2022 Emerging Investigators

Chenxu Li

Bio

Chenxu Li is currently a PhD student from the Department of Experimental and Clinical Pharmacology at the University of Minnesota Twin Cities. Chenxu earned her BS degree in Pharmaceutical Analysis from Shenyang Pharmaceutical University in 2019. Upon graduation, she continued research as a graduate student and earned her MS degree in Pharmaceutics from the University of Minnesota in 2021. Soon after, she began investigating novel therapies for adrenoleukodystrophy as a PhD student under the supervision of Dr. Reena Kartha.

Project: Nervonic Acid-A Potential Therapeutic Targeting Mitochondrial Dysfunction and Cellular Oxidative Stress

Mutations in the adrenoleukodystrophy (ALD) protein result in the accumulation of very long chain fatty acids (VLCFAs), which in turn causes the elevation of harmful substances including reactive oxygen species. This can also further damage other cellular components such as the mitochondria, the energy source of the cells. Chenxu’s research mainly focuses on developing novel therapies for ALD, specifically targeting the effect of these toxic chemicals on mitochondria. She will investigate the mechanism of Nervonic Acid (NA), a dietary fatty acid, that can arrest or delay disease progression in ALD. By treating cells derived from patients with ALD using NA, this study will investigate how NA can mitigate the toxic chemicals and positively affect energy production in cells. Her hope is to develop NA as a safe and effective dietary intervention that can benefit all individuals with ALD.

April Rickle

Bio

April Rickle was born and raised in New Jersey. She attended Rutgers University- New Brunswick for her undergraduate studies where she worked in the Vershon lab studying Sir2 protein cofactor interactions in baker’s yeast. April graduated in 2019 with a BA in Molecular Biology and Biochemistry and joined Van Andel Institute Graduate School for her doctoral studies. There, she joined the Lempradl lab and began her work studying ALD via a fruit fly model of the disease. She hopes to continue researching rare diseases throughout her career. In her spare time, April enjoys spending time with her cats, crafting, and baking.

Project: Testing the impact of the drug leriglitazone in a fruit fly model of ALD

Leriglitazone (MIN-102) is the lead candidate in Minoryx’s pipeline. It is a promising new compound for the treatment of ALD. Previous research has been done in cell culture, mice, and in a clinical trial, but we do not fully understand how it affects the brain. We will treat a fruit fly model of ALD with leriglitazone and test how it affects movement and behavior; brain tissue degeneration; metabolism; and gene expression. By testing the effects of leriglitazone on our ALD model flies and comparing to our healthy flies, we can determine which aspects of disease leriglitazone treats and how it affects them. In addition, examining these factors in healthy and untreated ALD model flies will give us insight to the molecular mechanisms behind ALD overall. Doing this research will give us a better understanding of how leriglitazone treats ALD, as well as how ALD works in a broader sense.

Hemmo Yska, MD

Bio

Hemmo Yska is a PhD candidate at the Amsterdam University Medical Centers in the Netherlands. After becoming a medical doctor, he worked as a resident in pediatrics. Due to his interest in scientific research and (pediatric) neurology, he decided to pursue a PhD where he (mainly) focuses on clinical research in the field of ALD and other leukodystrophies. Currently, together with the other members of the Dutch ALD group, he is involved in a number of projects that, for example, focus on the addition of ALD to the newborn screening and the identification of surrogate outcomes for spinal cord disease.

Project: Attitudes of patients towards sex-specific ALD newborn screening

Males with X-linked adrenoleukodystrophy (ALD) are at risk for developing adrenal insufficiency and/or progressive leukodystrophy (cerebral ALD) at an early age. Newborn screening (NBS) for ALD enables pre-symptomatic monitoring and therapeutic intervention, thereby preventing irreversible damage and saving lives. ALD has been included in NBS programs in more than 25 US states and several European countries are considering its addition. As girls are not at risk for developing the childhood cerebral form of ALD, some countries are reluctant to screen them for ALD. Sex-specific screening has not yet been implemented in newborn screening and there is limited scientific data regarding the attitude of patients to screening males only. In order to make a well-informed decision it is important to understand the attitudes of all groups and stakeholders that are involved in the disease. Therefore, a group that cannot be overlooked is the ALD patients themselves. Patients and their direct relatives can provide valuable insights on matters such as sex-specific screening and the potential burden of knowledge of a late-onset disease. With our study, we would like to learn whether ALD patients feel that boys only, both boys and girls or neither should be screened for the disease. In order to investigate this, we will send out a questionnaire to members of “the Dutch ALD cohort” and their relatives. The results will be of importance to all countries that are considering the addition of ALD to their NBS.