Research To The People

Research To The People assists patients who no longer have a "standard of care" and have exhausted their recommended treatment options, including medical treatments, holistic treatments, and clinical trials. Previous patient cases have included rare metastatic cancers, metabolic conditions, genetic diseases, and undiagnosed conditions.

• Cancer alone afflicts approximately 5.5 percent of the US population. Globally the share of people with cancer reached 1.3% in 2017. (https://ourworldindata.org/can...)

• Fewer than 3% of these patients are able to participate in clinical trials (https://www.ncbi.nlm.nih.gov/books/NBK50895/)

• And of those, only 3.5% will have a successful response. (https://www.acsh.org/news/2020...)

• In a population of 330 million, the problem affects more than 500,000 people in the US.

• In a population of 7.8 billion, the problem affects about 12.5 million people globally.

Treatment of this class of illness lacks new and novel research. With our current healthcare system putting much of its funding into symptom management and treatments for commonly occuring conditions, this type of research is often not accessible to patients and when available is not reimbursable with traditional health insurance.

Where RTTP differs from traditional medicine, is our precision medicine focused on the patient and their specific research goals. No one knows a disease like the affected community. By generating and analyzing data specific to unanswered patient questions we put the patient and/or their community at the center of the research. We focus on the pressing questions that most affect the patient’s health and quality of life by bringing the patient, his/her data, and research network teams together in the same room for several days to discuss, analyze, and brainstorm in a hackathon format.

Our solution is to generate cutting-edge research-grade diagnostic testing data for patients at no cost to them. This precision medicine approach to data generation would likely not be accessible to individuals financially. After the data generation, we crowd-source the analytics of that data to a curated list of credentialed research scientists and medical practitioners, who use algorithmic or computer science approaches to integrate the data into a cohesive picture to find molecular explanations for the patient’s suffering. In some cases, we take it a step further, and use these diagnostic findings in tandem with the patient’s clinicians to expand their therapeutic options. 

For our data generation, we use long-read sequencing platforms from Pacific Biosciences or Oxford Nanopore (in a previous partnership with Illumina), Bionano Genomics’ optical genome maps, algorithmic genome assemblers such as Wengan D. 

Collaborative researchers have been affiliated with top institutions such as MIT, Harvard, Stanford, UC Berkeley, UCSF, and The Mayo Clinic. Fields represented include biology, genetics, computer science, bioinformatics, and/or computational biology. 

Our program supports patients who no longer have a "standard of care" and have reached the end of their clinical trial and novel medical options. This impacts their lives by offering patients and their existing medical teams health data sets that would be otherwise unavailable through traditional diagnostics. With more data generated and made available to interdisciplinary researchers and analysts, this solution increases both patient’s chance for finding new novel treatments to increase quality of life and when broadened, information available to researchers who are developing treatments or writing papers to widen understanding of the conditions. 

• Our prior patient demographic has included patients with 1) Rare Cancers, 2) Rare Diseases, 3) Metastatic Cancers and 4) Undiagnosed Conditions.
• Our process starts with a patient application followed by a patient interview.
• Speaking with each applicant individually allows us to better understand their individual needs. We prioritize applications from patients who come from underserved and diverse backgrounds.

The goal for patients with rare cancers is typically to discover off-label therapeutic candidates to slow the progression of disease and increase survivability while with undiagnosed patients, the goal is to get a better understanding of core genetics behind multi-systematic and hard to diagnose physical conditions. Both classes of solutions require us to reach out to our network of researchers and data scientists, let them know the patient history, and describe the -omic data that the patient and his care team have gathered. Often, the data is insufficient, so we partner with sequencing companies and universities to generate new data as required. Critical to the process is developing a close relationship with every patient as well as their support network. Here are some examples of the way we’ve presented past patient’s cases. https://www.researchtothepeople.org/cases or https://rttp.stanford.edu/

• Each case is individual, as is each set of needs and results provided. 
• During Onno’s case, a team identified an off-label use of Lapatinib. In John’s (Undiagnosed-1) case, one team discovered a TNXB mutation. In Bill’s case, he discovered a team willing to work with him and is exploring two different therapeutics.  For Bill, each of his hackathons resulted in peer reviewed papers, which he has been able to use to gain more interest in his personal case, and offers future researchers more resources to cite while applying for funding for research to help future patients with the same diagnoses. 

Research To The People is uniquely suited to this solution from our core development team to our external research collaborators. At the heart of our organization is our principal investigator Dr. Michael Synder who currently sits as Chair for Stanford Medical School’s Department of Genetics and the Director of Stanford’s Center for Genomics and Personalized Medicine. Dr. Snyder is a leader in the field of functional genomics and proteomics. As a major developer of the ENCODE project, hosted by Stanford Medical School and funded by the National Human Genome Research Institute, Dr. Snyder has experience taking breakthrough research pilot projects and turning them into global scale initiatives. With his decades of professional experience in the field and experience developing a pilot project into an international large-scale initiative such as ENCODE, and headquartered at the world renowned research institution Stanford Medical School, RTTP has strong collaborations with industry powerhouses such as Alexion Pharmaceuticals, Google, and Ilumina. Combining and utilizing the best of both academic and Industry standards, RTTP builds strong interdisciplinary research teams to offer patients quality diagnostics and data analyses no matter their financial, demographic, or geographical limitations.

We are applying to the Horizon Prize Challenge because we hope to bring our program into the Horizon Therapeutics and MIT ecosystem, fund more patient cases, collaboratively engage researchers and engineers in Boston, and produce more open science. We could not have achieved everything we have without institutions like Alexion and Stanford. We admire how Horizon Therapeutics is dedicated to putting rare disease patients first through advocacy, education, and bringing medicines for those with unmet needs. As an organization that also puts patients first and is working on a variety of illnesses, we see potential in hosting hackathons in diseases that Horizon Therapeutics targets, including chronic granulomatous disease, nephropathic cystinosis, and thyroid eye disease, amongst many other ways we could collaborate.

We also have so much to learn from the Solve program and other participants. We see MIT Solve as more than just an initiative, it’s a community of social entrepreneurs making incredible progress - seeing high value partnerships across all industries between members and solvers, like Beyond conflict’s partnership with Twilio and MediCapt and the Patrick J. McGovern Foundation demonstrates the ability of the ecosystem to produce these quality relationships. We also know that as a younger organization just entering our growth stage, we have a lot to learn from other Solvers' experiences both within our challenge and outside. As we expand our program across the world in the next five years, having the diverse worldwide MIT Solve network will be invaluable.

This program is the true realization of the Precision Medicine Initiative. The key is in the combination of advanced research technologies (Oxford Nanopore, Bionano Genomics, and Pacific Biosciences) to eliminate sequence gaps in patient genomes, providing clarity and contiguity impossible with previous technologies. Currently, Illumina’s short-read sequencing technology has a 30% diagnostic yield [Dr. Bick, HudsonAlpha Institute for Biotechnology]. It is estimated that ten percent of the U.S. population have a rare disease [National Organization for Rare Diseases, 2021], which leaves over 20 million people searching for diagnostic answers in the USA alone.  

1. Our solution is innovative through the use of technology’s unique ability to generate unbiased patient specific genomic data, minimizing data loss, making the diagnostic phase as precise and accurate as possible.

2. Our solution incorporates crowd-sourcing, networking and coordination of researchers with interest in the relevant patient cohorts. These researchers often employ artificial intelligence or machine-learning algorithms to analyze vast amounts of information quickly.

3. Our solution is innovative due to the speed and accuracy of data analyses when compared to traditional genetic research. This increase in processing speed allows rare disease and cancer communities to spend less time in the diagnostic stage allowing for more time to be spent on finding solutions to increase quality of life, in disease where time is limited, decreased data generation can be lifesaving. We believe a paradigm shift is needed, and that our precision medicine approach not only benefits the patient but expands existing knowledge of rare conditions for their greater community. 

For 2022-2023, we are running a 100 patient first of its kind study for Hypophosphatasia, a rare metabolic bone disease. This study will examine the link between oral and gut microbiome and Hypophosphatasia, utilizing whole genome sequencing. This project is unique because it will allow us to return real time insights to patients on how to better manage their symptoms and overall health.

In 2023 we are bringing four more rare cancer patients into our program. This cohort will be extensively profiled including: WGS, RNA, Proteomics, Immune Cell / Cytof/ CodeX, Single cell Multi-Omics, Neoantigen analysis, Cytokines, Metabolomics, and Microbiome-Immune system analysis.

We are measuring our progress toward our goals of working with more patients and increasing the number of sites offering the Research to the People program by looking at the raw number of patients we have worked with, the amount of data we are able to make available to patient communities and researchers, and the number of peer reveiwed papers that are published using our generated data. Our program relies on a worldwide network of scientists and researchers, offering turn-key connections at top institutions around the world. In addition to adding more sites, our natural expansion focuses on scaling the number of patients we’re able to serve. Having well documented processes and procedures will allow us to expand access for patient participants and run efficiently. 

RTTP's solution specifically addresses the unjust burden of rare diseases faced by disinvested communities and historically underrepresented identity groups. This is done by specifically selecting these patients for our program. We promote community and connection among rare disease patients and their advocates by supporting them, progressing relevant research through data generation for their specific cases, forming a scientific team to analyze their cases, and bringing together scientific supporters at our hackathons. We unlock collaboration among patients, scientists, and health care providers to improve patient outcomes and leverage big data and analytics to improve the detection and diagnosis of rare diseases at our hackathons and provide real time feedback on possilble causes to their symptoms leading to better symptom management and quality of life. Our impact continues to grow beyond the individual patient by increasing data available to researchers and health care providers to help more patients with the same conditions in the future. 

RTTP Utilizes several types of technology to power our solution. With the recent completion of Chromosome X and 8 using a combinatorial approach, with Oxford Nanopore & Pacific Biosciences data to look for large structural changes, and Optical Genome Map as a scaffold for accurate assembly, contiguous, even telomere-to-telomere genome assembly has been made possible, which will illuminate sequence gaps and repetitive regions, where many rare diseases lurk.  Many rare disease and cancer patients are unable to get diagnoses due to these dark areas. 

Currently, commercially available ion torrent and Illumina sequencers operate by chopping up the 3.2 billion base pairs in our genome into segments of only 150bp long, sequences them, and reassembles them in a computer. The problem with this is that some areas are very repetitive, and when the computer is confused about where to put two pieces that are identical, that data is often dropped, and a hole emerges in the genome assembled from these smaller segments. What we do is incorporate long-read sequencing (more distinct, longer segments), the same technology that enabled gapless assemblies of Chromosomes X and 8. We use AI algorithms to assemble that genome with the highest fidelity, and then we take that assembled genome and make it available to multiple interested parties who have been developing diagnostic software to run on that assembled genome. This makes it so that the patient gets a premium genome and multiple diagnostic approaches on their data.

RTTP prides itself for it's incredibly diverse leadership team. At our core, RTTP is by rare disease patients, for rare disease patients. Amongst leadership includes rare disease patients, women, people of color, and LGBTQ+ community members. At current, 90% of RTTP's core leadership team identifies in one of these categories. 

RTTP's business model sits at the intersection of basic science research, translational medicine and patient care. We plan to implement business model elements from each of these verticals into our strategy. Our program is currently grant funded with strong early support from academia, biotech and pharma. 

 As we refine our ability to deliver results and better quantify how we are impacting patient lives we expect to be able to fall back on traditional healthcare business models. Although far from optimal, and hardly desirable, traditional healthcare business models could be the most sustainable route for growth.

 Our preferred business model is inventing something new that has never been done before. In the spirit of building a new system for patients engaging in research medicine, we feel most enthusiastic about this route. We're optimistic about this unknown, due to the pace of change we have seen from patients, and cultural shifts in science and medicine.

 Alternatively, Research to the People has been approached with the opportunity to work with multiple self funded patients who can afford to pay out of pocket for all expenses. In the future we intend to take on a number of these cases to support growth and support our mission of working with patients who are less financially privileged.

RTTP is raising funding as an independent 501(c)(3) non-profit and as an academic program based at Stanford University School of Medicine. Our first 3.5 years were supported with less than $50k. We relied on donated sequencing data generation and an extensive network of volunteers. 

In 2020 we raised a $250k grant for our Hypophosphatasia case. This funding will support data generation, staffing and infrastructure. 

In the next year we hope to complete a $500k - $2m raise to switch to an annual funding model and expand the number of patients we're able to work with. In the next five years we hope to raise $20m for operations for the next 10 years.

Our goal is to be able to invest about $20k - 200k in data generation per rare disease patient case, which will include a small patient cohort for comparative data purposes.

Our program currently works with patients for free and there is no cost for a patient to participate.

At current we have received the following support:

•  A $250,000 grant for our Hypophosphatasia case in 2020. This funding will support data generation, staffing and infrastructure and was sponsored by Alexion Pharmacuticals. 
• Google Cloud: $150,000 in cloud credits
• Mayo Clinic: estimated $10,000 in-kind research analysis 
• Personalis: estimated$40,000 in-kind Data Generation 
• Teiko Bio: Estimated $20,000 in-kind Data Generation 
• Illumina: Estimated $5,000 in-kind research analysis
•  UMN Medical School: Estimated $20,000 in-kind data generation and research analysis 
• UCLA Health: Estimated $2,000 in-kind oncology support 
• CureMatch: Estimated $5,000 in-kind research analysis 
• Omicure: Estimated $5,000 in-kind research analysis