IGF-1 for MD

[Andy]

Hi guys ,

Been reading a bit on the human growth hormone IGF-1 ,

there was one drug already proved safe in other trials entering a phase II study for ALS ,

is there any reason why people with MD shouldn't try IGF-1 type drugs under medical supervision ?

[David Feder]

It's possible that IGF-1 can help.

Rskalpha-actin/hIGF-1 transgenic mice with increased IGF-I in skeletal muscle and blood: impact on regeneration, denervation and muscular dystrophy

1: Growth Horm IGF Res. 2006 Jun;16(3):157-73. Epub 2006 May 22
Shavlakadze T, Boswell JM, Burt DW, Asante EA, Tomas FM, Davies MJ, White JD, Grounds MD, Goddard C.
School of Anatomy and Human Biology, The University of Western Australia, Crawley, Perth. [e-mail]

Human IGF-I was over-expressed in skeletal muscles of C57/BL6xCBA mice under the control of the rat skeletal alpha-actin gene promoter. RT-PCR verified expression of the transgene in skeletal muscle but not in the liver of 1- and 21-day old heterozygote transgenic mice. The concentration of endogenous mouse IGF-I, measured by an immunoassay which does not detect human IGF-I, was not significantly different between transgenic mice and wild-type littermates (9.5 +/- 0.8 and 13.3 +/- 1.9 ng/g in muscle; 158.3 +/- 18.6 and 132.9 +/- 33.1 ng/ml in plasma, respectively). In contrast, quantitation with antibodies to human IGF-I showed an increase in IGF-I of about 100 ng/ml in plasma and 150 ng/g in muscle of transgenic mice at 6 months of age. Transgenic males, compared to their age matched wild-type littermates, had a significantly higher body weight (38.6 +/- 0.53 g vs. 35.8 +/- 0.64 g at 6 months of age; P < 0.001), dry fat-free carcass mass (5.51 +/- 0.085 vs. 5.08 +/- 0.092 g; P < 0.001) and myofibrillar protein mass (1.62 +/- 0.045 vs. 1.49 +/- 0.048 g; P < 0.05), although the fractional content of fat in the carcass was lower (167 +/- 7.0 vs. 197 +/- 7.7 g/kg wet weight) in transgenic animals. There was no evidence of muscle hypertrophy and no change in the proportion of slow type I myofibres in the limb muscles of Rskalpha-actin/hIGF-I transgenic mice at 3 or 6 months of age. Phenotypic changes in Rskalpha-actin/hIGF-I mice are likely to be due to systemic as well as autocrine/paracrine effects of overproduction of IGF-I due to expression of the human IGF-I transgene. The effect of muscle specific over-expression of Rskalpha-actin/hIGF-I transgene was tested on: (i) muscle regeneration in auto-transplanted whole muscle grafts; (ii) myofibre atrophy following sciatic nerve transection; and (iii) sarolemmal damage and myofibre necrosis in dystrophic mdx muscle. No beneficial effect of muscle specific over-expression

www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16716629&query_hl=2&itool=pubmed_docsum


Comparative evaluation of IGF-I gene transfer and IGF-I protein administration for enhancing skeletal muscle regeneration after injury
1: Gene Ther. 2006 Dec;13(23):1657-64. Epub 2006 Jul 27
Schertzer JD, Lynch GS.
Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Grattan Street, Victoria 3010, Australia.

Developing methodologies to enhance skeletal muscle regeneration and hasten the restoration of muscle function has important implications for minimizing disability after injury and for treating muscle diseases such as Duchenne muscular dystrophy. Although delivery of various growth factors, such as insulin-like growth factor-I (IGF-I), have proved successful in promoting skeletal muscle regeneration after injury, no study has compared the efficacy of different delivery methods directly. We compared the efficacy of systemic delivery of recombinant IGF-I protein via mini-osmotic pump (approximately 1.5 mg/kg/day) with a single electrotransfer-assisted plasmid-based gene transfer, to hasten functional repair of mouse tibialis anterior muscles after myotoxic injury. The relative efficacy of each method was assessed at 7, 21 and 28 days post-injury. Our findings indicate that IGF-I hastened functional recovery, regardless of the route of IGF-I administration. However, gene transfer of IGF-I was superior to systemic protein administration because in the regenerating muscle, this delivery method increased IGF-I levels, activated intracellular signals (Akt phosphorylation), induced a greater magnitude of myofiber hypertrophy and hastened functional recovery at an earlier time point (14 days) after injury than did protein administration (21 days). Thus, the relative efficacy of different modes of delivery is an important consideration when assessing the therapeutic potential of various proteins for treating muscle injuries and skeletal muscle diseases.

davidfeder.proboards75.com/index.cgi?board=general&action=post&thread=1179231240&page=1


Insmed Announces Promising Results From IPLEX Phase II Myotonic Muscular Dystrophy Clinical Study
www.cnw.ca/fr/releases/archive/May2007/03/c4506.html