Today, SomaLogic and PPMD - together with several other Duchenne research groups - published a significant discovery that explains a technology allowing researchers to accurately measure the individual proteins in very small amounts of blood or other samples. By comparing patient and control samples, identification of critical differences in protein concentrations can be identified rapidly. These significantly different proteins can then be used as the basis for developing new diagnostic and therapeutic approaches, including their use as biomarkers for quickly assessing the efficacy of promising new drugs. This is incredibly promising news for our community.
Over the last 20+ years, I have seen /met more than 3,000 young men with Duchenne. Each young man is different, though it never really surprises me. My boys, Chris and Patrick were different in terms of strength. I often wondered why the difference, repeatedly asking myself questions about what might account for the variability. I worried a lot about it, asked clinicians, nutritionists, and physical therapists… everyone I met.
Genetic testing certainly shed some light on the issue; in that we know some mutations are ‘leaky’, some mild and others, more severe.
The use of steroids changed the natural history of Duchenne. In 1994, we were ‘importing’ deflazacort for families with friends in Italy and Switzerland. We believed that deflazacort seemed to have less impact on weight, more impact on height. Anecdotal evidence of course, but relevant nonetheless.
And over time, I noticed 4 distinct groups.
This variation was perplexing, we all wondered why. Normal was expected, anticipated, in the literature. Weight gain was often dismissed as due to dietary habits and while I agree, it can be managed with diet, some young boys gained no matter. The non-responders were puzzling as well and we wondered if their immune response was so significant that a higher dose might be required (recognizing it may be impossible due to toxicities) and the Becker-like response. Why? What else was going on?
I met Larry Gold over 10 years ago. Larry was on the board of PTC Therapeutics and focused on cancer, developing his aptamer technology around biomarkers. The premise of his work was a ‘footprint’ of proteins that were normal in health and altered in disease and that one might predict changes in health (or targets for treatment or impact of treatments) based on this ‘footprint’ of measuring a significant number of circulating proteins.
We discussed steroids and Duchenne, targets and Duchenne, everything and Duchenne. We agreed it was worth investigating the protein ‘footprint’. We wondered what we might find and if that might help explain the variability we see.
Cincinnati Children’s, Linda Cripe, MD led the project. Samples were sent, analyzed and following Larry called. It was incredible. The ‘arc’ in Duchenne was far, far different from their age-matched controls. 44 proteins were different, either up or down regulated. Some were ‘usual suspects’, inflammatory markers we expected. Others were surprising. But, it was a pilot. Larry said not to get excited. He collaborated with CINRG and validated the data. This is incredible news… another piece of the puzzle of Duchenne.
With luck, we will qualify this analysis, use the studies to determine impact of a certain therapy, demonstrated by a change in protein levels, and potentially identify new targets. This means that this data could be utilized as an outcome measure for clinical trials which could translate into fewer visits during a clinical trial as serum markers are tracked (blood drawn locally). It also translates into additional targets for therapy development. And perhaps best of all, having serum biomarkers would enable trials to include young men of all ages, ambulatory or not.
Elias Zerhouni (former director of NIH) said ‘mutations are the hardware of our lives; precision medicine will require understanding of the software’.
With collaborators like SomaLogic, we are getting there. For all of our sons.
Read PPMD's Press Release: