Precision Medicine and Rube Goldberg

Precision Medicine and Rube Goldberg

The American cartoonist and inventor Rube Goldberg was best known for his series of cartoons featuring absurdly intricate contraptions designed to perform mundane tasks. The humor comes from the apparent simplicity of the task: Why not just take the egg into one’s own hands and crack it open? However, Rube Goldberg was onto something: We humans are living Rube Goldberg machines. That simple act of cracking open an egg requires an inordinately complex sequence of events to occur within our bodies.

We know that such a simple act requires exquisite coordination between body and brain. However, this interaction is just the surface. If we probe deeper (to the molecular level), we can see an orchestra of DNA, RNA, and proteins working in harmony to carry out the egg-breaking. When everything works in a harmonious balance, we are fine. When discord arises, disease often results. By probing the different players of the molecular biology trilogy, unique understandings about the disease can be gleaned and harnessed for the implementation of precision medicine.

Yet, we must be cautious about which molecules we monitor for precision medicine because the realization of our own inherent complexity holds especially true in the doctor’s office. Take cancer treatment as an example. Not only are cancer genomes highly variable (Tomasetti, Vogelstein, & Parmigiani, 2013; Vogelstein et al., 2013), but cancers can be affected by numerous molecular pathways (Loeb & Loeb, 2000). As a result, successful treatments for one type of cancer do not always work efficiently for other cancers — or even other tumors of the same type of cancer!! — even though they share the same mutations (Kobayashi & Mitsudomi, 2016; Kopetz et al., 2010; Prahallad et al., 2012).

To develop medicines with greater precision, we certainly should tap into the data geyser born from the omics revolution. Before tapping in, however, we need to determine just what information we really need and how to put it together. This knowledge makes the path clearer for harnessing the wealth of data to make the vision of precision medicine a reality.

Historically, research fixated on specific pathways or individual proteins, but this approach has nearly maxed out the potential benefits regarding our understanding or providing new treatments for cancer (Sapiezynski, Taratula, Rodriguez-Rodriguez, & Minko, 2016). For the next generation of medicines/treatments, we will need to look at how numerous pathways influence one another and how they may differ among individuals. Already, this realization has birthed yet another omics, known as interactomics.

What in the world is interactomics? In essence, it’s about looking at how all the proteins interact with one another and how the interactions change in real-time in response to cues from the environment, etc. (Fessenden, 2017). It’s akin to playing the “Six Degrees of Kevin Bacon” game, but with proteins. For many researchers, interactomics could be a powerful tool for precisely understanding how a faulty protein can cause problems in other molecular pathways, which can give rise to diseases (Fessenden, 2017).

Looking at the protein version of the Kevin Bacon game is another reminder of our biological Rube Goldberg machines’ complexity. It is also a wonderful step to a deeper and sounder understanding of the body’s mechanical workings, which could be a boon for precision medicine. To properly tackle the ginormous challenge of generating a sounder understanding, however, will take a massively coordinated effort of the pharmaceutical industry, research community, and medical community.

 

References

Fessenden, M. (2017). Protein maps chart the causes of disease. Nature, 549(7671), 293-295. doi:10.1038/549293a

Kobayashi, Y., & Mitsudomi, T. (2016). Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy. Cancer Sci, 107(9), 1179-1186. doi:10.1111/cas.12996

Kopetz, S., Desai, J., Chan, E., Hecht, J. R., O’Dwyer, P. J., Lee, R. J., . . . Saltz, L. (2010). PLX4032 in metastatic colorectal cancer patients with mutant BRAF tumors. Journal of Clinical Oncology, 28(15_suppl), 3534-3534. doi:10.1200/jco.2010.28.15_suppl.3534

Loeb, K. R., & Loeb, L. A. (2000). Significance of multiple mutations in cancer. Carcinogenesis, 21(3), 379-385.

Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., . . . Bernards, R. (2012). Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature, 483(7387), 100-103. doi:10.1038/nature10868

Sapiezynski, J., Taratula, O., Rodriguez-Rodriguez, L., & Minko, T. (2016). Precision targeted therapy of ovarian cancer. J Control Release, 243, 250-268. doi:10.1016/j.jconrel.2016.10.014

Tomasetti, C., Vogelstein, B., & Parmigiani, G. (2013). Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation. Proc Natl Acad Sci U S A, 110(6), 1999-2004. doi:10.1073/pnas.1221068110

Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., Jr., & Kinzler, K. W. (2013). Cancer genome landscapes. Science, 339(6127), 1546-1558. doi:10.1126/science.1235122

 

SomaLogic closes $200M financing round

Nan Fung Life Sciences and Madryn Asset Management join iCarbonX in investing to accelerate SomaLogic’s unique precision health insights delivery business

January 3, 2018 – Boulder, CO – SomaLogic announced today that it has capped its $200 million funding round, anchored by iCarbonX with substantial investments from Nan Fung Life Sciences and Madryn Asset Management. The successful round will accelerate SomaLogic’s goal of becoming the world’s leading provider of precision digital health insights.

SomaLogic uniquely and precisely measures thousands of human proteins rather than genes, and turns those measurements into insights that empower people to purposefully and meaningfully manage their individual health and wellness. SomaLogic’s “SOMAscan®” technology, which currently measures 5,000 proteins in a single sample, has successfully analyzed over 150,000 samples across more than 50 diseases or conditions, with plans for an additional 1 million more samples by the end of 2020. The continuously growing power of the SOMAscan technology, the massive proprietary data sets being accumulated and analyzed, and the strategy for turning those assets into a successful health insight company have together caught the attention of leading investors in emerging digital health markets.

“We are delighted to expand our relationship with SomaLogic and continue to support the company’s growth,” said Avinash Amin, Managing Partner at Madryn Asset Management. “We believe SomaLogic’s proteomics technology provides the basis for unique and differentiated insights into human health and disease, with broad implications for diagnosis and treatment.”

Understanding the changes over time in bodily proteins is being increasingly recognized by the medical community as essential to the effective personalized maintenance of health and management of disease. Unlike genes, proteins respond dynamically to changes in the body and the environment, offering meaningful and actionable health information in real-time.

“These new investments by Nan Fung and Madryn, two elite, global healthcare investors, are yet another huge vote of confidence in our strategic direction and the deep intrinsic value of our technology,” said Al Reynolds, SomaLogic’s CEO. “We are delighted that they recognize the huge potential of our technology to radically transform healthcare, and are joining us as valued partners to accelerate that goal.”

Specific financial details were not disclosed.

SomaLogic Contact
Laura S. Mizoue, Ph.D.
Communications Specialist
T: 720-417-7509
lmizoue@somalogic.com

About SomaLogic:
SomaLogic delivers meaningful and actionable health-management insights that empower individuals worldwide to continuously optimize their personal health and wellness throughout their lives.
These essential insights, provided through a global network of partners and users, are derived from precise, proprietary, and personalized measurement of critical changes in an individual’s proteins throughout life. For more information, visit http://www.somalogic.com/.

About Nan Fung Group:
Founded in 1954, Nan Fung Group is a conglomerate based in Hong Kong with global interests in real estate development and investment, financial investment, hotels and shipping. The Group continues to diversify its business and growth globally with interests in a diverse range of business partnerships, including life sciences.

About Nan Fung Life Sciences:
Nan Fung Life Sciences, part of Nan Fung Group, is a global life science investment platform with a significant presence in the US and Greater China.
Leveraging on the Group’s strong capital position, it has a long-term commitment to life sciences through direct investments and fund investments covering the full spectrum of the industry (including therapeutics, medical devices and diagnostics) and across different development stages.

About Madryn Asset Management, LP:
Madryn Asset Management, LP is a leading alternative asset management firm that invests in innovative healthcare companies specializing in unique and transformative products, technologies, and services. The firm draws on its extensive and diverse experience spanning the investment management and healthcare industries, and employs an independent research process based on original insights to target attractive economic opportunities that deliver strong risk-adjusted and absolute returns for its limited partners while creating long-term value in support of its portfolio companies. For additional information, please visit www.madrynlp.com.

 

Large-scale profiling of blood proteins identifies new markers of heart damage

A new report published online in the American Heart Association journal Circulation describes the successful measurement of changes in blood proteins at a previously unattainable scale. The results revealed a large number of proteins that increased significantly soon after a heart attack—some that are well-known markers of myocardial damage but many that are completely new. This proof-of-principle study demonstrates that comprehensive protein profiling to diagnose and treat human health and disease is on the horizon.

The types and levels of many proteins that circulate through the body are constantly changing in response to changes in real-time health status. Until recently, this gold mine of information has remained largely untapped because conventional technologies can’t measure thousands of proteins present in vastly different concentrations in complex mixtures such as blood.

In this study, researchers at the Novartis Institute for BioMedical Research, Beth Israel Deaconess Medical Center and Brigham and Women’s Hospital used the SOMAscan platform to measure the levels of ~5,000 proteins in blood samples taken from patients undergoing a “planned” heart attack, a medical procedure that can help reduce severely overgrown heart muscle (hypertrophic cardiomyopathy). They analyzed plasma taken before and at different time points after the procedure, looking for proteins whose levels changed significantly. Their results not only confirmed findings from an earlier study that used an earlier, smaller version of the SOMAscan platform (ref: Ngo, D et al. (2016) “Aptamer-Based Proteomic Profiling Reveals Novel Candidate Biomarkers and Pathways in Cardiovascular Disease.” Circulation 134(4): 270-285.), but also identified nearly 150 new proteins, many of which had not been previously associated with heart damage. Twenty-nine of the proteinswere also elevated in patients who suffered “unplanned” heart attacks.

This article is the first published description of large-scale protein profiling at a level that has not previously been reported. The expanded SOMAscan assay platform provides opportunities for unbiased discovery of disease markers to improve diagnosis, predict future events, monitor responses to therapies and identify targets for drug development. Ongoing studies by these authors are applying this expanded SOMAscan platform to larger groups of patients.

Jacob, J et al. (2017) “Application of Large Scale Aptamer-Based Proteomic Profiling to “Planned” Myocardial Infarctions.” Circulation, epub ahead of print.

Larry Gold named to 2017 National Academy of Inventors

The National Academy of Inventors (NAI) has named Larry Gold, the founder and chairman of the board of SomaLogic, as one of its 2017 fellows.

Election to NAI Fellow status is the highest professional distinction given to academic inventors. NAI Fellows are inventors on U.S. patents and were nominated by their peers for their spirit of innovation and creation of new technologies that have significantly impacted society.

Dr. Gold has been a professor in the department of Molecular, Cellular and Developmental Biology at the University of Colorado, Boulder since 1970 and is an elected fellow of the National Academy of Sciences and the American Academy of Arts and Sciences. A bioscience industry pioneer, Dr. Gold founded two other biotech companies prior to SomaLogic.

The NAI elected 155 fellows to the class of 2017. The induction ceremony will be in April as part of the Seventh Annual NAI conference in Washington, D.C.

 

Click here to read the story from the University of Colorado, Boulder.
Click here for more information on the National Academy of Inventors

An immune system timeline for tuberculosis progression

An international team of researchers has defined the series of immune system changes that occur when tuberculosis (TB) transitions from a non-infectious state to active disease. The results, published online in PLOS pathogens, highlight changes in inflammatory processes that can be detected in the blood long before clinical symptoms arise. These findings have important implications for developing diagnostics, vaccines and treatments to battle the TB epidemic.

An estimated 1.7 billion people—one quarter of the world’s population—are infected with the bacterium that causes TB, but only ~10% develop active pulmonary disease. In the article, scientists from the South African TB Vaccine Initiative, the University of Cape Town, the Center for Infectious Disease Research and SomaLogic looked for changes in various molecules in blood that together could predict the risk of TB progression. The time between the initial blood collection and TB diagnosis ranged from 1 to 894 days, so the investigators could construct a timeline of changes that occurred as the disease evolved.

The blood analyses revealed that TB progression associated with sequential modifications of immunological processes. Some of these processes, such as type I/II interferon signaling and complement cascade, were elevated as early as 18 months before TB diagnosis.

Understanding the biology of progression from infection to active pulmonary TB opens the door to blood-based tests that may determine those who are at risk of developing active disease and who need early treatment. These findings could also help development of better vaccines and host-directed therapies that accelerate eradication of TB infection.

Ref: Scriba, TJ et al. (2017) “Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease”PLOS Pathogens 13(11): e1006687.