Back to Basics: Combatting Rare and Neglected Diseases

University researchers partner with pharmaceutical companies to develop novel therapeutics

The mosquito is responsible for most deaths each year; why? Malaria. According to the Centers of Disease Control and Prevention, in 2013 alone, malaria caused 198 million clinical episodes and 500,000 deaths, not including deaths in which malaria is a secondary cause. While antimalaria drugs are on the market, for many, the cost or availability prevents adequate healthcare. Dr. Kasturi Haldar, Parsons-Quinn Director of the Boler-Parseghian Center for Rare and Neglected Diseases and Professor of Biological Sciences at the University of Notre Dame, studies the fundamental mechanisms that underpin malaria and other neglected and rare diseases and that lead to novel targets and therapies. Her efforts affect the many patients often left uncared for due to a disease of poverty or the rarity of their disease and the lack of fundamental research to support therapeutic interventions.

To accelerate the development of therapies, Dr. Haldar and her team partner with pharmaceutical companies in innovative models of private public partnerships. For instance, she has signed a collaborative agreement with Eli Lilly & Co for drug discovery and development for any rare or neglected disease. Dr. Haldar’s research therefore fills a niche that pharmaceutical companies cannot, without non-profit collaboration, and furthermore creates a sustained impact upon the global community. Additionally, Dr. Haldar combines efforts with a large number of collaborators across all continents (other than the Arctic and Antarctic), who provide clinical samples and specific components of technology for her laboratory work. In so doing, she has relationships across the globe that are able to make impacts in their regional communities that improve health outcomes and gather diverse datasets. It is Dr. Haldar’s hope to develop therapies that will provide life-saving solutions for diseases that typically don’t fit the pharmaceutical model and continues to motivate her to contribute to medicine and science. Thankfully, through her innovative partnerships, robust collaborations, and rigorous research, Dr. Haldar’s research has provided an effective and efficient method of adding to the dialogue surrounding rare and neglected diseases and disorders.

Current research includes:

  • Malaria Medication Resistance: Dr. Haldar’s research on malaria focuses on mechanisms by which the parasite infects and survives in blood cells to cause all the symptoms and pathologies of malaria. Despite the reduction of global malaria burdens, children and adults -- especially in sub-Saharan Africa -- are dying at startling and unacceptable rates. With most deaths being caused by the human malaria parasite, Plasmodium falciparum, resistance of this organism to artemisinins threatens malarial treatment, control and elimination. Dr. Haldar and her team are investigating the recently discovered molecular mechanisms of artemisinin resistance for Plasmodium falciparum. In doing so, Dr. Haldar hopes to use new knowledge to develop therapies that will circumvent resistance.

  • Severe Disease: Dr. Haldar studies mechanisms of severe disease caused by malaria, which lead to organ failure and death, in order to identify predictive indicators to signal 1-2% of high risk patients. By identifying patients, Dr. Haldar hopes to advance the ways in which they can be monitored on in-patient basis to greatly improve their chances of survival.

  • Rare Lysosomal Disorders: Focused on repurposing FDA approved drugs to treat neurological diseases by improving access across the blood brain barrier and developing plasma markers for neurodegeneration, Dr. Haldar’s work in rare lysosomal disorders is making impressive progress in an area of extreme need. This translational research has the potential to impact those affected by these inherited and harmful disorders. Although each rare disease affects a small number of patients, since there are ~7000 of them, in aggregate 1:10 americans (and people worldwide) suffer from a rare disease.

Bio

Perhaps the most important influence for Dr. Haldar’s professional trajectory was her family. Her father was a nuclear chemist while her mother was a mathematician. Therefore, as a child growing up in India, she was surrounded by the sciences and understood its profound power for transformation. As she advanced through school, Dr. Haldar continued to develop her love for discovery and science. She has since found it to be a terrific way to be part of a very important societal endeavor while still retaining a ‘normal’ personal life.

In her malaria work Dr. Haldar began by studying secretion from the parasite to the red cell and investigating the parasite’s Golgi, This led to understanding that the parasite was not just secreting cargo to the red blood cell, it was also releasing an entire sub-compartment of its rather rudimentary Golgi. Indeed, the parasite commits a large proportion of its genetic composition to secreting and remodeling the red cell, This lead to new fundamental biology, mechanisms of pathogenesis, the and pursuit of discovery of therapeutic strategies (since the parasite is getting increasingly drug resistant) as well as collaborations with major pharmaceutical companies like Eli Lilly & Co and private product partnerships like the Medicines for Malaria Venture.

Her work in rare genetic disorders (initiated over the last five years) was driven by the invariably fatal outcome that faces the small community of patients struck by the rare neurological disease Niemann Pick Type C (NPC). Therefore armed with genomics, she repurposes existing drugs to improve the treatment of disease. This has led to establishment of a small pharmaceutical company NPC therapeutics LLC whose goal is to develop treatments for NPC and other neurological disorders, since monogenetic rare disorders such as NPC provide powerful portals into more prevalent multigenic disorders like Alzheimer’s and Parkinsons. They may also provide insights into the spread of Ebola in the recent outbreak, since the virus uses the NPC1 protein to infect host cells (and deficiency in NPC1 protects against infection).

Website: http://www3.nd.edu/~crnd/directors_page.html

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