Rare diseases are defined as chronic diseases that affect only 0.05% of the population or fewer. There are over 7000 known rare diseases, and taken together, they affect around 8% of the world’s population. In California, that means over 3 million patients have a rare disease. Worldwide, the prevalence is over 500 million patients. The vast majority of these diseases have no treatments. Most doctors are unaware of these diseases and many patients go years without a diagnosis. Most rare diseases have a genetic basis, but genetic testing remains largely inaccessible to most Californians. Moreover, most general physicians and even specialists are not adequately trained to interpret genomic testing. There is a tremendous, untapped opportunity to advance the diagnosis and treatment of patients with rare diseases in California.
UCLA has thus launched in 2019 a California Center for Rare Diseases at UCLA, which will transform the lives of patients with rare diseases by discovering the genetic causes of their diseases; caring for them compassionately through innovative treatments; offering clinical trials and other treatments aimed at ameliorating or curing their disorder; and offering education and advocacy. We enhance the mission of the Institute for Precision Health (IPH) at UCLA by deepening our understanding of genetic and epigenetic factors that lead to rare diseases. We will offer personalized medical care for each patient (children and adults) based on genetic and research tests, including repurposing drugs for individual use and running clinical trials. We will make long-lasting, transformative changes in the field of rare diseases by bringing together researchers from around UCLA and across the world to our cause.
The Center for Duchenne Muscular Dystrophy is the first of its kind in the west and a cornerstone of the California Center for Rare Diseases at UCLA. The center’s efforts span education and outreach, leading-edge research, drug discovery, clinical trials and care.
The California Center for Rare Diseases at UCLA will offer advanced diagnostics and treatments for patients with rare diseases. To improve diagnoses, the Center will operate clinics in collaboration with UCLA Health for the evaluation and treatment of pediatric and adult patients referred for these diseases. The clinic will operate a procedure room to facilitate obtaining timely samples (e.g., muscle biopsies) for immediate transport to UCLA-based research labs. Genetic testing will offered through the UCLA Clinical Exome Service or through other partner services. Exome, genome, and transcriptome sequencing are all central to our workup of rare diseases.
Many tests needed for making a specific, genetic diagnosis are not available in the hospital’s clinical lab or in CLIA labs around the country. To complete the diagnostic workup, we will offer in-house research tests for rapid phenotyping and functional assessments, including novel assays not yet available in routine clinical laboratories. When genetic variants are identified that could explain the patient’s disease, we will validate those variants for their pathogenicity. We will establish methods for validating variants in novel genes. These services will primarily be for the Center’s clinic, but ultimately will also be offered to the worldwide community to rare disease specialists on a scheduled, one-off basis.
Laboratory-based services of the Center will include participating with efforts of the IPH for population-scale studies. The Center will offer or will work with UCLA core labs to offer specific services such as iPSC preparation from PBMC or fibroblasts, establishment of EBV-immortalized B cells, and specialized culture of various cell types. The Center will help maintain IRB-approved protocols to obtain and analyze blood, tissues, muscle, bone marrow, and genetic data of patients and families with rare diseases.
A major goal of the Center is to offer treatment to patients with rare diseases. These treatments include existing drugs that can be repurposed; new antibodies and immune therapies; DNA and RNA-based drugs that alter the transcription of pathogenic genes; plus future cellular, stem cell, and gene therapies.
Our clinic will offer advanced treatments for single patients in a personalized fashion. These treatments are the ultimate in Precision Health, guided by genetics and other biochemical testing. Treatments can include, for example, the use of monoclonal antibodies or other biologicals for genetic immune disease patients; use of novel exon-skipping drugs in Duchenne muscular dystrophy; and so on. For suitable new drugs that meet the needs of are diseases, the Center will run investigator-initiated clinical trials. These may include, for example, new biologicals or inhibitors. A link to all the current clinical trials is here.
As cellular, stem cell, and gene therapies become available, the Center will coordinate and execute the relevant clinical trials. To facilitate these clinical trials, we will hire a coordinator who will work in collaboration with the divisional clinical trial offices.
To move the field forward worldwide, we are committed to publishing our findings in Rare Diseases rapidly, including methods for validating putative variants, case reports, treatment protocols, outcomes of clinical trials, and so on.
Volumes of data are collected for each patient with rare diseases. The Center for Rare Diseases will work with IPH and UCLA Health to manage these research data in a secure but sharable fashion.
The Center for Rare Diseases will offer opportunities for clinical fellows and faculty from divisions across UCLA to participate in the Rare Diseases clinics and meetings to raise education and awareness of rare diseases, thereby accelerating the process of making definitive diagnoses and obtaining appropriate therapy. We will provide lectures to the residents and fellows (internal medicine and pediatrics) to further increase awareness and expedite referrals. Please contact us to schedule a talk.
To educate the UCLA community about rare diseases, The Center will run a seminar series that will bring junior rising stars and senior leaders to campus for 1-2 day visits. The visits with local faculty, lunch with students and postdocs, and dinner with faculty will be modeled after other seminar series. The visit will culminate in a seminar. A schedule of seminars is forthcoming.
To advocate in the community for Rare Disease patients, The Center will champion various advocacy groups that service Los Angeles and California, broadly. The Center will host tables and booths, sponsor educational seminars for patients and activities to encourage patients to meet and help each other, encourage near-campus gatherings of patients and families with fellows and faculty, Q&A days, barbeques, and sporting events. Specifically, the Center will support administratively the mass mailings to patients, families, and other stakeholders that are needed for events.
If your group wants us to present at your event, please contact us.
The Center will seed the efforts of the various groups at UCLA interested in developing research projects and tools around rare diseases. The Center will launch a Pilot Project Program in 2019. We will have a rolling submission process that emphasizes the collaboration between faculty across the UCLA community. Deliverables will emphasize utility to the Center plus an explanation about how the project will develop into an NIH-fundable effort or a core-managed capability. A publication should result from each awarded project. Awardees will be required to give a presentation at a yearly seminar. Ideally, the three-year goal of the Pilot Project Program is to engender at least one funded R01 grant and at least one non-NIH-funded grant (e.g., from a foundation).
Watch this space for more details in 2019.
The Center will store primary specimens of muscle, peripheral blood mononuclear cells (PBMC), and other tissues. Our IRB protocols allow for indefinite storage of cells, tissues, and genetic material. Barcoding and storage of specimens internally will be performed through an on-campus collaboration with Pathology or with a collaborator/vendor approved for this kind of research.
“Precision health requires collaboration across many disciplines, from basic science and genetics, to engineering and clinical medicine. Like no other, the UCLA Institute for Precision Health serves as a hub to bring all these disciplines together.”
—Kelsey C. Martin, MD, PhD
Dean, David Geffen School of Medicine at UCLA