Gene therapy halts Fatal Brain Disease

By Quirine Eijkenboom

Scientists have long classified gene therapy as a promising treatment for genetic diseases. A reason for this is that gene therapy allows direct replacement of the patient’s mutant gene responsible for the disease with a healthy gene copy. It has nevertheless remained an area of doubt and criticism, as past trials with gene therapy have not always been successful. Now, for the first time, clinicians have successfully used gene therapy to stop the fatal effects of a degenerative brain disease called adrenoleukodystrophy, or ALD. ALD is a genetic, X-linked metabolic disorder that primarily affects young boys (symptoms first start occurring at an average age of 7). It causes nerve cells in the brain to die by destroying myelin, the protective sheath surrounding brain neurons, and thus impedes brain signals from reaching muscles and other parts of the central nervous system.

The above process leads to rapid deterioration of the child’s abilities. The child becomes unable to walk, talk, eat, hear or think and usually dies within five years of diagnosis (http://bit.ly/ALD) . Until now, there were only two possibilities for treatment, bone-marrow transplant providing a suitable donor and transplant with cord blood if saved at birth. However, these transplants are highly dangerous with a mortality rate is as high as 20%. In addition, some patients that do survive are left with lifelong disabilities. (http://bit.ly/GT_ALD)

However, a new study by Eichler, Duncan et.al, published in the New England Journal of Medicine, concludes that gene therapy can halt ALD without any side effects if it is started before the first symptoms are observed in the patient. The study involved 17 affected boys, aged 4 to 13. Each patient received gene therapy administered with a lentiviral vector called Lenti-D. Remarkably, after two years, 15 of the boys functioned normally without any apparent symptoms, suggesting that Lenti-D gene therapy is a safe and effective alternative to stem-cell transplantation in children with early-stage ALD (Eichler, Duncan et.al 2017). More follow-up studies will be necessary to completely evaluate the safety and duration of response of the therapy, however this data already offers great prospects for using gene therapy to combat adrenoleukodystrophy.

The brain and nervous system are often considered to be extremely challenging to treat, but this study presents new hope: gene therapy could be groundbreaking for many patients suffering from neurodegenerative and other genetic diseases, including NGLY1 deficiency. More studies similar to this one will be necessary to establish better expertise with gene therapy, but researchers and clinicians are well on their way.