Genes, Stem cells and Alpha-synuclein: An Interview with APDA Researcher Dr. Vikram Khurana

Our A Closer Look blog is designed to educate, inform and inspire you through a variety of topics and insights about Parkinson’s disease (PD). Our Interview with APDA Researchers series within the blog was created to give you a closer look at some of the dedicated APDA-funded researchers who are focused on finding better treatments and a cure for PD. Today’s installment introduces you to Dr. Vikram Khurana, Chief of the Division of Movement Disorders at Brigham and Women’s Hospital and Harvard Medical School in Boston, where he also leads the Dr. B.R. and Dr. C.R. Shetty Initiative in Parkinsonian Disorders. Dr. Khurana is a co-founder of Yumanity Therapeutics, a company that recently put its first potential drug for PD into clinical trial. He is the recipient of APDA’s prestigious George C. Cotzias Fellowship for the years 2019-2022. His current research focuses on stem-cell technologies and how they can be used to develop diagnostic and therapeutic strategies for PD and related disorders.

We asked Dr. Khurana questions about his stem cell research:

Q: What is the overarching goal of your research? What do you hope to find out?

A: Our goal is to develop patient-targeted therapies for PD and related disorders. We believe that diseases like PD are heterogeneous, and that a one-size-fits-all strategy may not work for development of treatment. We want to develop an understanding of what drives disease in particular patients, so we can better match them to a therapy that works for them.

On the basic science side, we study the protein that aggregates in PD called alpha-synuclein, and we look at what it does in the cell and how it disturbs cell biology when it misfolds. We study it intensely because classic PD always involves the aggregation of this protein. And so we think unlocking its mysteries at the cellular level will allow us to better understand how it ends up aggregating and causing neurodegenerative disease in a particular patient.

Q: Could you describe how you perform your studies?

A: From a blood sample, we sequence the DNA of our patients, and from a small skin biopsy we make stem-cell models from them too. From the stem-cells we make different cell types in the lab, including neurons and glial cells. Theoretically, we can use these cells, which are actually like a patient’s own brain cells and identify the key genetic “drivers” of neuronal dysfunction. In practice, since this approach is really so new, we begin these studies in specific patients that we think are highly informative, especially those who have mutations in the alpha-synuclein gene. We use these stem-cell models, and simpler cellular models also, to understand the biology of the alpha-synuclein protein.

Q: Can you tell us a little bit about what you have found out so far?

A: We have uncovered early defects within neurons derived from patients with PD and found methods to reverse those defects. Our discovery platform has enabled the identification of new potential drug targets, and our first potential treatment that emerged from this work is now in clinical trial, which we’re very excited about.

At the cellular level, we have identified many genes that influence directly or indirectly the response of the cell to alpha-synuclein toxicity. These gene “maps” have enabled us to uncover new biology of alpha-synuclein (a key project that is now being supported by the APDA Cotzias award).They are also being actively used in our lab to tackle a central problem, namely how specific gene defects may make individual patients more susceptible to alpha-synuclein toxicity.

Q: What fuels your passion for your Parkinson’s research?

A: There’s nothing quite like discovering something new! And engaging in that discovery process with a terrific group of lab members and collaborators is a joy. But most of all, my patients and their caregivers inspire me to keep going. It’s a privilege to practice medicine and to run a lab that enables me to directly perform research relevant to my patients. And yet, it’s also disheartening not to yet be able to offer a patient anything beyond symptomatic treatment. That of course is all we currently have for PD and other related disorders that I care deeply about like multiple system atrophy. We have to be able to do better and my lab is trying to develop ways to do better! 

Tips & takeaways:

  • Important PD research is constantly taking place across the APDA network.
  • Khurana is a recipient of an APDA’s Cotzias research grant for the years 2019-2021. Read more about all of the current research APDA is funding.
  • Khurana works to understand how genetic mutations in PD affect the cellular processes that cause PD.
  • We are only able to fund this research because we receive donations from dedicated people like you. If you would like to support this critical work, please consider a donation to fund Parkinson’s research.

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