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Rare Diseases Q3 2020

No treatment for rare genetic diseases? Nonsense!

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Dr M. Adam Ali

Adam Ali is a Health Education England fellow in Medical Education at MedShr, the world’s leading discussion platform for doctors. He also holds honorary posts as an Honorary Research Assistant at UCL Institute of Ophthalmology: Ocular Biology and Therapeutics, and an Honorary Research Fellow at Moorfields Eye Hospital.

Exciting new treatment options are emerging for “nonsense-mediated” rare diseases: genetic conditions in which a small mutation in the genetic code prevents the production of normally functioning proteins.

Although individual diseases and conditions can be exceedingly rare, rare diseases as a whole constitute a significant burden of morbidity in the general population. For example, childhood blindness and visual impairment affects approximately 1.4 million children worldwide and approximately 1 in 2500 children in the UK, and it is thought that about one third of these cases is likely caused by genetic disease. 

Better treatment options for rare diseases

Grouping rare diseases by the mechanism by which they arise can lead to better treatment options, as seen in treatment of “nonsense-mediated” rare diseases, where an abnormal early ‘stop’ signal can affect normal protein production and cause blindness. Over the past decade, a myriad of new approaches to treating such diseases have been developed. These have included the so-called ‘bionic eye’, pharmacological approaches using drug treatments, and surgical delivery of viral vectors.

Drug treatments for nonsense diseases

An exciting area of development is the use of ‘readthrough’ drugs to treat nonsense-mediated genetic diseases causing blindness. It was recently discovered that gentamicin, a well-known and commonly used aminoglycoside antibiotic, has ‘readthrough’ properties. This means that in nonsense genetic diseases, the use of such medicines will help cellular machinery to ‘read through’ the gene – in other words, ignore the abnormal stop signal – and make a fully functional protein.

Another group of medicines are those designed to protect cells against nonsense mutations. Known as nonsense-mediated decay inhibitors, these drugs are showing promise in treatment of conditions ranging from ocular genetic diseases to Duchenne Muscular Dystrophy (DMD), cystic fibrosis (CF) and certain types of lung cancer.

Viral vectors

Patients with Leber congenital amaurosis type 2 develop a retinal dystrophy caused by mutations in the RPE65 gene. Luxturna, the first gene therapy product approved by the FDA for a retinal disease, allows an AAV2-RPE65 vector to help compensate for the loss of protein caused by these mutations. These patients showed a clinically significant improvement in their vision in dimly lit conditions, with improvements persisting up to 3 years after surgery. Viral vectors are still a subject of much research, and these successes have led to clinical trials in Stargardt disease and Usher syndrome.

Retinal implants and the Bionic Eye

Retinal implants, prostheses and the so-called ‘Bionic Eye’ provide non-viral approaches to restore vision in blinding conditions. These have been used in common conditions including macular degeneration, but also in rare genetic conditions like retinitis pigmentosa. Recent developments have reported ocular prostheses which are excitingly similar to the human eye. For example, this eye has a wide field of view of 100°, compared to 130° in the human eye, and the nanowire in the artificial retina detects an average of 86 photons per second in low light intensities, comparable with human retinal photoreceptor cells. Moreover, the curved shape of the prosthesis means nanowire density can be packed into even higher density than that of photoreceptors in the human retina.

Such developments provide multiple new treatment options to patients where treatment options have traditionally been limited.

Doctors and other healthcare providers are encouraged to join the Rare Diseases Discussion Group on MedShr to discuss diagnosis and treatment of rare diseases with peers from around the world.

MedShr is the world’s leading case discussion platform, enabling clinicians to securely share and discuss clinical images and cases within a global professional network. MedShr is growing rapidly with over one million members in 190 countries using the platform to learn from each other and to work together to provide better care for their patients. Sign up for free at

1. Bordet T, Behar-Cohen F. Ocular gene therapies in clinical practice: viral vectors and nonviral alternatives. Drug Discov Today. 2019;24(8):1685-1693. doi:10.1016/j.drudis.2019.05.038
2. Christopher M Way , Dulce Lima Cunha & Mariya Moosajee (2020). Translational readthrough inducing drugs for the treatment of inherited retinal dystrophies, Expert Review of Ophthalmology, 15:3, 169-182, DOI: 10.1080/17469899.2020.1762489
3. Jiang H. Artificial eye boosted by hemispherical retina. Nature. 2020;581(7808):264-265. doi:10.1038/d41586-020-01420-7

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