Curing genetic diseases

One of the most difficult things that we have to deal with, as neonatologists and pediatricians, is to announce the diagnosis of a lethal, or a lifelong life-changing, genetic diagnosis. Spinal Muscular Atrophy (Werdnig-Hoffman disease), and Haemophilia A are 2 such diseases. These are examples of the kind of disease that would be great if we could correct the abnormal gene, a dream that has been around since we discovered the genetic basis of those disorders.

Well now it appears that this might soon be truly possible. After several mis-steps, and unsuccessful attempts at gene therapy in the past, 2 recent issues of the New England Journal of Medicine have announced successful apparent partial genetic correction. Mendell JR, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. New England Journal of Medicine. 2017;377(18):1713-22. In this study there were 2 dose schedules, the low dose schedule was tolerated, but not very effective, the high dose schedule led to achievement of motor milestones that are not normally achieved by infants with this disorder. By 18 months of age most babies with type 1 SMA are normally either dead or permanently ventilated, in this group none of them were. It seems like the treatment was still effective out to 2 years after the single infusion.

The other remarkable advance is gene therapy for hemophilia A. Nine severely affected men had a single intravenous infusion of gene therapy, and 6 of the 7 who had the high dose had complete normalization of their factor 8 levels, the 7th had increased levels up to mild hemophilia concentrations. Up to a year after the treatment factor 8 levels remained good, and there was a marked clinical improvement.

Further follow-up will be required to be sure that these interventions are safe, both used adenovirus vectors to deliver the genetic therapy, but in both studies there were only transient mild hepatic effects of the viral vector.

One day delivering the distressing diagnosis of SMA type 1, or hemophilia A will become an opportunity for cure rather than the death-sentence, or life-sentence, that they now are. Let’s hope that the availability and price will be such that all eligible babies will be able to receive therapy.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
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