Dr. Natasha Snider has several titles … doctor, researcher, genius (our words not hers) … but our favorite is climber. Dr. Snider is one person supporting Grayson’s Ladder in our climb to a cure, and she’s among the group of professionals currently looking for a drug to treat Alexander Disease. Her work has huge implications for Grayson, and for those with other rare diseases. Learn a little about her and the work she’s doing to test a drug in a short Q&A.
Tell me a little about yourself. I know you work at UNC Chapel Hill and that you study more than one rare disease. What’s your focus?
I am an assistant professor in the Department of Cell Biology and Physiology at UNC in Chapel Hill, where I started my independent research group three years ago. We are exploring mechanisms, and promising therapeutic avenues, for liver diseases and disorders linked to intermediate filament gene mutations.
How did you start researching a drug for Alexander Disease?
Dr. Albee Messing and Dr. Michael Brenner discovered in 2001 that AxD is caused by a mutation in a single gene. The mutated gene encodes an intermediate filament protein, which is my area of expertise and a topic I have been studying for the past 9 years.
So what does cause AxD?
AxD is caused by a toxic accumulation of the intermediate filament protein GFAP. That accumulation occurs in astrocytes, which are critical cells for the developing and mature brain. Astrocytes are relatively unknown and unexplored, but the short of it is if we can solve the GFAP problem in astrocytes, there are implications for other rare and common diseases.
Knowing that, how is your lab working to fix it?
We are building on >20 years of work on AxD that has led to the identification of important disease targets. In addition, we are very fortunate to be working on this right now, because we can take advantage of some major technological advances that have occurred in recent years and apply these advances directly to AxD. Our specific goal is to find an existing drug, or design a new drug, to block the toxic function of the mutant GFAP protein.
We are doing this by:
1. Studying FDA-approved drugs (currently there are ~1400 approved drugs). If we find a promising drug among this group, it has potential to significantly shorten the time that it would take to get that drug to AxD patients. This would be done by a process called ‘drug repurposing’ or ‘drug repositioning’.
2. Testing compounds that are currently in development but have not been approved yet. My lab is specifically interested in a class of drugs called ‘kinase inhibitors’, which are being developed mostly for cancer and neurodegenerative diseases. Tapping into this category of drugs significantly expands the scope of biological targets and chemical structures that we are studying for AxD.
3. New drug discovery. This is very much needed in our field - something that scientists who are studying intermediate filaments have been exploring for over 40 years but has been difficult to get at. For me, it is the most exciting part of what we are doing, but it is a high risk-high reward endeavor that requires various expertise, partnering with chemistry companies, etc. If we can show that we can ‘fix’ GFAP with a drug in an animal model, it provides a proof of concept to target other orphan diseases that share similar biology with AxD.
How can regular people help with this work?
To continue progress, we need to continue testing, gathering more data, and so on – but that takes resources – people to do the work, and funds to keep the momentum going. Since Alexander Disease isn’t as prevalent as other diseases, it can be difficult to get grants, but every little grant or donation through organizations like Grayson’s Ladder, or Elise’s Corner or United Leukodystrophy Fund helps us get leverage when we go to bigger organizations to ask for funding. With more support, we can train more graduate assistants, obtain key reagents and supplies for our labs, and more of what we need to test drugs.
About Dr. Snider
Where she works:
University of North Carolina at Chapel Hill
Department of Cell Biology and Physiology
Dr. Snider’s lab (www.sniderlab.com) studies the molecular basis of liver diseases and disorders linked to intermediate filament gene mutations. Her team uses biochemical, cell-based and in vivo approaches to identify potential disease targets and to understand their function and regulation. The major goal of Dr. Snider’s work is to promote the discovery of pharmacological agents that can slow or halt the progression of these diseases.