Rare Disease Day
February 28, 2022 – Imaging Endpoints guides biopharma companies in protocol development and manages the central imaging review for many clinical trials aimed at the diagnosis and treatment of rare diseases. Rare Disease Day, observance on February 28, is designed to raise awareness surrounding the many diseases that affect approximately 200,000 persons in the United States and 300 million worldwide. Every educational effort geared at spreading knowledge about rare diseases, also known as “orphan diseases” is a valuable initiative. Imaging plays a critical role in both the diagnosis and management of rare diseases, from in utero diagnosing to therapy monitoring, and from reliable non-invasive biomarkers to outcome prediction. Because imaging provides exquisite anatomic details and is also capable of sophisticated functional information, it is an excellent tool to include in clinical trials for rare diseases, such as with new therapies for Gaucher’s and Wilson’s diseases.
Gaucher’s Disease, one of the most common inherited metabolic disorders categorized as a Lysosomal Storage Disease (LSD) resulting in the abnormal accumulation of undegraded glucosylceramide in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation; the mechanism remains largely unknown. Because of its ability to assess the visceral and bone marrow manifestations of Gaucher’s, specifically the accumulations of Gaucher cells in the Kupfer cells of the liver leading to hepatomegaly and in the spleen leading to splenomegaly, as well as the bone marrow itself, routine conventional T1- and T2-weighted MR imaging is preferred over CT imaging due to the lack of ionizing radiation. However, despite MR’s ability to qualitatively assess the bone marrow, a clear limitation of MR imaging is its inability to directly measure bone marrow disease, making it less useful for clinicians. This is what led to the adoption of the Dixon’s quantitative chemical shift imaging which leverages the difference in resonance frequencies between water and fat molecules thereby defining the amount of fat (or fat fraction) within the bone marrow. Such imaging methods allow clinicians, researchers and Imaging Endpoints to monitor disease progression as well as the response to various new drug therapies in the context of clinical trials.
Other new quantitative imaging modalities such as Proton density fat fraction and MR spectroscopy have also been introduced to provide a more comprehensive and accurate assessment of bone marrow infiltration, which has proven very useful in monitoring treatment response. Imaging Endpoints has been actively involved in the imaging aspect of therapeutic trials for Gaucher’s disease, which is certainly encouraging for patients suffering from this disease.
Wilson Disease is a rare autosomal recessive inherited disorder of copper metabolism characterized by excessive deposition of copper in cells located primarily in the liver, brain and a few other tissues. Although a wide spectrum of clinical presentations exists, the most significant symptoms of the disease are divided into hepatic, neurologic and psychiatric manifestation. The neurologic presentation develops in almost half the patients and begins by the third decade, with tremor being the most common. Because of its ability to provide anatomical information and biochemical data on the distribution of heavy metal in the brain substance, MR imaging is the imaging modality of choice for diagnostic purposes as it is exquisitely sensitive to the brain findings in the pons, midbrain and basal ganglia, and in correlating clinical severity, duration of disease, and duration of neurologic symptoms with findings on brain MR imaging. Another potential benefit of MR imaging is in monitoring treatment response, which is where Imaging Endpoints has played and is playing an important role in therapeutic clinical trials. Recent advances in imaging science such as radiomics, MR spectroscopy, and functional imaging have improved our ability to correlate phenotypic and volumetric changes on imaging to the treatment response from a specific drug, enabled by the presence of robust and validated scoring systems that have become legitimate surrogate measures of clinical outcomes. It is in such scenarios where large data sets exist that Imaging Endpoints can help to establish and measure meaningful clinical outcomes.
As we observe Rare Disease Day for all patients with rare diseases worldwide, it is important to remember that hope is never far away, and through promising clinical trials that integrate optimal imaging these diseases may ultimately be defeated.
