With $191 million in startup capital, the genomics startup will draw on existing genetic databases to create personalized medicine therapies for chronic diseases
Why do some people get sick while others do not? That’s what genetic researchers at Maze Therapeutics want to find out. They have developed a new approach to using tools such as CRISPR gene editing to identify and manipulate proteins in genetic code that may be the key to providing personalized protection against specific diseases.
If viable, the results of Maze’s research could mean the development of specific drugs designed to mimic genetic code in a way that is uniquely therapeutic to specific patients. This also would create the need for clinical laboratories to sequence and analyze patients’ DNA to determine whether a patient would be a candidate for any new therapies that come from this line of research.
Based in San Francisco, Maze Therapeutics (Maze) is studying modifier genes—genes that affect the phenotype or physical properties of other genes—and attempting to create drugs that replicate them, reported MIT Technology Review. Maze believes that genetic modifiers could afford a “natural form of protection” against disease.
“If you have a disease-causing gene, and I have the disease-causing gene, why is it that you may be healthy and I may be sick? Are there other genes that come into play that provide a protective effect? Is there a drugging strategy to recover normal phenotype and recover from the illness?” Maze Chief Executive Officer Jason Coloma, PhD, asked in an interview with FierceBiotech.
In 2019, Maze received $191 million in financing from Third Rock Ventures, ARCH Venture Partners, and others, to find ways to translate their findings into personalized medicines, according to a news release. And with the availability of international public genetic databases and CRISPR gene editing, now may be good timing.
“This was the perfect time to get into this space with the tools that were being developed and the amount of data that has been accumulated on the human genetic side,” Charles Homcy, MD, Third Rock Ventures Partner and Maze Scientific Founder, told Forbes, which noted that Maze is tapping existing population-wide genetic databases and large-scale studies, including the United Kingdom’s Biobank and Finland’s Finngen.
To help find genetic modifier drug targets, Maze is accessing CRISPR gene editing capabilities. Jonathan Weissman, PhD, Maze Scientific Founder and Professor of Cellular Molecular Pharmacology at University of California, San Francisco (UCSF), told MIT Technology Review: “You take a cell with a disease-causing gene and then see if you can turn it back to normal. We can do 100,000 experiments at once because each cell is its own experiment.”
“At Maze, we are focused on expanding our understanding of the natural disease protection provided by genetic modifiers through an integrated approach that combines studying natural human genetic variation across the globe and conducting large-scale experiments of gene perturbations,” Charles Homcy, MD (above), Founder and interim CEO of Maze and a partner at Third Rock Ventures, said in a news release. “Through our integrated approach, we believe we will create novel medicines based around those modifiers to treat a number of diseases.” (Photo copyright: Forbes.)
Using CRISPR to Identify the Cause of Disease
One drug research program reportedly progressing at Maze involves developing gene therapy for the neurogenerative disease amyotrophic lateral sclerosis (ALS). The program borrows from previous research conducted by Aaron Gitler, PhD, Professor of Genetics at Stanford University and Maze co-founder, which used CRISPR to find genetic modifiers of ALS. The scientists found that when they removed the protein coding gene TMX2 (Thioredoxin Related Transmembrane Protein 2), the toxicity of proteins building the disease was reduced, reported Chemical and Engineering News.
“We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells,” Gitler and colleagues wrote in Nature Genetics. “Together, our results demonstrate the promise of using CRISPR-Cas9 screens in defining the mechanisms of neurodegenerative diseases.”
“We have the flexibility to think differently. We like to
think of ourselves as part of this new breed of biotech companies,” Coloma told
FierceBiotech.
It’s an exciting time. Clinical laboratories can look
forward to new precision medicine diagnostic tests to detect disease and
monitor the effects of patient therapies. And the research initiatives by Maze
and other genetic companies represent a new approach in the use of genetic code
to create specific drug therapies targeted at specific diseases that work best
for specific patients.
The companion diagnostics that may come from this research would
be a boon to anatomic pathology.
Expanded ‘Cancer Gene Census’ is expected to accelerate development of new therapeutics and biomarker-based personalized medicine diagnostic tests for disease; could be useful for anatomic pathologists
Oncology is one of the fastest-developing fields in precision medicine and use of DNA-based diagnostics. Surgical pathologists are helping many cancer patients benefit from the use of a companion genetic test that shows their tumors are likely to respond to a specific drug or therapy. Consistent with that work, researchers in the United Kingdom (UK) have now produced the first comprehensive summary of all genes known to be strongly associated with cancer in humans.
The expansion of the “Cancer Gene Census” is noteworthy for anatomic pathologists who should expect to see the information increase the understanding of cancer causes and accelerate the development of new therapeutics and biomarker-based molecular diagnostics.
In this latest Cancer Gene Census, researchers from the Wellcome Sanger Institute (WSI) used CRISPR gene editing systems to produce an expanded catalog of 719 cancer-driving genes in humans.
According to a review article on the project published in Nature Reviews Cancer, “The recent expansion includes functional and mechanistic descriptions of how each gene contributes to disease generation in terms of the key cancer hallmarks and the impact of mutations on gene and protein function.”
The 2018 Cancer Gene Census from the Wellcome Sanger Institute in the United Kingdom summarizes 719 genes suspected of causing cancer in humans and describes how they function across all forms of the disease. (Photo copyright: Wellcome Sanger Institute.)
The Catalogue of Somatic Mutations in Cancer (COSMIC) provided the foundation for the WSI’s research. It involved manually condensing almost 2,000 research papers to develop evidence for a gene’s role in cancer.
While the COSMIC database characterizes more than 1,500
forms of human cancer and types of mutations, the U.K.’s Cancer Gene Census
goes further and “describes which genes are fundamentally involved and
describes how these genes cause disease,” a Wellcome Sanger Institute news
release states.
“For the first time ever, functional changes to these genes
are summarized in terms of the 10 cancer hallmarks—biological processes that
drive cancer,” the statement explains. “Mutations in some genes lead to errors
in repairing DNA, whereas mutations in other genes can suppress the immune
system or promote tumor invasion or spreading. Across the 700 genes in the
Cancer Gene Census, many have two or more different ways of causing cancer.”
Zbyslaw Sondka,
PhD, lead author on the WSI project, believes their study has provided
scientists with much needed new insights. “Scientific literature is very compartmentalized.
With the Cancer Gene Census, we’re breaking down all those compartments and
putting everything together to reveal the full complexity of cancer genetics,” he
noted in a WSI
article.
“This is the broadest and most detailed review of human
cancer genes and their functions ever created and will be continually updated
and expanded to keep it at the forefront of cancer genetics research,” Sondka
added.
Making Precision
Medicine More Precise
An understanding of the roles played by different genes in
various cancers is key to enabling researchers to develop drugs that will be
effective against individual cancers.
“The combination of the Cancer Gene Census with COSMIC will
enable researchers to investigate individual mutations and try to find good
targets for anti-cancer drugs based on the actual processes involved,” Simon Forbes, PhD,
Senior Author of the Cancer Gene Census paper and Director of COSMIC at the
Wellcome Sanger Institute, stated in the WSI news release.
Simon Forbes, PhD (above), Director of COSMIC at the Wellcome Sanger Institute and Senior Author of the Cancer Gene Census paper, believes the institute’s latest Cancer Gene Census, which catalogs 719 cancer-causing genes, will “help make precision medicine even more precise” by allowing “biologists and pharmaceutical scientists to see patterns and target particular pathways with anti-cancer drugs, not solely single genes.” (Photo copyright: Wellcome Sanger Institute.)
The path to precision medicine cancer treatments was further boosted this month when Wellcome Sanger Institute researchers, in partnership with the Open Targets Platform, announced a new system to prioritize and rank 600 drug targets that show the most promise for development into cancer treatments, noted a WSI statement.
The WSI/Open Targets team published its research in the international science journal Nature.
CRISPR-Cas9 and
Personalized Medicine
This latest research springboards off one of the largest CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 screens of cancer genes to date. Researchers used CRISPR gene-editing systems to disrupt every gene within 30 different types of cancers and locate several thousand key genes essential for cancer’s survival. They then identified 600 genes that potentially could be used in personalized medicine treatments.
“The results bring researchers one step closer to producing
the Cancer
Dependency Map, a detailed rulebook of precision cancer treatments to help
more patients receive effective therapies,” the Wellcome Sanger Institute statement
notes.
Anatomic pathologists and clinical laboratories should note
the speed at which development of useful biomarkers for diagnosing cancer is
progressing. All labs will want to be prepared to capitalize on those
advancements through the lab testing services they offer in their medical laboratories.
New McKinsey report offers three market trends that could help clinical laboratories position themselves as front-runners in the race toward precision medicine With federal Medicare reporting and reimbursement programs now weighted heavily toward precision medicine practices that involve genetic testing to reveal predispositions to certain diseases, the trend is widely recognized as the future of U.S. healthcare. But are clinical laboratories and anatomic pathology groups prepared to take...
Clinical laboratory leaders aiming for patient-centered care and precision medicine outcomes need to acknowledge that patients do not want to be in hospitals or travel to physician offices and patient care centers for blood tests. It can be inconvenient, sometimes costly, and often painful.
That’s why disease management methods such as remote patient monitoring are appealing to many people. It’s a big market estimated to reach $1 billion by 2020, according to a Transparency MarketResearch Report. The study also associated popularity of devices such as heart rate and respiratory rate monitors with economic pressures of unnecessary hospital readmissions.
But can remote patient monitoring be used for more than to check heart rates, monitor blood glucose, and track activity levels? Could such technology be effectively leveraged by medical laboratories for remote blood sampling?
Microsampling versus Dried Blood Collecting
Remote patient monitoring must be able to address a large number of diseases and chronic health conditions for it to continue to expand and gain acceptance as a viable way to care for patients in different settings outside of hospitals. However, as most clinical pathologists and laboratory scientists know, clinical laboratory testing has an essential role in patient monitoring. Thus, there is the need for a way to collect blood and other relevant samples from patients in these remote settings.
One promising approach is the development of new microsampling technology that can overcome past obstacles of dried blood collection. Furthermore, microsampling-enabled devices can make it possible for medical laboratories to reach out to the homebound to secure accurate and volumetrically appropriate samples in a cost-effective manner.
“One well-established fact in today’s healthcare system is that an ever-greater proportion of patients want clinical care that is less invasive and less intrusive,” noted Robert Michel, Editor-in-Chief of Dark Daily and The Dark Report. “Patients want to take more control over their treatment and be more effective at maintaining the stability of their chronic conditions, and often are happier than those who need to travel to have chronic conditions monitored. To meet this need there has been significant innovation, particularly in the area of remote blood sampling using microsampling technology.”
For decades, medical laboratories have tried various methods for acquiring and transporting blood samples from remote locations. One such non-invasive alternative to venipuncture is called dried blood spot (DBS) collecting. It involves placing a fingerprick of blood on filter paper and allowing it to dry prior to transport to the lab.
But DBS collected bio samples often do not contain enough hematocrit (volume percentage of red blood cells) for laboratories and clinical pathologists to provide accurate reports and interpretations. Reported reasons DBS cards have not penetrated a wide market include:
Hematocrit bias or effect;
Costly card punching and automation equipment; and,
Possible disruption to existing lab workflows.
Microsampling Technology Enables Collection of Appropriate Samples
Microsampling has to have the capability to enable labs to deliver quality results from reliable blood samples. This remote sampling technology makes it possible for phlebotomists to offer a comfortable collection alternative for homebound patients and rural residents. It also can be useful for physicians stationed in remote areas. Patients themselves can even collect their own blood samples.
Volumetric Absorptive Microsampling (VAMS) technology enables accurate samples of blood or other fluids from amounts as small as 10, 20, or 30 microliters, according to Neoteryx, LLC, of Torrance, Calif., the developer of VAMS. The technology is integrated into the company’s Mitra microsampler blood collection devices (shown above) in formats for patient use and for medical laboratory microsample accessioning and extraction. Click here to watch a video on the Mitra Microsampler Specimen Collection Device. (Photo copyright: Neoteryx.)
One company developing these types of products is Neoteryx, LLC, of Torrance, Calif. It develops, manufactures, and distributes microsampling products. Patients with the company’s Mitra device use a lancet to puncture their skin and draw a small amount of blood, collect it on the device’s absorptive tip, and then mail the samples to a blood lab for testing (Neoteryx does not perform testing).
“Technologies such VAMS are driving [precision medicine] in an extremely cost-effective manner, while only requiring minimal patient effort. Patients are taking a more active role in their healthcare journeys, and at-home sampling is supporting this shift,” stated Fasha Mahjoor, Chief Executive Officer, Neoteryx, in a blog post. (Photo copyright: Neoteryx.)
Advantages of Microsampling
Patient satisfaction survey data collected by Neoteryx suggest patients are comfortable with their role in blood collection:
70% are comfortable or very comfortable with the process;
86% say it is easy or very easy to use the Mitra device;
92% report it is easy to capture blood on the device’s tip;
55% of Mitra device users are likely or very likely to choose microsampling over traditional venipuncture; and,
93% noted they are likely or very likely to choose the device for child care.
A list of published studies describes certain advantages of VAMS technology that have implications for medical laboratories and clinical pathologists:
Microsampling has benefits and implications for therapeutic drug monitoring, infectious disease research, and remote specimen collection;
Dried blood microsamples from fingerstick can generate reliable data “correlating” to traditional blood collection processes;
Bioanalytical data collected with the Mitra device are accurate and dependable; and,
In a study for a panel of anti-epileptic drugs, VAMS led to optimized extraction efficiency above 86%, which means there was no hematocrit bias.
Learn More by Requesting the Dark Daily Microsampling White Paper
Rise of patient-centered care and remote patient monitoring;
Dried blood collection over the years and the hematocrit effect;
A look at microsampling and how it takes blood collection out of the clinic;
How Volumetric Absorptive Microsampling (VAMS) technology works;
Patient satisfaction data;
Research about microsampling including extensive graphics;
Launching new VAMS technology; and,
Frequently asked questions.
Innovative medical laboratory leaders who want to increase their understanding of how microsampling technology and remote patient monitoring relates to the goal of becoming a patient-centered lab are encouraged to request a copy of the white paper. It can be downloaded at no cost by clicking here, or placing https://www.darkdaily.com/how-to-create-a-patient-centered-lab-with-breakthrough-blood-collection-technology-9-2018/ into your browser.
Both health systems will use their EHRs to track genetic testing data and plan to bring genetic data to primary care physicians
Clinical laboratories and pathology groups face a big challenge in how to get appropriate genetic and molecular data into electronic health record (EHR) systems in ways that are helpful for physicians. Precision medicine faces many barriers and this is one of the biggest. Aside from the sheer enormity of the data, there’s the question of making it useful and accessible for patient care. Thus, when two major healthcare systems resolve to accomplish this with their EHRs, laboratory managers and pathologists should take notice.
NorthShore University HealthSystem in Illinois and Geisinger Health System in Pennsylvania and New Jersey are working to make genetic testing part of primary care. And both reached similar conclusions regarding the best way for primary care physicians to make use of the information.
At NorthShore, two genetic testing programs—MedClueRx and the Genetic and Wellness Assessment—provide doctors with more information about how their patients metabolize certain drugs and whether or not their medical and family histories suggest they need further, more specific genetic testing.
“We’re not trying to make all of our primary care physicians into genomic experts. That is a difficult strategy that really isn’t scalable. But we’re giving them enough tools to help them feel comfortable,” Peter Hulick, MD, Director of the Center for Personalized Medicine at NorthShore, told Healthcare IT News.
Conversely, Geisinger has made genomic testing an automated part of primary care. When patients visit their primary care physicians, they are asked to sign a release and undergo whole genome sequencing. An article in For the Record describes Geisinger’s program:
“The American College of Medical Genetics and Genomics classifies 59 genes as clinically actionable, with an additional 21 others recommended by Geisinger. If a pathogenic or likely pathogenic variant is found in one of those 80 genes, the patient and the primary care provider are notified.”
William Andrew Faucett (left) is Director of Policy and Education, Office of the Chief Scientific Officer at Geisinger Health; and Peter Hulick, MD (right), is Director of the Center for Personalized Medicine at NorthShore University HealthSystem. Both are leading programs at their respective healthcare networks to improve precision medicine and primary care by including genetic testing data and accessibility to it in their patients’ EHRs. (Photo copyrights: Geisinger/NorthShore University HealthSystem.)
The EHR as the Way to Access Genetic Test Results
Both NorthShore and Geisinger selected their EHRs for making important genetic information accessible to primary care physicians, as well as an avenue for tracking that information over time.
Hulick told Healthcare IT News that NorthShore decided to make small changes to their existing Epic EHR that would enable seemingly simple but actually complex actions to take place. For example, tracking the results of a genetic test within the EHR. According to Hulick, making the genetic test results trackable creates a “variant repository,” also known as a Clinical Data Repository.
“Once you have that, you can start to link it to other information that’s known about the patient: family history status, etc.,” he explained. “And you can start to build an infrastructure around it and use some of the tools for clinical decision support that are used in other areas: drug/drug interactions, reminders for flu vaccinations, and you can start to build on those decision support tools but apply them to genomics.”
Like NorthShore, Geisinger is also using its EHR to make genetic testing information available to primary care physician when a problem variant is identified. They use EHR products from both Epic and Cerner and are working with both companies to streamline and simplify the processes related to genetic testing. When a potentially problematic variant is found, it is listed in the EHR’s problem list, similar to other health issues.
Geisinger has developed a reporting system called GenomeCOMPASS, which notifies patients of their results and provides related information. It also enables patients to connect with a geneticist. GenomeCOMPASS has a physician-facing side where primary care doctors receive the results and have access to more information.
Andrew Faucett, Senior Investigator (Professor) and Director of Policy and Education, Office of the Chief Scientific Officer at Geisinger, compares the interpretation of genetic testing to any other kind of medical testing. “If a patient gets an MRI, the primary care physicians doesn’t interpret it—the radiologist does,” adding, “Doctors want to help patients follow the recommendations of the experts,” he told For the Record.
The Unknown Factor
Even though researchers regularly make new discoveries in genomics, physicians practicing today have had little, if any, training on how to incorporate genetics into their patients’ care. Combine that lack of knowledge and training with the current lack of EHR interoperability and the challenges in using genetic testing for precision medicine multiply to a staggering degree.
One thing that is certain: the scientific community will continue to gather knowledge that can be applied to improving the health of patients. Medical pathology laboratories will play a critical role in both testing and helping ensure results are useful and accessible, now and in the future.
