A biomarker is any biological indicator that doctors or researchers can objectively measure and evaluate to determine the state of an individual’s health, confirm disease onset and progression, or gauge whether an experimental treatment is working or not.
Some common, everyday types of biomarkers include body temperature, blood pressure, pulse, heart rate, and the presence or absence of particular proteins in the blood or urine. But in neuromuscular disease management and research, more specialized biomarkers are needed.
Diagnostic biomarkers help physicians identify, confirm or rule out a diagnosis, while prognostic biomarkers help determine the likely progression of disease without treatment.
Predictive biomarkers tell physicians or researchers whether, or how well, an individual is likely to respond to a proposed therapy.
Pharmacodynamic biomarkers indicate how a drug behaves in the body (including whether, and how much of, a drug reaches its target; correlations between dose and response; and the presence or absence of various other intended or unintended effects).
Biomarkers in trials
In what may be their most important role, biomarkers help drug development teams to assess in human clinical trials whether an experimental therapeutic reaches selected targets within the body and produces the desired responses.
Both prognostic and predictive biomarkers can serve as powerful patient selection tools by helping define the inclusion and exclusion criteria that determine clinical trial eligibility.
Biomarkers also can help researchers ensure that randomized study groups within a trial are similar. Pharmacodynamic biomarkers give critical information about the experimental treatment’s activity and effects in the body.
Ideally, biomarkers must demonstrate solid accuracy and consistency in measurement, both within a single individual and across a group of individuals.
Good biomarkers should demonstrate a clear link either to a specific disease, a specific experimental therapy or both.
A relatively easy method should exist for clinicians or researchers to take the samples they need for measurements. The more invasive and inconvenient the sampling procedure, the less willing patients may be to submit to it.
Other considerations include expense, data turnaround time and standardization across a disease.
Most of the biomarkers currently in use in neuromuscular disease research don’t yet meet all these criteria, but nonetheless provide scientists and physicians with useful information.
MDA-funded researchers already use biomarkers in neuromuscular disease research, and are continually working on development of additional biomarkers.
If the gene mutation underlying a disease is known, that mutation is a reliable diagnostic biomarker — if a person has the mutation, he or she probably has or will get the disease. But what researchers really want are more prognostic and pharmacodynamic biomarkers — those that can reliably predict the course of the disease or indicate the biological activity of an experimental treatment.
For example, a commonly used biomarker for muscle degeneration is the blood level of the enzyme creatine kinase, which leaks out of severely damaged muscles. The amount of dystrophin (the protein that is missing or deficient in muscles in Duchenne and Becker muscular dystrophy) is a commonly used biomarker in these diseases.
Also, imaging techniques such as MRI currently are being evaluated for their ability to identify biomarkers in DMD, limb-girdle muscular dystrophy and other diseases, by revealing signs of muscle damage and degeneration.
Biomarkers in spinal muscular atrophy include the amount of SMN1 and SMN2 proteins, and the number of copies of the SMN2 gene.
In acid maltase deficiency (Pompe disease), urine concentrations of the carbohydrate Hex4 provide an indication of muscle damage, as well as information about the patient’s ability to regulate stored sugar in muscles. Hex4 concentrations also can provide an indirect indication of the response of an individual with Pompe disease to treatment with enzyme replacement therapy.
The future of biomarkers
Biomarkers will play a critical role in personalized medicine, in which treatments are based on an individual’s specific genetic makeup.
Increased identification and use of biomarkers will help speed the pace of research and, ultimately, the development of safe and effective therapies.