Advancing ALS Research with Dr. Rahul Desikan, Dr. Leo Sugrue and their Team in the Laboratory for Precision Neuroimaging

By unveiling the genetic basis of ALS (Lou Gehrig’s Disease), UCSF Radiology faculty Rahul Desikan, MD, PhD, Leo Sugrue, MD, PhD, and their team in the Laboratory for Precision Neuroimaging at UCSF are seeking to improve our understanding of the causes of ALS, stratify individuals based on their genetic risk, and identify new targets for treating this devastating neurodegenerative disease. Learn how you can help donate to their cutting-edge ALS Research.

With complimentary backgrounds in basic and clinical neuroscience and a shared desire to ask (and answer) big questions, when Drs. Desikan and Sugrue met in the Neuroradiology fellowship training program at UCSF they quickly became both friends and research partners. Today as junior faculty in the Department of Radiology and Biomedical Imaging they jointly run the Laboratory for Precision Neuroimaging at UCSF.

“Rahul is a true networker. He just connects with people,” says Dr. Sugrue about Dr. Rahul Desikan, whose ALS diagnosis and story was recently profiled in the Washington Post and Bostonia magazine. “When looking at data, he also looks for and sees novel connections and thinks big. For example, the groups who collected the genetic datasets that he uses in his research were each focused on a particular disease or trait when they collected these data. Rahul’s insight was to combine data from these studies to ask questions about the genes that are shared between diseases. By thinking outside the box he is turning up really novel connections. If we knew the answers ahead of time it wouldn’t be science, but Rahul does seem to have an uncanny intuition!”

At the Laboratory for Precision Neuroimaging at UCSF, the overarching perspective is that brain disorders – from autism to schizophrenia and Alzheimer’s disease – have different underlying causes in different people. The lab’s goal is to develop ways to identify biologically relevant subgroups of patients with a given diagnosis and to use these techniques to stratify patients and better target trials and treatments to their particular illness. Historically, the diagnosis of neurodegenerative disease has been largely symptom based. By drilling down to the root genetic and molecular causes of these disorders the lab hopes to change this, in part by creating genetic ‘risk scores’ for various diseases and by identifying risk genes that are shared between different diseases.

For example, by combing data from genetic studies of 65 different traits and diseases incorporating over 3 million people worldwide the lab is working to identify genes that are shared between ALS and other conditions and to create a genetic ‘risk score’ for ALS. This work has three major potential applications. First, the risk score will allow the researchers to take an individual’s genetic data – the same data used by sites such as 23andMe or ancestry.com – and use it to compute an individual’s risk for developing ALS, allowing the researchers to identify people who might benefit from lifestyle modification or drugs that could delay or prevent the onset of the disease. Second, by stratifying people with ALS into subgroups that share a particular genetic signature the researchers will be able to explore the underlying mechanism of disease in more homogeneous subgroups of patients and ultimately test drugs and other treatments targeted to these mechanisms. Their belief is that drug discovery will benefit from testing drugs on people who share not only the same diagnosis but the same underlying cause. Third, by identifying genes that are shared between ALS and other diseases with known modifiable risk factors ­– such as cardiovascular disease and inflammatory conditions – and studying the role that these risk genes play in ALS-associated neurodegeneration the researchers hope to repurpose existing drugs to prevent or treat neurodegeneration. For example, lowering cholesterol levels or inflammation in people at high risk for ALS whose genetic profile shows strong overlap with cardiovascular or inflammatory disease may prevent or slow the progression of ALS in these individuals.

Aware that their approach is novel and therefore considered high risk from the perspective of traditional funding mechanisms such as the NIH, Drs. Desikan and Sugrue are seeking funding for this project through both traditional and novel crowdsourcing approaches. Learn more about the ALS research project and how to donate to keep this cutting-edge research going.