Method of in vitro preconditioning healthy donor's myoblasts before transplantation thereof in compatible patients suffering of recessive myopathies like muscular dystrophy, for improving transplantation success

US5833978A · kind A · utility

Assignee

• Université Laval · CA

Inventor

• Jacques P. Tremblay · Laurelbrook Court, CA

Key dates

• Filing date: Mar 16, 1995
• Grant date: Nov 10, 1998
• Expiry date: Mar 16, 2015

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K48/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A method of pretreating healthy donor's myoblast cultures with growth or trophic factors like basic fibroblast growth factor (bFGF) on transplantation to subjects suffering of recessive myopathy like muscular dystrophy is disclosed and claimed. Recipient muscles show a higher percentage of functional cells, demonstrated by the higher incidence of dystrophin-positive fibers, and does not require previous preconditioning of recipient muscles by irradiation or toxin administration. Donor mouse myoblasts expressing the reporter gene .beta.- galactosidase were grown with 100 ng/ml bFGF during the last two days before injecting them in the left tibialis anterior (TA) muscles of recipient MHC-compatible mdx mice, an experimental animal model of muscular dystrophy. Myoblasts from the same primary cultures were also grown without bFGF and injected in the right TA muscles as control. The recipient mice were immunosuppressed with FK 506. Twenty-eight days after myoblast transplantation, the percentage of .beta.- galactosidase-positive fibers was significantly higher (more than a 4 fold increase) following culture with bFGF than without bFGF. Almost all .beta.-galactosidase-positive-fibers wer…