Rahul Kumar has a burning curiosity to uncover the biological mechanisms driving neurodegenerative diseases. After finishing his combined Bachelor of Science/Master of Science degrees at a prestigious research institute in India, he moved to Canada so he could work on ALS research. He joined Dr. Peter McPherson’s lab at the Montreal Neurological Institute and Hospital (The Neuro) at McGill University in 2017.

Kumar was recently awarded a $75,000 Trainee Award from the ALS Canada Research Program to pursue one of the biggest mysteries in ALS ­— how mutations in the C9ORF72 gene cause the most common genetic form of ALS.

“Dr. McPherson offered me many projects, but I chose to work on this one because it’s exciting to work on an open question,” said Kumar. “This project has the potential to discover new insights that may help scientists develop new treatments that are relevant for a large number of people with ALS.”

Improving lab methods

In 2011, scientists discovered that mutations in a gene called C9ORF72 are the most common genetic cause of ALS. What is known so far is that people with these mutations make less C9ORF72 protein while also making toxic substances in their motor neurons. But exactly how these contribute to causing ALS is unknown. To determine the possible role for how reduced levels of C9ORF72 protein might cause disease, one must first understand the normal function of the protein.

A few years ago, Dr. Carl Laflamme, who was working in Dr. McPherson’s lab, discovered that methods used to detect C9ORF72 protein in some previous studies were flawed. Supported by a 2016 ALS Canada Trainee Award, and an initiative called the ALS Reproducible Antibody Platform, which is co-funded by ALS Canada, the ALS Association (US) and the MND Association (UK), he used corrected methods with validated antibodies. He found that C9ORF72 protein was very concentrated in macrophages, a type of white blood cell. The word “macrophages” comes from the Greek word that means “big eaters,” an appropriate name for these cells that detect, surround and digest pathogens and cellular debris.

Building on this work, Kumar recently co-authored a scientific paper that shares best practices for using validated antibodies in ALS research with the whole ALS research community. He collaborated on the paper with Dr. Laflamme, Dr. McPherson and other ALS researchers at McGill University, the University of Toronto and the University of Oxford. It was published in October 2019.

Seeking answers to the C9ORF72 mystery

Kumar suspects that since C9ORF72 protein is largely detected in macrophages, it likely plays an important role in these cells. He thinks the role involves controlling the ability to digest pathogens and cellular debris: if the C9ORF72 protein levels decrease, the normal ability of the macrophages to clear out pathogen from our system may be affected. As macrophages are one of the guardians of the immune system, a dysfunction in the system might be related to the motor neuron degeneration in ALS.

To test his theory, Kumar will use validated antibodies to conduct a series of experiments to assess the quantity and activity of C9ORF72 protein using blood samples donated from families with familial ALS. He will also be using a new lab technique he created that can assess protein quantity and function from inside cells. If the loss of normal function of C9ORF72 protein does play a part in ALS disease processes, the insight may transform the approach for developing ALS treatments in the future.

Since he joined the McPherson lab, Kumar has enjoyed mastering complex lab techniques and brainstorming new ideas with colleagues. He attended the last two annual ALS Canada Research Forums in Toronto where he had the opportunity to meet people living with ALS.

“I’m a basic cell biologist. Meeting patients has given me a unique insight and appreciation for the disease,” Kumar said. “I always have the bigger picture of the patient in mind when I’m conducting my experiments. That gives me a push to keep going.”

The ALS Canada Research Program 

This funding represents one of 16 grants and awards we provided in 2019 through the ALS Canada Research Program, which is the only dedicated source of funding for ALS research in Canada. The three-year award will contribute to Kumar’s salary.

ALS Canada Trainee Awards support Canada’s emerging ALS researchers, whether they are doctoral students, postdoctoral researchers, or clinical research fellows. Trainee awards encourage young researchers to choose ALS as their area of focus, helping to ensure that Canada has a strong base of talented ALS researchers today and into the future. They also ensure that important ALS work is being pursued by high quality young scientists.

The funding of the project followed a rigorous scientific assessment by a panel of ALS experts. The panellists evaluated a larger pool of applications to identify applicants that demonstrate scientific excellence and have the potential to most quickly advance the field of ALS research in order to develop effective treatments.

ALS Canada is a registered charity that receives no government funding. Everything we do – from funding research to providing community-based support for people living with ALS – is possible only because of donor generosity and partnerships with provincial ALS Societies who contribute to the ALS Canada Research Program.

Because of you, the ALS Canada Research Program can continue to fuel the scientific discoveries that further our understanding of ALS. Your support makes a difference.

Please consider making a donation to help create a future without ALS.

Posted in: Research