From rare conditions like COL4A1 to hearing loss and inherited dementia, gene therapies can save lives and rewrite futures.

Robbie, 9, and his family

Gene therapy is a promising treatment option for more than 7,000 rare diseases that currently have no cure. 

Many diseases, such as motor neurone disease, spinal muscular atrophy and haemophilia are caused by faults in our genes. These faults cannot be corrected by traditional medical treatments. 

Gene therapies work by creating synthetic genes that can “correct” or “silence” the faulty genes that are causing a patient’s disease. To deliver the new synthetic genes into a patient’s target cells, we use adeno-associated viruses that act as a vehicle to transport the new genes to where they need to be in the body.

Clinical trials have shown that gene therapies have the potential to halt disease progression, and improve symptoms. Human trials have also reported remarkable safety and efficacy data. 

A turning point for motor neurone disease

Lumbar Puncture - treatment for MND
NIHR Sheffield Biomedical Research Centre

The Food and Drug Administration (FDA) has authorised the first approved drug for a rare form of motor neurone disease (MND) based on the results of a Phase 3 clinical trial completed at the University of Sheffield. 108 MND patients known to have the faulty SOD1 gene took part in the pioneering Phase 3 clinical trial funded by biotechnology company Biogen Inc. 

Results of the trial show that the treatment successfully hits the therapeutic target, and might reduce the loss of motor neurons and allow the regeneration of connections between muscles in the body. The trial showed significant improvements in patients’ symptoms, with one patient in a wheelchair later able to walk without sticks.

“I have conducted more than 25 MND clinical trials and this trial is the first trial in which patients have reported an improvement in their motor function. Patients with SOD1 mutations are relatively rare, but this trial is going to change the future of MND trials for patients. Not only can we look at other genes which also cause MND, but we now have a biomarker which we can measure to see if a treatment is working. This is going to make trials much more efficient. In future we may be able to tell in three to six months if an experimental therapy is having a positive effect.” Professor Dame Pamela Shaw, Director of the Sheffield Institute for Translational Neuroscience and the National Institute for Health Research Sheffield Biomedical Research Centre.

Read more about this breakthrough

Life saving treatment of spinal muscular atrophy

Baby Sebastian smiles at the camera in the foreground with his mum, Dharmisha, in the background
Sebastian and Dharmisha

Spinal muscular atrophy (SMA) is a devastating disease which affects children. It is caused by an abnormal survival motor neuron (SMN) gene, which leads to a reduction of SMN protein levels. Approximately 50 per cent of affected children die before two years of age. 

Researchers at Sheffield demonstrated restoration of the missing SMN protein using gene therapy replacement. This pioneering preclinical work provided the confidence for pharma companies to invest in human gene therapy trials which led to FDA approval of Zolgensma®. A single dose of Zolgensma®, which delivers a viral vector called AAV9, encodes the missing SMN protein, resulting in babies with type 1 SMA achieving milestones, where they previously would have declined.

“Before Zolgensma® we were going to baby groups but Sebastian wasn’t really able to participate fully. He wasn’t really able to play. Now Seb is a little mover! He can sit unassisted, he can roll left and right fully, he has even stood independently briefly.

Zolgensma® changed our lives. Seb will never know any difference to how his life pans out. But for my husband and I, it saved his life and more. It’s giving him mobility that he had lost. And the possibilities are unknown but exciting. But knowing that Seb will not deteriorate and regress is such peace in our hearts and minds. It’s monumental.” Dharmisha, mum to Sebastian who received a treatment of Zolgensma® for his SMA in 2021.

Read more about our progress with SMA

Read more about baby Markuss