Natural History Studies Vital to Finding Treatments for Rare Diseases

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The lack of information on rare diseases can create difficulty in developing drugs to treat them. To help, it is important to study the natural history of rare diseases.

Compared with common diseases, researchers know little about rare disease signs and symptoms, how the disease changes over time, and ways in which the disease affects the lives of patients and their families.

Natural History studies track the course of a patient’s disease over time. They identify demographic, genetic, environmental, and other variables that shape the drug development process

Dr. Eric Pierce, Massachusetts Eye and Ear

“In general, Natural History studies can be helpful precursors to clinical trials of potential treatments for inherited retinal degenerations for multiple reasons,” said Eric A. Pierce, MD, Ph.D., with Massachusetts Eye and Ear. “For example, they can help identify the tests or measurements which would be most appropriate to use as endpoints in therapeutic studies.”

Another way to view such studies is to “Begin with the end in mind,” as suggested by Anne R. Pariser, MD, in her work on Natural History studies for the U.S. Food and Drug Administration

Natural History data provide knowledge and an independent understanding of a disease, while establishing an essential foundation for building drug development programs. These studies have been characterized as the “pillar of epidemiologic research on rare conditions,” and, along with assisting in developing drugs, they help with patient care, best practices, research priorities, and clinical trial readiness, according to Dr. Pariser, director of the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences.

The studies give scientists and researchers a better estimate of the prevalence of the disease, help identify potential biomarkers, affect clinical outcome assessments, and determine the feasibility of established assessments for clinical trials.

A rare disease is a disease or a condition that affects fewer than 200,000 Americans. With a relatively small number of people affected by the 7,000 diseases considered rare, scientists sometimes face daunting odds in finding enough people meeting study requirements.

In the Leber congenital amaurosis (LCA) community, scientists are looking for people to take part in different stages of drug development.

Editas Medicine, a genome-editing company based in Cambridge, Mass., is sponsoring a Natural History study of LCA10, known by its gene name CEP290, to inform the design of potential future treatment studies involving genome editing in LCA10. The purpose of the study is to understand and better describe the clinical course of LCA10-related retinal degeneration that is associated with a particular genetic change in the CEP290 gene called c.2991+1655A<G.

The study will be used to characterize the range of visual function in patients, evaluate which visual tests may be most useful, and determine the rate of change in visual function over a one-year period.

Dr. Pierce, director of the Ocular Genomics Institute and the William F. Chatlos Professor of Ophthalmology at Massachusetts Eye and Ear (MEE) and Harvard Medical School, is the principal investigator at one of the seven sites in the United States and Europe actively recruiting patients for this Natural History study. For more information, call MEE at 617-573-6060 or visit Study details also can be found at Identifier: NCT03396042.

The two groups of conditions below describe the parameters for taking part in the study. Taken together, they illustrate the potential difficulty in finding the 40 participants needed for the study of this rare disease.

Patients must meet six conditions, known as inclusion criteria:

  • 3 years of age or older;
  • Abnormally decreased vision, with examination and test results consistent with inherited retinal degeneration due to mutations in the CEP290 gene;
  • Able to cooperate with assessments relative to the patient’s age;
  • Clear ocular media and adequate pupil dilation in at least one eye to permit good-quality examination of the interior surface of the eye opposite the lens and optical coherence tomography (OCT) imaging;
  • Able to successfully navigate a mobility maze at a level of difficulty below the maximum performance level.

Patients cannot participant if one or more of the five following conditions, called exclusion criteria, exist:

  • Visual acuity of no light perception in both eyes;
  • History or current evidence of a range of medical conditions that may preclude attending scheduled study visits, safe participation in the study, or affect the study results;
  • History or current evidence of ocular disease in either eye that may confound assessment of this inherited retinal disease;
  • Currently receiving gene therapy and/or has received gene therapy;
  • Currently enrolled in an investigational or interventional drug or device study and /or has participated in such a study within 30 days of screening.

If you or your loved one is interested in taking part in a Natural History study, please register with the, a free, secure, online registry managed by the Foundation Fighting Blindness for patients who have been diagnosed with an inherited retinal disease (IRD).

Participants currently are being recruited for a Foundation-funded Natural History study of disease progression in patients with USH2A-related retinal degeneration associated with congenital hearing loss (Usher syndrome type2a) or non-syndromic retinitis pigmentosa (RP39).

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