IGF-1 Continues to Show Promise

GOOD NEWS on the Research Front

 

MDA’s Quest Magazine just published an update on IGF-1. Maria Pennuto, a previous recipient of a KDA Research Grant and MDA funding, provided the following update to reporter Amy Madsen.

I have written about IGF-1 in several previous posts because of its potential. We hope to hear more promising news at the upcoming KDA Conference and Educational Symposium the second week of October in New Orleans.

______________________ 

SUMMARY

• Mice with a disease resembling spinal-bulbar muscular atrophy (SBMA) that were treated with an insulin-like growth factor 1-based compound had better motor function, slower weight loss, improved muscle health and increased survival time.
• Recent studies have shown that IGF1 works in SBMA by reducing toxicity caused by a mutation in the androgen receptor (AR) gene; it also helps promote muscle and nerve growth.
• The new findings suggest that IGF1 potentially may be effective in ameliorating the disease.

Mice with a disease resembling spinal-bulbar muscular atrophy (SBMA, or Kennedy’s disease) that were treated with a compound based on insulin-like growth factor 1 (IGF1) had better motor function, slower weight loss, healthier muscles and longer survival time than mice that received an inactive substance, an MDA-supported research team has reported.

The research team also found that SBMA mice that overproduce a muscle-specific form of IGF1 have a milder disease course than mice that produce less of the protein.

The new findings suggest that IGF1 potentially may be effective in ameliorating the disease via at least two mechanisms:

• directly reducing toxicity caused by a mutation in the androgen receptor (AR) gene by changing the way the androgen receptor protein behaves; and
• generally promoting and regulating skeletal muscle growth, and improving survival of muscle-controlling nerve cells called motor neurons.

The research team reported its findings online Aug. 29, 2012, in Molecular Medicine. To read the full report, see IGF-1 Administration Ameliorates Disease Manifestations in a Mouse Model of Spinal and Bulbar Muscular Atrophy. MDA supported Maria Pennuto at the Italian Institute of Technology in Genoa, Italy.

Findings show IGF1 compounds hold therapeutic potential
 
The researchers treated SBMA mice with a compound called mecasermin rinfabate (brand name Iplex), which is a combination of IGF1 and IGF1 binding protein 3. (The binding protein helps IGF1 last longer in the body.)

Male mice were randomly assigned to receive abdominal injections of the IGF1-based compound at a daily dose of 15 milligrams per kilogram of body weight, or an inactive substance. To mimic the typical clinical setting (in which a diagnosis of SBMA occurs after symptoms appear) the researchers began injections when the mice were 10 weeks old, after disease onset, and continued through 20 weeks.

The researchers evaluated body weight, motor function and survival in the mice. They found that, when compared to the placebo-treated mice, those treated with IGF1 had:

• less body weight loss;
• significantly improved grip strength; and
• longer survival time (by an average of approximately three weeks).

In addition, the researchers found that the IGF1-treated mice had markedly reduced muscle shrinkage (atrophy) and degeneration.

The study results provide a basis for further study of IGF1-based compounds as potential therapies for people with SBMA.