Mecasermin is a bioengineered protein that mimics the behavior of naturally occurring insulin-like growth factor 1 (IGF-1). Discovered in the late 1980s, this growth factor carries significant relevance in human health and disease management.
Background of Mecasermin
Mecasermin, also known as recombinant human insulin-like growth factor 1 (rhIGF-1), was discovered as a part of research aimed at replicating the protein structure of IGF-1. IGF-1 is expressed from the IGF1 gene, which is located on the long arm of chromosome 12 at locus 12q23.2.
The protein structure of Mecasermin represents a single chain polypeptide that comprises 70 amino acids. It is structurally similar to proinsulin, which is divided into four domains, B, C, A, and D. In particular, domains B and A exhibit high similarity to insulin and are believed to engage in receptor activation.
Mecasermin Function and Signaling Pathways
Mecasermin essentially functions as an endocrine hormone and a growth factor. It recognizes and binds to the IGF-1 receptor, stimulating several intracellular signaling pathways. The two most notable are the phosphatidylinositol 3-kinase (PI3K)/Akt and the Ras/Raf/MAPK pathways.
The PI3K/Akt pathway regulates cellular processes related to growth, proliferation, survival, and metabolism. This particular pathway prevents apoptosis, facilitating cellular survival. The Ras/Raf/MAPK pathway is integral for cellular proliferation and differentiation.
Mecasermin-Related Diseases
IGF-1 deficiency, including growth hormone insensitivity syndromes (GHIS) and Laron syndrome, is directly associated with Mecasermin. This deficiency results in growth failure, short stature, and prolonged lifespan.
The introduction of Mecasermin has transformed the management of these health conditions. It plays a critical role in the development of long bones and body growth, and it is pivotal in metabolism regulation, demonstrating an insulin-like effect that aids glucose uptake in the muscles.
The Application of Mecasermin in Medicine
Mecasermin has been approved by the FDA for long-term management of growth failure in pediatric patients with severe primary IGF-1 deficiency or those with GHIS, as these patients present low levels or even absence of endogenous IGF-1.
Multiple studies have confirmed that prolonged use of Mecasermin in affected patients can significantly improve their linear growth velocity and height standard deviation scores. Alongside growth improvement, Mecasermin also helped to fibrate metabolism, contributing to lower levels of total cholesterol and low-density lipoprotein cholesterol.
List of Drug Candidates Related to Mecasermin
Mecasermin (marketed as Increlex) is currently the only approved rhIGF-1 therapy for long-term treatment in growth failure due to primary IGF-1 deficiency. However, there are several other drug candidates with similar growth promoting properties including Mecasermin Rinfabate (also known as Iplex), a complex of rhIGF-1 and rhIGFBP-3 (recombinant human IGF-binding protein 3). This drug previously had FDA approval but was withdrawn due to manufacturing difficulties.
In summary, Mecasermin, a recombinant reproduction of endogenous IGF-1, carries immense implications for metabolic processes and systemic growth regulation. Its therapeutic potential serves as a ray of hope for patients suffering from malfunctioning growth regulation. It's a testament to the evolution of genetic engineering, offering solutions to severe health conditions and improving the quality of life for many.
