Canadian company QLT has completed enrolment in its natural history study for inherited retinal diseases caused by mutations in the RPE65 and LRAT genes. This includes some forms of retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). The aim of the retrospective study is to gather data on the natural progression of the diseases in people over time, including from childhood through to adulthood.
The study included both participants who had previously received treatment in QLT-sponsored clinical trials with QLT’s synthetic oral retinoid product, QLT091001, as well as participants who had not received any prior therapeutic treatment. The intention of this study was to better observe and understand the long term natural disease progression of untreated patients, and to provide comparative data to further assess the extent to which treatment with QLT091001 may prolong or improve visual function relative to the underlying natural disease progression. The company expect the study to provide important data to support the on-going development programme for its potential therapy QLT091001. In total, 59 participants across 10 clinical study sites in Europe, the U.S. and Canada were enrolled in the study, 25 of whom had participated in previous clinical studies with QLT091001, and 34 of whom had received no previous treatment. Results from this study are expected in the near future.
Natural history studies collect information from a population over time to track the course of a disease and to better understand how disease develops, as well as when and how best to treat it. Natural history studies are an important source of information for scientists, clinicians and people affected by the condition. This type of study is particularly significant in rare diseases, which are often not well documented and poorly understood due to low numbers of people affected and the complexity of some conditions.
In order to develop a therapy to treat a disease, scientists must first understand the cause and progression of the condition. Well-conducted natural history studies provide valuable information that can inform medicines research and development. This type of information can be used in a number of ways including;
Natural history studies also enable people affected to better understand their condition and what to expect as the disease progresses. This is important so that people can prepare and plan for the future.
In addition to the QLT study above, natural history studies have been carried out for a number of inherited retinal degenerations including Stargardt disease, Usher syndrome, retinitis pigmentosa, diabetic retinopathy, age-related macular degeneration (AMD), dry eye and X-linked retinoschisis. Details of some of these studies are provided below.
This study, coordinated by Foundation Fighting Blindness Clinical Research Institute, began in October 2013 and is still on-going. However, it is not currently recruiting participants. The primary objective of this natural history study is to assess the yearly rate of progression of Stargart disease using information obtained from the 365 individuals that have been enrolled across 12 sites in the US and Europe. Participants included in this study range from six years and older and attend regular six month follow up visits for up to 24 months. It is estimated that this study will be completed by 2017. Click here for further information.
The majority of people who have Stargardt disease have the recessive form of disease, involving mutations in the ABCA4 gene. This project is a prospective natural history study led by the National Eye Institute and is currently recruiting participants in the US. The primary outcome for this study is the establishment of a detailed registry of patients with ABCA4-related retinopathies in anticipation of future clinical trials. Another goal is to identify best outcome measures to use in a clinical trial. To date, an estimated 70 participants have been enrolled from 12 years of age or older. It is not yet known when this study is to reach completion. Click here for more information.
The Natural History of the Progression of Atrophy Secondary to Stargardt Disease Type 4: PROM1-Related Macular Dystrophy (ProgStar-4)
A very rare form of Stargardt disease called Stargardt type 4 is caused by a mutation in the prominin-1 gene (PROM1) gene. This study is a prospective natural history study being led by John Hopkins University in the US. Very little clinical data exists to date about this condition. The ProgStar-4 is an important opportunity to investigate the progression of this disease and help establish patient cohorts worldwide for future clinical trials. To date, 15 individuals have enrolled and recruitment to the study continues in the US, Germany, Switzerland and the UK. The study is expected to reach completion in March 2018. Click here for further details.
This is a prospective natural history study led by the National Eye Institute in the US. The study will explore the clinical and genetic aspects of Usher syndrome. The study commenced in 2005 and is currently on-going but not recruiting participants. In total, 237 individuals have been enrolled and include participants affected with all three clinical types of Usher syndrome. Unaffected family members, primary parents and siblings were also enrolled to assist in providing crucial information for linkage analysis. Click here for more information.
This retrospective natural history case series was led by Moorfields Eye Hosptial, NHS Foundation Trust and Foundation Fighting Blindness. The purpose of this study was to evaluate the phenotypic variability and natural history of ocular disease in a cohort of 28 individuals with MYO7A-related disease. Mutations in the MYO7A gene are the most common causes of Usher syndrome, type 1. Twenty-eight participants from 26 families participated. Conclusions from this study were published in the Ophthalmology Journal in February 2014. It was concluded that MY07A-related ocular disease is variable. One observation was that central vision typically remains preserved at least until the third decade of life, with 50% of affected individuals reaching legal blindness by 40 years of age. Click here for more information.
This was a prospective natural history study led by Applied Genetic Technologies Corp (AGTC) in the US. The objective of the study was to evaluate participants with XLRS in a clinical setting and gather data on disease progression. In 2015, AGTC announced data evaluating the natural history of individuals with X-linked retinoschisis at the 48th Annual Retinal Society Meeting. The data from this study will enhance the understanding of the natural history of this rare disease and will facilitate better design of future clinical trials.
CRIBBS is an observational 10-year prospective study investigating the natural history of Bardet-Biedl syndrome (BBS). The aim of the study, conducted by the Marshfield Clinic Research Foundation, is to gather comprehensive health information from individuals diagnosed with BBS in a single repository. This information will be used to inform patients, families, and physicians about the complex features of BBS and will serve as a platform for researchers to develop effective and targeted treatment strategies for patients with BBS. The estimated enrolment for the study is 500 participants with a planned completion date of December 2025. Click here for more information.
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