Old and new therapeutic developments in steroid treatment in Duchenne muscular dystrophy

Abstract

Steroids have been used since two decades and several trials were conducted to establish their efficacy in DMD patients with various regimens. The clinical outcomes showed increased function in the treated boys, and in a single trial with deflazacort, prolongation of ambulation but with different side effects. Steroids clinical efficacy is now established. The main concern is to increase steroid efficacy and decrease side effect and toxicity. A trial comparing daily prednisone, deflazacort and intermittent glucocorticoids (prednisone 10 days on/10 days off) (FOR-DMD) is starting under NIH grant. The primary outcomes will be muscle strength, forced vital capacity and patient/parents satisfaction.

Figure 1.

Natural history of untreated DMD. Note a correlation between MRC score, strength of quadriceps muscle force by myometry and worsening of grading in 10 meters walking (1 to 7).

Figure 2.

(A) Medical Research Council (MRC) score in deflazacort and prednisone treated groups shows stabilization of strength after initial, slight improvement. Natural history controls show a continuous decline in strength. (B) Functional score in both the deflazacort- and prednisone-treated groups shows a slight improvement at the beginning of therapy, whereas the natural history group tends to increase in grade and worsen progressively. (C) Percentage of body weight increase in the deflazacort- and prednisone-treated groups. A less significant increase in weight was found in patients treated with deflazacort after 6 months. Filled square indicates prednisone group, open triangle indicates deflazacort group, and a cross indicates natural history group.

Figure 3.

Mechanism of steroid effect in DMD. The glucocorticoids increase total muscle mass and strength through Insulin like growth factors stimulation, decrease cytokine production and lymphocyte reaction, enhance myoblasts proliferation and synergistic molecules.

Figure 4.

Duchenne boys performing GSGC functional tests during a steroid trial: raising from the floor (G), climbing a stair (S), raising arms, raising from a chair (C).

Figure 5.

Steroid treated DMD patient walking at age 17 years.