At the Sean M. Healey & AMG Center for ALS, compassionate clinical care converges with cutting-edge research every day. The laboratories at the Charlestown Navy Yard are humming with investigators researching the latest breakthroughs in ALS and bringing us closer to a cure.

One of the investigators is Ghazaleh Sadri-Vakili, M.S. Ph.D., who runs the Neuroepigenetics Lab at the MassGeneral Institute for Neurodegenerative Disease. Dr. Sadri-Vakili and her team focus on identifying common mechanisms that cause neurodegenerative disease to identify novel therapeutic targets. The laboratory has identified disease specific alterations in multiple cellular pathways using human samples as well as cellular and animal models of ALS and other diseases. Dr. Sadri-Vakili’s lab is currently assessing the pathogenic role of neuroinflammation, oxidative stress, and the epigenome in ALS.

Dr. Sadri-Vakili’s latest work explores the impact of gene fusions on ALS disease progression. The following information was shared by Dr. Sadri-Vakili:

Genetics is an important risk factor for ALS and over 50 causative or disease-modifying genes have been identified and linked to the disease. Additionally, genetic risk factors also contribute to sporadic ALS; however, the causes of more than 80% of cases are still unknown. One potential genetic cause of ALS may be structural variants, such as deletions, inversions and translocations within the genome that may lead to the formation of gene fusions- when two independent genes are juxtaposed to form a new gene. We recently used publicly available RNA-Seq datasets from Target ALS and the ALS Consortium and deployed an open-access software to identify any possible gene fusion events in ALS.

 Our analysis revealed that there is a significant increase in fusion genes in ALS and identified 90 rare gene fusion pairs in ALS, defined as those absent from control cases as well as from known cancer databases, given that fusion events are well-characterized in cancer. Since the causes of more than 80% of ALS is unknown, the identification of ALS-specific gene fusions may improve our understanding of the mechanisms underlying motor neuron loss and identify novel potential therapeutic targets. Our results were published in Muscle and Nerve Journal earlier this month.

 Additionally, there is an urgent and unmet need for biomarkers for both ALS diagnosis and prognosis. In this respect, ALS-specific gene fusions may be a viable diagnostic biomarker and, once we characterize their molecular consequences, they may also serve as potential prognostic biomarkers. Our team was recently awarded with a grant from ALS Finding a Cure to assess whether gene fusions are viable biomarkers for ALS.

 In summary, we predict that ALS-specific gene fusions may improve many aspects of clinical care as already demonstrated in the field of oncology and are now working to understand how gene fusions contribute to ALS.