In 1992, the film Lorenzo’s Oil celebrated the true story of two parents who, despite their lack of scientific training, gathered the know-how and support they needed to develop a treatment for their son, who was suffering from adrenoleukodystrophy, a rare neurological disease.
Nearly 25 years later, Sonia Vallabh and her husband, Eric Minikel, quit their jobs — she as a lawyer, he as a programmer and analyst — and retrained as scientists to find cures for the genetic prion disease that killed Vallabh’s mother and that she herself is at high risk of developing. Soon after, she found herself serving as a patient representative in the White House Precision Medicine Initiative and leading a research initiative at the Broad Institute of MIT.
Today, the notion of the citizen scientist has moved beyond the realm of Hollywood and into the realm of possibility.
Drug development has historically been limited to a select group of medicinal chemists. But with the advent of tools like gene therapy, antisense oligonucleotides, CRISPR gene editing, and RNA modalities, the discovery of new treatments is now within the reach of a broader population of scientists — and even nonscientists. This ability to broaden the base of drug developers has become a critical driver to increase investment in many of the 7,000 rare and ultra-rare disorders for which no treatments currently exist.
To fully realize the potential of this new age of democratization of medical innovation and drug development, I believe that several key trends must be accelerated.
Facilitating customization of genomic R&D tools
Drug discovery is rapidly moving from the analog age to the digital age, to borrow a term from the electronics industry. Advanced sequencing technologies make it possible to interrogate the genetic code to identify the right target, and the growing genomic toolkit gives researchers the power to translate that knowledge into potentially marketable therapies. Stakeholders involved in biopharma innovation can lower the barriers to making drugs by pushing the use of these new technologies out to groups that didn’t have access to them before.
Take CRISPR, for example. While access to this sophisticated technology was originally limited, many academic labs now use CRISPR in their research efforts. And there are now multiple Cas enzymes and CRISPR modalities capable of introducing different types of edits in DNA and RNA, which should expand the universe of diseases amenable to editing.
To ease the deployment of genetic tools to develop precision genomic medicines, I believe it will be essential to broaden and improve the design of translational and personalized preclinical models needed to validate these tools faster and more efficiently. The ability to customize therapeutic development to individual patients based on their genetic makeup is of special importance to democratize the development of genomic medicines for rare and ultra-rare disorders.
Expanding access to next-generation tools
Three decades ago, genomic data could be analyzed only over the course of several weeks by a select number of bioinformaticians. The simplification of data analysis and clinical interpretation enabled by next generation software-driven tools can now quickly identify disease-causing mutations and other genetic abnormalities. Furthermore, technological advances and new tools allow researchers to quickly design and produce nucleic acid payloads like strands of mRNA from an electronic sequence.
Other next-generation formulation tools, like lipid nanoparticles, are being used to carry nucleic acid payloads for gene therapies and vaccines. In the past, developing lipid nanoparticles was a fine art that could be performed only by a handful of specially trained scientists. Now there are desktop machines and libraries of lipids that can essentially reduce what was an extremely complex process of encapsulating nucleic acids in well-formed lipid nanoparticles down to the push of a button. And researchers can make lipid nanoparticles that are modular, so they can take a formulation made for one disease and replace the payload with a therapy for a different disease.
Expanding access to these tools opens the door for any scientist to advance drug discovery.
Decentralizing and custom-scaling manufacturing
The democratization of drug development will also make it possible for patients to be treated at the right time and place. Current advances in biomanufacturing are making the production of custom genomic medicines a reality, allowing the creation of regional centers that can scale up, down, and out genomic medicines manufacturing, for patient populations ranging in size from one to thousands.
Take, for example, manufacturing CAR-T cell therapies. Making these treatments, which begin with a patient’s own immune cells, is a cumbersome process that involves multiple steps in potentially different locations and often multiple visits to a doctor’s office. With smaller, more efficient equipment and more flexible design of manufacturing plants, the biopharma industry could decentralize CAR-T production and make the process more accessible, consistent, and patient-friendly. The ideal scenario would ultimately be CAR-T production at the bedside, with single devices that could extract cells from the patient and process and modify them with the desired genetic alteration to create viable and potent cancer-fighting CAR-T cells that are administered back to the patient.
The same concept should apply to a wide range of therapeutic modalities. For example, gene therapies based on viral vectors could benefit many patients with genetic diseases. Similarly, therapies based on antisense oligonucleotides could be developed to treat ultra-rare diseases caused by genetic mutations that occur in a handful of patients — or maybe even in just one. Private and public groups such as the n=1 Collaborative and the nonprofit n-lorem Foundation are working toward creating paths to enable the democratization of these potentially life-saving treatment options, and multiple organizations are spearheading efforts to develop appropriate regulatory and reimbursement paths to make this possible.
Evolve the life cycle of drug development: federation and collaboration
To fully realize the promise of democratized drug development, the biopharma industry needs to move from a vertical model, in which researchers work in silos contained within companies or academic institutions, to a federated model that allows disparate entities to pool data gathered in the discovery process. That means consolidating the know-how, and potentially sharing the costs and risk among multiple stakeholders, including academic scientific innovators, clinical research organizations, drug developers, and public entities.
This risk sharing and diversification in partnerships could maximize patient outcomes, increasing the likelihood of success for all partners involved. And it will ensure that finding cures for previously unsolvable diseases will be well within the reach of many more people than it has ever been in the past.
Vanessa Almendro is a vice president and head of innovation at Danaher Corporation, a global science and technology innovator. Several Danaher companies support genomic medicine discovery, development, and next-generation biomanufacturing.
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