Tag: Patient Research

Snapshot: What is Cerebrospinal Fluid (CSF)?

Public transit may not be the first thing that comes to mind when we think about the brain, but it’s a great way to understand how all the parts of the central nervous system work together. Nutrients, hormones, and other important molecules (the passengers) need to get on and off at different stations to do their work. They might first stop at the large internal chambers within the brain, called ventricles. From the ventricles, they can get to the central canal in the spinal cord, as well as the subarachnoid space. The subarachnoid space is a space between two membranes that surround the brain and spinal cord. It provides a stable structure for a network of veins and arteries.

The passengers are shuttled from station to station by the cerebrospinal fluid (CSF), a clear, colourless fluid that provides the central nervous system with necessary nutrients and hormones while carrying away waste products. CSF also cushions the brain and spinal cord by circulating between layers of tissues surrounding them. The whole public transit system is enclosed: the subarachnoid space and the ventricles are connected to the central canal in the spinal cord, forming a single reservoir for CSF.

Cerebrospinal fluid written in colorful letters under a Stethoscope on wooden background
Photo used under license by Sohel Parvez Haque/Shutterstock.com.

CSF is made by the choroid plexus, a collection of tiny blood vessels called capillaries. Capillaries filter the blood and secrete it into the ventricles. When the pressure of CSF is less than the pressure in the capillaries, CSF flows out and into the ventricles. When the pressure of CSF is greater than that of the bloodstream, the extra fluid is absorbed from the subarachnoid space and into sinuses (large areas filled with blood), where it can flow into the surrounding veins. The blood supply in the central nervous system tightly regulates the movement of molecules or cells between the blood and brain. This blood-brain barrier is crucial for protecting the brain from toxins and pathogens. Dysfunction of this specific system contributes to the development of neurological diseases.

Anatomical labeled scheme with human head and inside of skull, including superior sigittal sinus, ventricles, arachnoid Villi and spinal cord central canal.
Structure of the ventricles and central canal components that contribute to the public transit system. Photo used under license by VectorMine/Shutterstock.com.

Why is CSF Important for Neurodegenerative Diseases?

In neurodegenerative diseases like Spinocerebellar Ataxias, CSF contains molecules that can be used as biomarkers. Biomarkers are disease-specific proteins that change in concentration depending on disease stages. Biomarkers provide information on disease progression, with or without the impact of therapeutics. They are also crucial for understanding how disease processes work and assist in developing treatments.

The development of intrathecal injections, injecting into the central canal for distribution to the central nervous system (for example, spinal anesthesia), has been monumental for administering drugs in neurodegenerative diseases. In other words, not only can the public transit system of the central nervous system be investigated to see what passengers are associated with the disease, but it can be used to deliver “medicine passengers” to the place where the disease occurs.

If you would like to learn more about Cerebrospinal Fluid, take a look at these resources by MedlinePlus and WebMD.

Snapshot written by Kaitlyn Neuman and edited by Dr. Tamara Maiuri.

Spotlight: The CMRR Ataxia Imaging Team

Location: University of Minnesota, MN, USA

Year Research Group Founded:  2008

What disease areas do you research?

What models and techniques do you use?

A photo of the CMRR Ataxia Imaging Team
A photo of the CMRR Ataxia Imaging Team in 2019. Front row, left to right – Diane Hutter, Christophe Lenglet (PI), Gulin Oz (PI), Katie Gundry, Jayashree Chandrasekaran Back row, left to right: Brian Hanna, James Joers, Pramod Pisharady, Kathryn France, Pierre-Gilles Henry (PI), Dinesh Deelchand, Young Woo Park, Isaac Adanyeguh (insert)

Research Group Focus

What shared research questions is your group investigating?

We use high field, multi-nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS) to explore how diseases impact the central nervous system. These changes can be structural, functional, biochemical and metabolic alterations. For example, we apply advanced MRI and MRS methods in neurodegenerative diseases and diabetes.

We also lead efforts in research taking place at multiple different cities across the United States and the world. As you can imagine, studies spread out across such a big area require a lot of coordination and standardization. We design robust MRI and MRS methods to be used in clinical settings like these.

Another important question for our team is how early microstructural, chemical and functional changes can be detected in the brain and spinal cord by these advanced MR methods. We are interested in looking at these changes across all stages of disease.

Why does your group do this research?

The methods we use (MRI and MRS) can provide very helpful information to be used in clinical trials. These biomarkers we look at can provide quantitative information about how a disease is progressing or changing.

There is good evidence that subtle changes in the brain can be detected by these advanced MR technologies even before patients start having symptoms. If we better understand the earliest changes that are happening in the brain, this can in turn enable interventions at a very early stage. For example, we could treat people even before brain degeneration starts to take place.

Why did you form a research group connecting multiple labs?

We came together to form the CMRR Ataxia Imaging Team to benefit from our shared and complementary expertise, experience, and personnel. We can do more together than we could apart.

Are you recruiting human participants for research?

Yes, we are! We are looking for participants for multiple different studies. You can learn more about the research we are recruiting for at the following links: READISCA,  TRACK-FA, NAF Studies, and FARA Studies. More information is also available through the UMN Ataxia Center.

A photo of the CMRR Ataxia Imaging Team in 2016
A photo of the CMRR Ataxia Imaging Team in 2016, in front of the historic 4T scanner where the first functional MR images were obtained, in CMRR courtyard. Left to right – Christophe Lenglet (PI), Sarah Larson, Gulin Oz (PI), Dinesh Deelchand, Pierre-Gilles Henry (PI), James Joers, Diane Hutter

What Labs Make Up the CMRR Ataxia Imaging Team?

The Oz Lab

Principal Investigator:  Dr. Gulin Oz

Year Founded:  2006

Our focus is on MR spectroscopy, specifically neurochemistry and metabolism studies. We focus on spinocerebellar ataxias. Also, we have been leading MRS technology harmonization across different sites and vendors.

The Henry Lab

Principal Investigator: Dr. Pierre-Gilles Henry

Year Founded:  2006

We develop advanced methods for MR spectroscopy and motion correction. Then apply these new methods to the study of biochemistry and metabolism in the brain and spinal cord in various diseases. We have been working on ataxias since 2014.

Fun Fact about the Henry Lab: The French language can often be heard in discussions in our lab!

The Lenglet Lab

Principal Investigator:  Dr. Christophe Lenglet

Year Founded:  2011

We develop mathematical and computational strategies for human brain and spinal cord connectivity mapping. We do this using high field MRI. Our research aims at better understanding the central nervous system anatomical and functional connectivity. We are especially interested in looking at this in the context of neurological and neurodegenerative diseases.

Fun Fact

Members of our team have their roots in 7 countries (US, Turkey, France, India, Mauritius, South Korea, Ghana) and 4 continents (North America, Europe, Asia, Africa)

For More Information, check out the Center for Magnetic Resonance Research (CMRR) Website!

Written by Dr. Gulin Oz, Dr. Pierre-Gilles Henry, and Dr. Christophe Lenglet, Edited by Celeste Suart

Spotlight: The Kuo Lab

Principal Investigator: Dr. Sheng-Han Kuo

Location: Columbia University, New York, NY, United States

Year Founded:  2012

What disease areas do you research?

What models and techniques do you use?

Kuo Lab group photo.
This is a group picture of the Kuo Lab. From the left to right: Nadia Amokrane, Chi-Ying (Roy) Lin, Sara Radmard, Sheng-Han Kuo (PI), Chih-Chun (Charles) Lin, Odane Liu, Chun-Lun Ni , Meng-Ling Chen, Natasha Desai, David Ruff.

Research Focus

What is your research about?

We study how mishaps and damage in the cerebellum lead to the symptoms experienced by ataxia and tremor patients. By looking at human brains, as well as brains from mouse models, we study how different changes in brain structure can lead to symptoms. This includes how well different parts of the brain can communicate with each other.

Why do you do this research?

When you ask patients about the challenges living with ataxia or tremor, they will talk to you about their symptoms. Symptoms can make different activities of daily living very challenging! By connecting specific brain changes to specific symptoms, we want to develop treatment options that target specific diseases. By doing this, we hope to improve patient’s quality of life. 

Initiative for Columbia Ataxia and Tremor Logo. It is a circle containing a lion with its whiskers to look like a neuron

The Kuo lab is part of the Initiative for Columbia Ataxia and Tremor. It’s a new Initiative at Columbia University to bring a group of physicians, scientists, surgeons, and engineers to advance the knowledge of the cerebellum and to develop effective therapies for ataxia and tremor.

Are you recruiting human participants for research?

Yes, we are! We are looking for participants for clinical research and trials. You can learn more about the studies we are currently recruiting for at this link.

Fun Fact

In the Kuo Lab, we call ourselves “the Protector of the Cerebellum in New York City”.

For More Information, check out the Kuo Lab Website!

We are looking for new graduate students and postdoctoral researchers to join our team. If you are interested in our work, please reach out to us

Written by Dr. Sheng-Han Kuo, Edited by Celeste Suart

Spotlight: The Zoghbi Lab

Baylor College of Medicine

Principal Investigator: Dr. Huda Zoghbi

Location: Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, USA

Year Founded:  1988

Logo: Texas Children's Hospital. Jan and Dan Duncan Neurological Research Institute

What disease areas do you research?

What models and techniques do you use?

Research Focus

What is your research about?

Our laboratory uses multiple methods to explore the underlying causes of different neurodegenerative and neurodevelopmental disorders. Some diseases we study affect children, like Rett Syndrome. Others affect adults, like spinocerebellar ataxia type 1 (SCA1), Alzheimer’s disease (AD) and Parkinson’s disease (PD). We also research how healthy brains grow and develop.

We first seek to understand the mechanism by which a mutant protein causes disease, allowing us to more thoughtfully and effectively develop therapeutic options for the diseases we study. Our work in SCA1 demonstrated that lowering levels of the disease-driving protein is beneficial in the course of disease, informing our approach to the study of other diseases of the brain.  

Why do you do this research?

We do this research to help the patients, families and caregivers affected by the diseases we study. Most of the disorders we study currently have no or very few treatment options available, and we hope to help in changing that.

Our lab began with Dr. Zoghbi seeing patients in the clinic who were diagnosed with Rett Syndrome and SCA1. Work with these patients allowed for the discovery of the genes causing these diseases. Today, we hope to aid in understanding how these diseases work and to develop therapies that can then be brought back to the clinic for patients. Furthermore, we hope our findings and the tools we’ve developed will aid in the study of other neurodevelopmental and neurodegenerative disorders.

A group picture of the Zoghbi Lab
Zoghbi Lab members at Hermann Park in Houston, TX in 2021. Bottom row L-R: Y. Sun, W. Wang, W. Lee, M. Zaghlula, H. Lee, S. Coffin, S. Wu, J. Butts, C. Adamski, H. Zoghbi (PI), Y. Shao, J. Johnson, J. Zhou, A. Tewari, H. Palikarana Tirumala, J. Lopez, Top row L-R: A. Anderson, E. Xhako, E. Villavicencio, Y. Li, S. Bajikar, M. Durham.

Fun Fact

On April 8, 1993, both Dr. Huda Zoghbi and Dr. Harry Orr identified the gene, ATXN1, which when mutated, is responsible for causing SCA1. You can read about this discovery here.

For More Information, check out the Zoghbi Lab website!

Written by Stephanie Coffin, Edited by Celeste Suart

Elongating expansions in HD and SCA1

Written by Dr. Marija Cvetanovic  Edited by Dr. Larissa Nitschke

Expanded CAG repeats are the cause of Huntington’s disease (HD) and several spinocerebellar ataxias (SCAs). Longer inherited CAG expansions correlate with the earlier disease onset and worse symptoms. We know from past research that these expansions are unstable and become longer from one generation to the next.

This study by Mouro Pinto and colleagues shows that repeat expansions also keep getting longer throughout life in patients affected with HD and SCA1 in many cells, including brain, muscle, and liver cells.

Expansion of CAG repeats in different human genes cause several neurodegenerative diseases. This includes Huntington’s disease (HD) and several spinocerebellar ataxias (SCAs). These long CAG repeats in disease genes tend to be unstable in the sperm and egg cells. This instability in sperm and egg cells can result in either longer repeat tracts (expansions) or shorter ones (contractions) in the children of affected patients. Unfortunately, CAG repeats more often expand than shrink. This results in a worse disease in the affected children, with earlier onset and more severe symptoms than their parents.

However, repeat instability and expansion of repeats are not confined to the sperm and egg cells. It can occur in many cells in a patient’s body. This ongoing expansion that occurs in other body cells is called somatic expansion.

Abstract background of DNA sequence
Long CAG repeats in disease genes can be unstable and expand. Photo used under license by Enzozo/Shutterstock.com.

As affected patients age, the ongoing somatic expansion, especially in the brain, may accelerate the onset of neuronal dysfunction and loss of neurons and. This may worsen the disease progression. This has been previously shown in mouse models and patients with HD. However, those studies examined expansion in only a few brain regions and tissues outside the brain (called peripheral tissues).

In this study lead by Dr. Vanessa C. Wheeler, the authors systematically examined repeat instability in 26 different regions of the brain, post-mortem cerebrospinal fluid (CSF) and nine peripheral tissues, including testis and ovaries from seven patients with HD and one patient with SCA1.

Continue reading “Elongating expansions in HD and SCA1”