Creating a blueprint for rare disease medicine

blueprint for rare disease medicinePresident Obama’s Precision Medicine Initiative, first laid out in his 2015 State of Union Address, aims to develop individualized care that empowers patients and takes into account genetic, environmental and lifestyle differences. Obama is asking Congress for $309 million for the initiative next year.

One big component is the Department of Veteran Affairs’ Million Veteran Program, which has signed up more than 450,000 veterans to date and is now open to active-duty military personnel. Another is NIH support for cancer trials that match treatments with patients’ genomic profiles.

Parent/citizen scientist Matt Might has in mind another group: patients with undiagnosed genetic disorders. In searching for a diagnosis for his son Bertrand, Might came up with a precision medicine algorithm that outlines step by step what a patient and family can do — from genomic sequencing to finding similar patients to working with biomedical researchers to find therapeutic strategies. It’s an impressively comprehensive blueprint for citizen science.

As Might detailed today at a White House summit on the Precision Medicine Initiative, he now has worms at the University of Utah modeling his son’s disease, whose symptoms include seizures, extreme developmental delay and an inability to make tears. He also has a molecular target and a list of 70 compounds that hit it, including 14 that are already approved by the FDA.

Can Might’s vision be scaled and made part of routine medical care, keeping the patient front and center?

Currently, says Might, “patients are required to navigate the Byzantine academic-industrial complex on their own, with little to no resources for figuring out either what to do or how to do it. We can and must do better.”

Matthew Might at PMI summit precision medicine
Citizen scientist Matt Might wants to scale up what he did for his son in a way that’s scalable, rapid and empowers patients.

Isaac Kohane, MD, PhD, chair of the Department of Biomedical Informatics (DBMI) at Harvard Medical School (HMS), shared Might’s vision. In particular, he saw the potential for bioinformatics and Big Data to quickly identify viable treatment options by crunching patient clinical and genomic data against the scientific, medical and pharmaceutical literature.

Kohane invited Might to come to HMS as visiting professor. “The only possible answer to that question was yes,” Might told the White House audience today. Taking a sabbatical from his day job (as a professor in the School of Computing at the University of Utah), Might joined Kohane in Boston to figure out how to scale up what he’d done for Bertrand.

The Patient-Empowered Precision Medicine Alliance

Alan Beggs, PhD, director of Boston Children’s Manton Center for Orphan Disease Research, also shared Might’s vision and offered his deep and broad expertise in rare and undiagnosed diseases. The team also tapped the pharmacy and genomics expertise of the College of Pharmacy at the University of Utah and the rapid drug-screening capabilities of two industry partners: Recursion Pharmaceuticals and Pairnomix LLC.

The new Patient-Empowered Precision Medicine Alliance, led by Might, was born. It is one of more than 40 commitments from companies, nonprofits, universities, patient advocacy organizations and health care systems to help accelerate the Precision Medicine Initiative.

President Obama Precision Medicine Initiative
“We could accelerate the process of discovering cures in ways that we’ve never seen before,” President Obama said of the Precision Medicine Initiative.

The Alliance is structured to work with patients to craft and execute research and care plans that go from diagnosis all the way to therapy. The ultimate goal is to create an infrastructure for delivering patient-centered precision medicine that could be used in any clinic or hospital.

“We can now rapidly identify the mutations responsible for many rare or ‘orphan’ diseases,” says Beggs. “The challenge now is to quickly turn these discoveries into targeted treatments through partnerships among geneticists, biochemists, pharmacologists and, most importantly, patients and their families.”

Repurposing existing drugs for rare disease

Applying Might’s algorithm to selected genetic disorders, the Alliance aims to match patients’ genetic disorders with existing therapies within 12 months. This will entail pinpointing molecular targets, doing experiments and drug screens in model animals and the patient’s own cells and finally applying bioinformatics algorithms to analyze data sources and tease out therapeutic leads.

“Drug development from scratch is too costly to even begin to address our patients’ needs,” says Kohane, who is also part of Boston Children’s Hospital’s Computational Health Informatics Program (CHIP). “For any condition, some combination of existing drugs may be an effective treatment. Thanks to the increased public availability of high quality data sources, we have the opportunity to ‘compute’ the right drugs at a time scale and cost far below that of drug development.”