By Ben Butkus
Telome Health, a Menlo Park, Calif.-based company using quantitative PCR to measure telomere length from tissue samples for research, drug-development, and health-monitoring applications, emerged from stealth mode this week, disclosing details about its technology platform and upcoming business activities.
With some of the field's pre-eminent experts in telomere biology onboard, the startup is banking on the notion that recent scientific studies correlating the length of telomeres, the protective caps at the ends of chromosomes, with health status, disease, mortality risk, and drug response will translate into a viable business model in which Telome Health provides this data from assays conducted in house.
The very breadth of potential applications of telomere biology, however, present challenges for Telome Health as it begins to zero in on exactly which applications will prove most fruitful in the short term.
"Because the telomere is such a fundamental part of human biology, there are a lot of applications," Telome Health CEO Dan Hunt told PCR Insider this week. "There are so many studies coming out that show correlations between telomere length and various phenomena, that there are a lot of different ways we can go with this."
Telome Health was formally founded around May of last year by a few individuals, including Elizabeth Blackburn, a professor at the University of California, San Francisco, and winner of the 2009 Nobel prize in Physiology or Medicine for her work on telomere structure and function and discovery of telomerase; and Calvin Harley, a former Geron scientist credited with linking telomeres and telomerase to human cell aging and disease.
Blackburn currently chairs Telome Health's scientific and clinical advisory board; while Harley serves as chief scientific officer at the company.
Soon after its founding, Telome Health raised about $650,000 from several undisclosed private investors; and in the late summer Hunt joined the company to provide business and commercial guidance.
One of Hunt's key tasks was securing a worldwide exclusive license to intellectual property developed by Richard Cawthon at the University of Utah, including a seminal patent surrounding the use of qPCR to measure telomere length.
Cawthon told PCR Insider this week that the unique aspect of the method is a special primer design that sidesteps the difficulties associated with priming the signature telomeric sequences, which are hexamer repeats.
"The question was, 'How can you make both primers be based on the repeat, and yet [not] a problem with primer-dimer formation?' You would think that since they are both based on the same repeat that they must hybridize to each other, and indeed they do; but I purposely introduced mutations every sixth base, so that the 3' ends of each primer would always … be mismatched against the other primer."
Cawthon's original method, developed in the early 2000s, used multiwall SYBR Green-based qPCR; however, in 2009 he published an improved method that uses multiplexed SYBR Green PCR. This method, which Cawthon calls monochrome multiplex qPCR, is patent-pending and can be used "more generally than just measuring telomeres," he said. Telome Health has also licensed this patent application as part of its IP bundle from the University of Utah, Cawthon said.
Cawthon also pointed out that the method "only gives you a measure of average telomere length" and won't show the distribution of the longest and shortest telomeres in a sample.
According to Telome Health's Hunt, the PCR methodology "has been used in several thousand published papers where people are measuring mean telomere length. So in terms of our method, it's not remarkably different from what's currently being used, and I think that's a positive thing, because a lot of the data other people have produced about telomere length should be relevant in comparing the data we get."
Telome Health's IP portfolio also contains patents related to uses of the data obtained from such qPCR assays, Brown noted.
In a statement, Telome Health's Harley called the technology "scalable and cost-effective," and said that the company believes it will be "the dominant technology for high-throughput assays and a key competitive advantage for Telome Health in our field."
After securing its initial IP portfolio, Telome Health began discussing potential collaborations with companies in various industries, a process that shed some light on the potential application areas for telomere length measurements.
"In the short term [we are focusing on] partnering with personalized health or consumer health companies," Brown said, alluding to one such company that he anticipated striking a deal with "very soon."
The undisclosed company "was founded by a pretty well-known team … to provide health information to people," Brown said. "Their approach is to basically do a genomic screen on people, similar to what 23andMe does; but to also integrate that with monitoring their daily routine and guiding them on various things — maybe what nutritional supplements they want to take, what their exercise regimen is."
The upshot would be a personalized medicine profile, of sorts, into which information about telomere length would be integrated.
Brown said that the company has also begun discussions with various wellness experts and groups that might be interested in learning how a patient's telomere length might play into their health.
"The other thing we'll probably get into, but a little further down the road, is trying to integrate telomere length measurements into healthcare management for people who are actually pretty sick," Brown said.
As an example, he cited studies demonstrating that people with congestive heart failure or pneumonia and very short telomeres have greatly increased risk of morbidity and mortality.
"So we think that there are many uses here for telomere lengths, which may help doctors …monitor those patients more carefully, and maybe triage these people to see who needs the most intervention; or even help them make decisions about when people might be released from the hospital," Brown said.
Lastly, Brown said that a pharmacogenomic link has been made between telomere length and patients' response to certain therapies, in particular antidepressants. For instance, "we know that people who have depression with short telomeres respond to SSRIs more than people who have long telomeres," Brown said. "And so you could envision … us making overtures to companies making antidepressants, to see if they can incorporate that into their selection criteria in their clinical plans."
Telome Health said that it is currently accepting requests from academic, pharmaceutical, and corporate research groups to assay telomere length in patient samples, with health monitoring testing planned for the second half of this year.
Currently, Telome Health's assays would survey for telomere length in a patient's blood sample, although the company is working on a method that would allow testing of other bodily fluids, such as saliva.
Telome Health currently has just shy of a dozen employees and has office and lab space in Menlo Park. Brown said that the company is "always open to raising money. I think, as always, that it's just a matter of terms. He added that Telome Health raised its first funds through a convertible debt offering, which is most likely the route it would take at this point in time.
"Generally what you'd like to do is drive up the valuation before you have an equity financing, and I think we'd like to do that," he said. "But we're pretty open to various structures and we've been in discussions with various people about different approaches to financing."
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