMD children havethis disorder. He noted that two other research groups havedone research with MTT, one headed by Chuck Tremblay atLaval University in Quebec and another headed by Helen Blauat Stanford University. He said these teams have used MTT in asingle muscle.
-- Brenda Sandburg News Editor
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