Katie Schultz joined the FARA team, as the Patient Engagement Director, in early February. Katie serves as a liaison between the patient community and other FARA stakeholders such as the pharmaceutical industry, academic scientists, and governing bodies to promote understanding of the FA condition and incorporation of FA families in research. Katie brings experience in investment management and biotech industry as well as training as a Genetic Counselor to the effort. Some of Katie’s FARA initiatives include upgrading the FA Global Patient Registry, working with the Ambassador Program and assisting with preparations for the upcoming Patient Focused Drug Development meeting. Katie recently had the opportunity to visit the labs of some FARA Funded Researchers and meet members of the FA community. Her blog about these visits and her learnings follows below.
Dr. David Corey’s Lab at University of Texas, Southwestern Medical Center, Dallas – February 2017
It was exciting to meet Dr. David Corey and his colleagues and tour his lab at University of Texas Southwestern Medical Center. We were able see firsthand the research that they are doing with patient skin cells. FARA Executive Director, Jen Farmer and I gathered with Eric & Lisa Dagely and their sons Jason and Alex, Linda DeSanders and her son Spencer Wright, and David Henry and his parents Dave & Karen, to hear about Dr. Corey’s incredible work researching ways to increase frataxin and to experience life in the lab.
Frataxin, a critical protein for normally functioning cells, is reduced in people with FA causing its devastating symptoms. With the cooperation of FA patients who have contributed their own cells from skin biopsies, this team has used a class of molecules called Oligonucleotides (Oligos for short) to show that they can help increase Frataxin in FA cells in culture. Normally, to make a human protein, the DNA (our genetic material) must first make RNA (a slightly modified copy of the DNA). The RNA then makes proteins that are important for our bodies to function properly. In FA, three letters of DNA in the Frataxin gene, ‘GAA’, are repeated hundreds to thousands of times, interrupting the normal process for making the Frataxin protein. Dr. Corey’s team has shown that Oligos can bind to the cell’s RNA, causing the level of Frataxin to increase!
Adding to this excitement, the FDA recently approved a drug for another disease (Spinal Muscular Atrophy) that incorporates an Oligo-based approach to restore a protein in infants who would otherwise die in infancy. And while this drug will not treat FA, it is proof that cells in the central nervous system, including the brain, can successfully be penetrated by an oligo drug. This is crucial for SMA and FA, both neurodegenerative diseases. Biotech and pharma companies are more likely to invest in drug development for diseases that use the SMA approach because there is data to show the approach has worked, and the approach has been reviewed and approved by the FDA. While there is still a lot more work to be done to show this approach is effective in FA animal models before moving into humans, it is an important approach to treatment and candidate in the treatment pipeline.
Dr. Marek Napierala’s Lab at the University of Alabama at Birmingham- February 2017
Can you imagine a way to grow and transform the skin cells from actual FA patients into any other type of cell, like neuronal or cardiac cells, which are critical for FA research? Drs. Marek Napierala and Jill Butler and their team at the University of Alabama at Birmingham are doing just that. And where do they get those skin cells? From you via Dr. Dave Lynch’s lab at CHOP! Once the skin cells arrive at Dr. Napierala's lab, the team uses a very precise “recipe” to prepare them so they can become stem cells, which then can be transformed into heart cells or neurons and other tissue specific cells important for all FA researchers to study the disease. One of those researchers is Dr. Corey, who could not do his experiments without the cells provided by Dr. Napierala’s lab. The key to successfully finding a treatment/cure for FA is partnership and collaboration. Without you, there would be no skin cells, and without Dr. Napierala’s team, there would be no processed research material for Dr. Corey and other FA scientists to do their important work. (View a live tour of Dr. Napierala's lab HERE.)
In addition to keeping a large repository of cells that are provided free of charge to any researcher involved in FA, Dr. Napierala’s team is working on advancing our understanding of how the GAA repeats silence the gene from making Frataxin, and they are making mouse models with large GAA repeats and the G130V point mutation seen in FA patients. Experiments using these mice will help identify potential biomarkers and better understand changes in gene and protein expression so that effective drugs can be developed. The team has recently seen some encouraging results showing that the expanded GAA repeat can be shortened with “genetic scissors”, increasing the level of Frataxin protein by several-fold. This is just the beginning, but an important early model for understanding how the approach might be used in humans one day. Thank you to the team for offering us more insight into how this process works and for hosting the viewing of “The Ataxian” with many of your colleagues and local families!