Chapter 16 — Further Reading

IGF-1, Myostatin Inhibitors, and the Muscle-Building Peptides

Sources are described by what they are and what they will teach you, rather than listed as citations. Search terms are given where they will help. Appendix M explains how to find and read a primary source without a university library subscription.

Tier 1 — Start here

The original myostatin identification papers (mid-to-late 1990s). Search: myostatin GDF-8 negative regulator skeletal muscle mass. The founding work identified the gene and characterized the null-mouse phenotype, and the follow-up work connected it to double muscling in cattle. Read these for the pleasure of watching a mechanism get established cleanly — and note how quickly the cattle connection was made once the gene was in hand.

The 2004 human case report of myostatin loss of function. Search: myostatin mutation muscle hypertrophy child case report 2004. A short paper, readable in twenty minutes. Read it for what a well-written n = 1 looks like: what the authors claim, how carefully they hedge, and what they explicitly decline to conclude.

Contemporary consensus definitions of sarcopenia. Search: sarcopenia consensus definition revised criteria muscle strength. Read the section that explains why strength replaced mass as the leading criterion. This is the clearest available example of a research field revising its own definition on evidence, and it is the single most useful outside reading for §16.6.

Any accessible review of surrogate versus clinical endpoints in drug regulation. Search: surrogate endpoint validation clinical outcome regulatory. You do not need a muscle-specific one; the logic is general and transfers to every chapter of this book.

Tier 2 — Go deeper

Reviews of myostatin-pathway inhibitors in neuromuscular disease. Search: myostatin inhibitor clinical trials muscular dystrophy review outcomes. Look for reviews written after roughly 2020, when enough programs had reported for the pattern to be visible. Read them specifically for the endpoint tables: which trials measured function, which measured only body composition, and what happened in each.

The IGF binding protein literature. Search: IGFBP-3 acid-labile subunit ternary complex bioavailable IGF-1. This is where the §16.2 molecule box comes from, and it is more interesting than it sounds — a regulatory system built entirely out of controlled sequestration.

Mecasermin's prescribing information. Search the FDA label directly. Read the indication statement and the warnings section. This is a useful exercise in how narrowly a real approval is written, and how much of a label is about the risks rather than the benefits.

The whippet myostatin paper. Search: myostatin mutation whippet racing performance. Read it for the heterozygote finding, which is the most interesting single data point in the animal literature and is almost never mentioned by people citing the animal literature.

Prospective cohort meta-analyses of circulating IGF-1 and cancer incidence. Search: circulating IGF-1 cancer risk meta-analysis prospective cohort. Then search additionally for Mendelian randomization IGF-1 cancer. Read the two literatures side by side and notice how carefully the better papers phrase their conclusions.

Resistance training in older adults. Search: progressive resistance training older adults strength physical function systematic review. This is the ✅-grade intervention of §16.7 and it deserves more of your reading time than any compound in this chapter.

Tier 3 — For the committed

The specific-force literature in myostatin-null animals. Search: myostatin null mice specific force muscle quality. Technical muscle physiology. Worth the effort because it is the mechanistic bridge between the animal photographs and the human trial results, and because reading it is a lesson in how a finding can be present in the literature and invisible to the field at the same time.

Follistatin structure, isoforms, and binding promiscuity. Search: follistatin isoform FS-288 FS-315 activin myostatin binding. Read enough to understand why "follistatin-344" is a confusing product name and why glycosylation makes the identity question unanswerable from outside.

Follistatin gene therapy early-phase trials. Search: AAV follistatin gene therapy muscular dystrophy inclusion body myositis. Small, open-label, and frequently miscited. Read the methods sections carefully so you can articulate exactly how far these are from an injectable product.

The IGF-1R inhibitor oncology programs. Search: IGF-1R inhibitor clinical trials oncology failure. A whole drug class built on excellent mechanism that largely disappointed in the clinic. It is the same lesson as this chapter's, arriving from the opposite direction: blocking a growth pathway did not reliably shrink tumors any more than blocking a brake reliably improved function.

The GH receptor deficiency cohort literature. Search: growth hormone receptor deficiency cohort cancer diabetes incidence. Small, genetically distinctive, decades of follow-up. Read it for what a low-powered observation with a large apparent effect can and cannot support.

World Anti-Doping Code prohibited list, current edition. Freely available. Find the entries covering growth factors and agents modifying myostatin function. Useful for anyone in tested sport and useful generally as a picture of what regulators think is worth prohibiting versus what has been shown to work — two different lists.

If you only do one thing

Read the sarcopenia consensus definition, and specifically the passage explaining why low muscle strength replaced low muscle mass as the leading diagnostic criterion.

It takes fifteen minutes. It is not about peptides at all. And it is the strongest possible independent confirmation of §16.6, because it comes from a field with no stake in this argument: a body of researchers looked at their own data, concluded that the measurement in their discipline's name was not the one that predicted outcomes, and changed the definition.

If a field can do that about itself, a reader can do it about a compound they were hoping would work.