DISEASE CLASSIFICATION(S):
Duchenne Muscular Dystrophy(DMD)
NAME OF CLINICAL TRIAL/STUDY:
Transplantation of self-derived muscle stem cells in DMD
TRIAL RESULTS:
2007
In a paper published in 2007 (see “Publications,” below), the investigators noted that there were no systemic adverse effects seen over a seven-month observation period following cell transplantation. They saw no local or systemic signs of inflammation; no structural abnormalities in the injected ADM muscle (the muscle that moves the little finger away from the hand) on MRI scans six months after transplantation; no alteration in function of the injected muscles; and no changes in cardiac function. Both stem-cell-treated and placebo-treated groups showed a moderate decrease of overall body strength, which the investigators say is likely related to the natural course of the disease.
PURPOSE AND RATIONALE:
Recent work supports the idea that stem cells reach the site of muscle regeneration and contribute to muscle repair as well as replenish the pool of repair cells following arterial injection, suggesting that this technique might be suitable for treating muscular dystrophy.
Although conclusive evidence is lacking, there are many reports suggesting that muscle-derived stem cells with a protein marker called CD133 may represent a population of muscle-generating cells located between muscle fibers.
This study aims to verify the safety of transplantation of muscle-derived CD133-positive, autologous (taken from the patients themselves) stem cells.
From a safety perspective, questions remain about whether adult stem cells in dystrophic muscle truly undergo functional integration and whether this may give rise to inflammation or formation of connective tissue.
STUDY DETAILS:
This is a double-blind, phase 1 clinical trial. This means neither investigators nor participants know who is receiving which treatment and that the trial is to assess the safety of the procedure. Participants will be randomly assigned to receive either stem cells or placebo (sham) cells.
Muscle cells will be taken from the tibialis anterior (muscle in the front part of the lower leg) and injected into the muscle that moves the little finger away from the hand.
Strength testing, blood tests, cardiac evaluations, pulmonary function tests, MRI scans, muscle biopsies and possibly other tests will be required.
CLOSING DATES:
2006
TARGET NUMBER OF PARTICIPANTS:
8
RECRUITMENT STATUS:
Closed
ELIGIBILITY REQUIREMENTS:
Participants must
- be at least 4 years old
- have a diagnosis of DMD confirmed by clinical evaluation, increase in levels of the muscle enzyme creatine kinase, muscle biopsy and dystrophin analysis
- be able to walk at the time of selection
- have adequate muscle strength and muscle bulk at the tibialis anterior (muscle at front of lower leg)
Participants must not
- be unable to walk
- have experienced symptoms before the age of 2-3
- have severe cardiac or respiratory dysfunction
- have a deficient immune system and/or autoimmune (self-immune) disease
- have any additional diseases, such as a family history of epilepsy or cerebral palsy
- be mentally retarded
- have any psychological or psychiatric disorders
- have been on steroid therapy in the previous six months
PUBLICATIONS:
Torrente Y, Belicchi M, Marchesi C, Dantona G, Cogiamanian F, Pisati F, Gavina M, Giordano R, Tonlorenzi R, Fagiolari G, Lamperti C, Porretti L, Lopa R, Sampaolesi M, Vicentini L, Grimoldi N, Tiberio F, Songa V, Baratta P, Prelle A, Forzenigo L, Guglieri M, Pansarasa O, Rinaldi C, Mouly V, Butler-Browne GS, Comi GP, Biondetti P, Moggio M, Gaini SM, Stocchetti N, Priori A, D'Angelo MG, Turconi A, Bottinelli R, Cossu G, Rebulla P, Bresolin N. Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients. Cell Transplantation 2007;16(6):563-77. PubMed summary
