Brain Tissue Donation: A Crucial Way to Advance PWS Therapies

brain-tissue-donation-a-crucial-way-to-advance-pws-therapiesFPWR is partnering with Autism BrainNet to collect and study post-mortem brain donations. Through  this partnership, we aim to raise awareness about the importance of post-mortem brain donation, streamline the donation process for families, and enhance the collection and distribution of high-quality tissue to researchers. 



Why is donating brain tissue important to research and therapeutic development in PWS?

Our understanding of Prader-Willi syndrome (PWS) is advancing, but not as quickly as we, scientists and families, would want. One challenge is that the direct study of disorders that affect the brain, like PWS, is more difficult than disorders affecting other organs. While the development of models that mimic some aspects of PWS including cell and animal models have greatly advanced our understanding of the syndrome and have been critical for screening potential therapeutics before they are being tested in patients, there is no substitute for studying human brain tissue to unravel the complexities of the brain neurocircuitry defects in PWS.

Brain donation is critically important. Relative to donations of other organs for transplantation and/or research, brain donation is severely lagging, especially from children. “If we want better interventions, we need to look for neuropathology and find patterns of cell pathology.” says Dr. Patrick Hof, Icahn School of Medicine. "We need to build a significant research resource of donated brain tissue."

More information on brain tissue donation is available on the Autism BrainNet website.

Register As A Tissue Donor

There Is No Substitute for Studying Brain Tissue

Live brain imaging techniques allow studying many aspects of the neurobiology of hyperphagia, cognition or other behaviors in individuals with PWS. Neuroimaging includes the use of various techniques to image the structure, function, or pharmacology of the nervous system. Although techniques are evolving at a fast pace allowing analyses with greater spatial and temporal resolution, they are limited for characterization of cellular structure. Study of post-mortem brain tissue gives unique information as exemplified by the work of Dr. Hof and collaborators funded by FPWR on structure of the brain in PWS.

Using brain tissue, Dr. Hof and his team are examining von Economo neurons (VENs) in the frontal lobe where executive function for decision making, sensory perception and social behavior reside. The VENs are implicated in several neuropsychiatric illnesses such as fronto-temporal dementia, schizophrenia and autism and are thought to play a role in empathy, social awareness, and self-control.Many of the phenotypic characteristics of PWS are consistent with abnormalities of the autonomic system involving functions supported by VENs. These neurons are found in higher primates, elephants and cetaceans whose survival requires social communication; they cannot be studied in mouse models of PWS. Examining whether VENs number or cellular function could be altered in PWS can only be done in post-mortem brain tissues.

The knowledge derived from quantitative neuroanatomical studies of postmortem human tissue from patients with PWS brings critical information to better understand brain function abnormalities in PWS and open new therapeutics avenues. Oxytocin therapies currently under development in PWS is a good example of that. A study published in 1995 of post-mortem brains from individuals with PWS by Swaab, et al., gave the first indication that the number of oxytocin neurons may be reduced in PWS. Complementary studies in mouse models of PWS have helped further define the nature of oxytocin deficits in PWS and are helping to guide clinical development. The therapeutic development of oxytocin in PWS also illustrates how postmortem studies are particularly useful for informing animal and cellular models, which can then be used to explore the underlying mechanisms and consequences of molecular aberrations on behavior, brain function or neurochemistry.

"Research on the human brain structure and pathology is essential," says Dr. Hof. "Even if much can be learned from models and from brain imaging studies of patients, the examination of postmortem brains is the only way to analyze disease pathology at any level of resolution and across disciplines, and this is why brain donation is so important. We have learned immensely about conditions like Alzheimer's disease and schizophrenia from brain donations. The same must be accomplished for rare diseases for which mechanisms are not always elucidated and no animal models exist."

Quality Brain Tissue is Critical for Research

Postmortem brain studies have been used to understand the relation between the brain, behavior and diseases for centuries. The sensitivity and specificity required for molecular measures are, however, greater today and rely on high tissue quality. This requires not only collecting better tissue than before, but also identifying measures of tissue quality and setting quality thresholds. Unlike animal tissue, whose condition at death can be controlled and influenced, human tissue can only be collected naturalistically.

This introduces potential confounds, based both on pre- and postmortem conditions, that may influence the quality of tissue and its ability to yield accurate results. Amongst the traditionally recognized confounds that can reduce tissue quality, postmortem interval, tissue collection and tissue processing are critical. Tools to assess tissue quality parameters are still evolving and stress the importance to have highly qualified expert teams to handle brain tissue collection and processing.

The Gift of Tissue Will Last Beyond a Lifetime

One of the most valuable contributions to research a person or family can make is to volunteer for a brain donation program. While samples of some bodily tissues can easily be obtained at the time of a scheduled surgery, brain tissue is only available after an individual’s death and must be obtained and preserved within hours of death to be useful to researchers. This requires planning and a prompt decision from the individual’s family as well as a major coordination of effort from the brain bank staff. Because it is an emotionally difficult and personal topic to consider, gathering prior information and allow ample time for discussion with family members is important for making a decision at a very difficult time.

Partnering with Autism BrainNet

Autism BrainNet is a collaborative network of academic sites that collects, stores and distributes brain tissue for research on autism spectrum disorders. This brain bank is intended to support the highest-quality and most rigorous research into the underlying genetic and neuropathological mechanisms that contribute to autism and related neurodevelopmental disorders such as PWS.

The network is funded by the Simons Foundation and is directed by Professor David Amaral, a distinguished neuroanatomist and research director of the MIND institute at the University of California, Davis. Autism BrainNet has established several partnerships with non-profit organizations to develop a unified approach for brain banking for autism and related neurodevelopmental disorders. These include partnering with the NIH NeuroBioBank, the Dup15q Alliance, the Phelan-McDermind Syndrome Foundation and more recently FPWR. Autism BrainNet has received over 100 donations since it began collecting tissue in June 2014.

Tissue collection and storage is carried out at four regional nodes across the United States: Sacramento (University of California, Davis), Dallas (University of Texas Southwestern Medical Center), Boston (Harvard Beth Israel Hospital) and New York City (Icahn School of Medicine at Mount Sinai directed by Dr. Hof) and an international node in the United Kingdom (the Oxford Brain Bank at Oxford University). Tissue distribution is overseen by a scientific review committee that comprises members of the FPWR research team who will review request for PWS brain tissue to ensure that brain tissue applications are scientifically meritorious and relevant to PWS.

Brain tissue recovery is coordinated nationally by Autism BrainNet. A 24-hour hotline number is available for families for further information on the donation process or for brain donation. The team at Autism BrainNet will also follow up after the donation occurs to schedule a visit with the donor’s family. The purpose of this visit is to collect essential documentation about the donor and to learn more about the donor’s background. Donation can still be arranged even if families have not pre-registered. The Autism BrainNet will assume all costs related to tissue recovery.

FPWR's partnership with the Autism BrainNet will enable the highest quality brain tissue collection, storage and distribution to the PWS research community, be a valuable resource for researchers interested in PWS and in other-related disorders while ensuring the smoothest process for families in difficult times. 

For questions regarding the brain tissue donation process, please call Autism BrainNet at this 24-hour toll-free number: 877-333-0999, or visit the website by clicking here or below.

Register As A Tissue Donor

Topics: Research

Nathalie Kayadjanian


Nathalie Kayadjanian, Ph.D is an expert in translational biomedical research. A neuroscientist by training, she has extensive R&D experience in academia, biotech, and the pharmaceutical industry in Europe and the USA. Nathalie has occupied top management positions in patient-driven non-profit organizations, developing and implementing strategies to accelerate the development of innovative therapies for rare diseases.

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