When we injured ourselves , our body’s mechanisms turns damaged muscle into bone. It is not a science fiction rather than an unusual genetic disorder known as fibrodysplasia ossificans progressiva (FOP) that locks people in a second skeleton as they age.
A finding in the article of the journal Nature Genetics refer to a conspicuous genetic association between FOP and a metastatic childhood brain tumor, and this discovery may offer novel approaches to treat children with the incurable disease.
A famous case is that Harry Eastlack in five year old broke his leg. During his recovery , Harry’s knee and hip became hardened as bone start to form on his thigh muscles. As he grew up this condition spread around his body, freezing up his muscles. Exposure of the rare disease from the perspective of genes may benefit children with a brain tumor called diffuse intrinsic pontine glioma(DIPG). When Dr Chris Jones attempted to find the driving gene faults of DIPG, more striking was the discovery that the same few spelling mistakes matched those responsible for FOP.
A surprising genetic crossover as clues for treatments
The identified gene is known as ACVR1 encoding a key protein ALk2. A child carrying the faulty gene in all cells at birth would predispose to develop FOP. Also, if the faulty gene is present only in the precursor cells of the specialised glials then child could suffer from DIPG.
The variant of ACVR1 produces a hyperactive form of ALK2 that permanently switches on a set of signals in cells. The precise role these signals play in DIPG is not yet known, but thanks to research into FOP there are potential drugs already being developed that target the faults in ACVR1. These are hoped to be repurposed as a new treatment for children with DIPG in the future.
A selection of DIPG cells with the faulty ACVR1 gene in the lab were treated with one of these promising compounds, and the result showed that it was effective at killing the cells. However, It’s big challenge to turn these compound suitable for treating DIPG patients.
This study is a fascinating example of how two drastically different, but equally devastating, diseases can be brought together by the genetic events.
Reference : Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nature Genetics 2014, DOI: 10.1038/ng.2925