These phase 1 studies examine a possible new treatment for myotonic dystrophy type1 (DM1), the most common form of adult muscular dystrophy. At present no treatment exists to reverse its progressive wasting and weakness. Low levels of testosterone and growth hormone, as well as insulin resistance, appear to contribute to the muscle loss, but therapeutic trials to reverse these hormonal abnormalities have failed to produce significant improvement. A previous trial of insulin-like growth factor-1 [IGF1] has offered promise. Treatment with rhlGF1 increased strength, protein synthesis, and insulin action in 7 patients but side effects caused 2 to drop out. A new, better tolerated, longer acting, preparation of rhlGF1, is now available from INSMED. It is SomatoKine, rhlGF1 in complex with recombinant human IGF binding protein 3, and it will be used in this proposal. Preliminary studies show it is safe and well tolerated in healthy adults, diabetics, and older women treated after hip fracture. We will evaluate SomatoKine in DM1.
The aim of this proposal is to evaluate the safety and feasibility of daily subcutaneous injections of SomatoKine for treatment of muscle wasting and weakness by performing two sequential studies, each involving 15 patients with DM1: 1st) An initial 24-Week Dose Escalation Study of SomatoKine [0.5, 1.0, and 2.0 mg/kg, with each dose given daily for 8 weeks] to identify an """"""""optimal dose"""""""" based upon the side effects, drug levels, and efficacy [dual energy x-ray absorptiometry (DEXA); quantitative myometry; manual muscle strength testing] observed at each dose; 2nd) A subsequent 24-Week study of SomatoKine using an """"""""Optimal Dose"""""""" to demonstrate its safety and feasibility as a daily treatment for a six month period. In addition, we will search for evidence of altered signaling along the intracellular pathway for IGF1 by measuring phosphorylation of p70S6K in needle muscle biopsy specimens obtained from 10 DM1 patients in the 24-Week """"""""Optimal Dose"""""""" SomatoKine Study and from 10 age-gender matched normal volunteers who will receive SomatoKine for only two days. Specimens will be obtained from vastus lateralis muscle before and after two days of """"""""optimal dose"""""""" treatment. These studies will test our hypothesis that supraphysiologic levels of IGF1 are safe and well tolerated and provide preliminary data regarding efficacy (reversal of muscle wasting and weakness.) If the results of this project prove promising, we plan to carry out a larger, multi-center, phase 2, controlled trial of SomatoKine.
Showing the most recent 10 out of 88 publications
