Innovative research efforts such as the Precision Medicine Program at the ALS Therapy Development Institute are well positioned to help advance the translation of basic research findings such as this one regarding NEK1.
Recently, a paper about NEK1, a new candidate gene related to ALS was published in Nature Genetics . This paper outlines a massive experiment conducted by collaborators in many different institutions through a program called Project MinE.
In short, the collaborators looked at data produced from samples provided by 18,926 individuals, approximately 62% of which were those without a known family history or current diagnosis of ALS (i.e. controls). These samples came from 11 different countries. They were processed through an experiment called whole exome sequencing, which is the process by which researchers sequence only the genes currently known to encode for proteins, or about 1% of the human genome. This is slightly different from whole genome sequencing, which is the experiment that sequences all the genes of the known human genome (The whole genome is sequenced in the Precision Medicine Program at the ALS Therapy Development Institute).
The NEK1 finding does add useful information to what we know about the genetics related to ALS. However, it is important to note that there are dozens of candidate genes now known to be associated with people with ALS, including SOD1 found more than 25 years ago for which an effective treatment has yet to be developed. While finding out new genes associated with ALS is a very important basic research discovery and adds important new information to the fight, this paper doesn’t speak about a specific therapeutic for NEK1-mediated ALS. It is important to recognize the value of this finding, but also important to recognize the significant amount of additional work which now ought to take place to translate this basic research finding into preclinical modeling and screening tools and eventually into therapeutics for ALS. That work will take significant investment of both time and funds.
Many next steps could be pursued for NEK1, and the authors of the paper allude to their importance. These include the development of preclinical models, such as cells and animals, in which the mutant NEK1 variants identified are expressed. These models will allow for researchers to understand more specifically the potential role that NEK1 may play in the onset or progression of motor neuron disease or ALS.The creation and characterization of these models are an important next step.
Innovative research efforts such as the Precision Medicine Program at the ALS Therapy Development Institute are well positioned to help advance the translation of basic research findings such as this one regarding NEK1. For example, the PMP database at the Institute can be used to identify carriers of these mutant genes, the characterization of their disease phenotype and identification of mutant gene expression related targets using isogenic and human derived iPSc lines against which specifically targeted treatments could be screened.
We believe that combining data together – a person’s background data, their genetics and cellular and other models to study and screen drugs – is a valuable asset for the ALS research community to access in order to advance treatments. It is so important that the PMP program at the ALS Therapy Development Institute be fully funded so that its true power to help identify subtypes of ALS and screen potential treatments for each is fully realized sooner rather than later.
The ALS Therapy Development Institute is currently seeking to enroll upwards of 450 additional people with ALS in the PMP and encourage anyone with ALS to apply online at www.als.net/pmp2. Crucial and immediate funding is needed to continue the momentum we have with PMP.To invest in applying the latest precision medicine techniques to ALS, donate now at www.als.net/pmp2.
Precision Medicine Program
Nature Genetics Publication
Project MinE Website