Rare diseases are individually rare but collectively common. Rare diseases are often devastating in babies, but with early diagnosis could potentially be treated. The population is increasing and therefore there is an increased need for newborn screening and improved treatment.
The UK rare diseases framework aims to help patients get a final diagnosis faster, increase awareness of rare diseases among healthcare professionals, better the coordination of care and provide improved access to specialist care, treatments and drugs. The themes in the UK rare diseases framework include the patient voice, pioneering research, digital data and technology, collaboration and wider policy agreement.
With the increasing number of patients being diagnosed there is a clinical need for awareness, access to genetic testing and cascade screening to increase survival. This emphasises the importance of rare diseases as powerful drivers of research and therapeutics.
Lysosomal storage disorders (LSDs) are a group of rare genetic disorders that are characterised by the accumulation of substances in cells due defects in lysosomal function. Gaucher's diseases is an LSD that is characterised by the deficiency of the glucocerebrosidase enzyme and leads to skeletal disfigurement. Fabry disease is an LSD that is characterised by the deficiency of the alpha-galactosidase enzyme and causes the abnormal storage of lipids. Neimann Pick disease causes the enlargement of the spleen and or the liver. MPS affects the bone, cartilage, corneas, skin and connective tissue. MLD affects the central nervous system. Mannosidosis is caused by alpha-mannosidase enzyme deficiency. Pompe disease is characterised by the abnormal storage of glycogen.
The current treatments for LSDs include bone marrow transplantation, enzyme replacement therapy, substrate reduction therapies and gene therapies. The efficacy of treatment is limited by the target organ/tissue, central nervous system involvement, the natural history of disease, biomarkers/monitoring and anti-drug antibodies.
To assess new treatments for lysosomal storage disorders there are some problems. The first problem is that LSDs are progressive and lifelong conditions this means that they are associated with a large burden to the patient and large costs for treatments. The second problem is that clinical phenotypes of LSDs are widely variable and are often not captured well by clinical trials. The third problem is that there is a lack of specific and sensitive biomarkers to risk-stratify and assess response to treatment. The fourth problem is that the safety greatly outweighs the efficacy in clinical trials, this creates a lack of clinically meaningful endpoints.
Sources
https://www.cuh.nhs.uk/our-services/lysosomal-disorders-service/ Assessed and Endorsed by the MedReport Medical Review Board