The Deater Foundation, Inc. Newsletter June 2022

The Deater Foundation introduces a new logo and a revised website for 2022. We continue to live out our mission providing information and support to persons with Hereditary Sensory and Autonomic Neuropathy Type1 (HSAN1) while funding medical research to discover a treatment and cure.

Scientists have finally mapped an entire human genome, nearly two decades after researchers first announced that they had sequenced the majority of the roughly 3 billion letters contained in human DNA.

Though the Human Genome Project was hailed worldwide when it was completed in 2003, at the time, many sections of the genome still couldn’t be placed. The new work — achieved by a consortium of scientists led by the National Human Genome Research Institute, the University of California, Santa Cruz and the University of Washington in Seattle — finally fills in the last 8% of DNA letters, or base pairs, that had no home in the sequence before.

The new genome paves the way to a better understanding of how people’s DNA can differ and how genetic mutations can contribute to disease. The scientists published their findings March 31 in the journal Science. www.LiveScience.com

When DNA letters are mis-matched, mutations occur.

Each cell in the human body contains all the information needed to make a whole person. This information is stored in the nucleus of the cell in material called DNA. Each person inherits half his DNA from his mother and half from his father. There are millions of ways the combinations of DNA can be put together, making each person unique.

The DNA is arranged into chromosomes and organized on the chromosomes into genes. Genes make proteins, and proteins make enzymes. Genes control how the body looks and functions. The chemical building blocks of a gene can be likened to the letters in a word. Like children’s letter blocks, each block represents a specific letter. If one of the blocks, or letters, is out of place the whole word, or gene, can be altered. For example, CAT can become HAT. Just as a sentence containing an incorrect word will make no sense, the cell doesn’t recognize the incorrect “word.” For example, “The hat jumped onto the table.”

The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and

more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences.

DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules

forming the vertical sidepieces of the ladder. MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 19 January 2021; cited April 30, 2022]. Available from: https://medlineplus.gov/.

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Dr. Robert H. Brown Jr.’s lab in Boston co-reported the discovery of the

genetic defect that causes HSAN1, jointly with Dr. Garth Nicholson in Australia.

Twenty-five years ago,

They mapped the gene for HSAN1 to chromosome 9q22 in families in Australia, the United States, and Canada. Many members of the Deater family participated in this study.

Subsequent research published by Dr. Brown’s team in 2001 identified the gene which is mutated in HSAN1 as one that encodes a sub-unit of serine palmitoyltransferase (SPTLC1). “In [the Deater family] replaces at position 398 and is predicted to substitute [the amino acid] tyrosine for [the amino acid] cysteine at residue 133 of the protein (C133Y).” The team also “detected a second mutation in a Canadian HSN1 family in which replaces at position 399, predicting substitution of tryptophan for cysteine (C133W).” Brown, R.H., Bejaoui, K. et al; Nature Genetics, Vol. 27, March 2001

Many other mutations have since been identified in the genes encoding subunits of the enzyme SPT and resulting in HSAN1.

www.deaterfoundation.org http://godfi.org

HSAN1 studies in Dr. Brown’s Laboratory, UMass Chan Medical School

T. H. Chan School of Medicine at the University of Massachusetts
Robert H. Brown, Jr. M.D., DPhil.

Studies of therapeutic approaches to HSAN1 have continued at UMass Chan Medical School, led by graduate student Huiya Yang in Dr. Bob Brown’s laboratory. This program has entailed two components. One is generating a strain of mice that have the Deater family mutation (C133Y). This entails a “knock-in” strategy in which the critical mutation is placed in the mice. The team is pleased to report that after months of work, and ultimately a contract with an

outside mouse facility, they now have the Deater mouse in hand. A key component of this effort is now characterizing the mice to determine if, as the mice age, they develop a neuropathy and also if they have the characteristic molecular findings in the blood and tissues (the presence of deoxysphingoid lipids).

The development of the C133Y mouse was funded by the Deater Foundation,Inc. Deater Foundation funding has been extremely helpful for us and is deeply appreciated.

A second component of the program is developing the anti-sense oligonucleotides to reduce production of the offending lipids. As reported previously, the strategy for that involves anti- sense oligonucleotides, or ASOs, that suppress the mutant gene (or a combination of the mutant and normal gene). Over the last year, Huiya Yang has generated a series of ASOs that suppress the key gene (called SPTLC1) in either the mutant, or mutant and normal, forms. She has raised one family of such ASOs that are intended to work in the mouse model and another that works in fibroblasts cultured from Deater family members.

The long-term hope is that these ASOs will be effective in suppressing SPTLC1 and will be non-toxic in animal models, which are key steps in the pathway toward a human clinical trial. As always, the UMassChan team is honored to work with the Deater family and the Deater Foundation and looks forward to an exciting year to come.





HSAN1 Symposium scheduled for 2022

An international conference on HSAN1 and related disorders, funded by the Deater Foundation, was planned in 2019 and scheduled for May 2020. And then: Covid.

The symposium was rescheduled and then postponed again. Two more attempts at scheduling occurred in 2021. Finally! There is a firm date for a virtual HSAN1 Symposium on Friday and Saturday, September 9 and 10, 2022! Because it will be held virtually, everyone who is interested will be able to attend. More information will be available on the Foundation website.

“Save the Date” invitations have gone out to selected presenters. We look forward to hearing about the work that is being done on many different fronts to combat HSAN1.

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WELCOME

We welcome you to the revised Deater Foundation website.

It is easy to access using either of the web addresses on the bottom of this Newsletter. Type into your browser: Deaterfoundation.org or simply “go” to goDFI.org. Better yet, save one of the addresses as one of your “favorites” and proceed with ease the next time you want to view what’s new. And right now, there is a lot that’s new!

You will see the information (included in this Newsletter) about the new Medical and Scientific Advisory Board. We are so very grateful to the physicians and scientists who have volunteered to support the Deater Foundation by meeting periodically to review current research and trends in HSAN1 studies so we can stay informed.

We encourage participation in the new HSAN1 Registry

Equally important, the website includes a portal to a secure registry at the University of Massachusetts Chan Medical School. We encourage anyone with any version of HSAN1 and those caring for someone with HSAN1 to enter some basic information into this registry.

The purpose of the Registry it two-fold. First, researchers seeking to initiate a new study or treatment trial will have access to a data base of people with HSAN1. Second, if you agree to be contacted, you will have the opportunity to join a study to further knowledge of the disease or possibly engage in a treatment trial.

Dr. Robert H. Brown, Jr. will have exclusive access to this information. A number (DFI#) will be assigned to use instead of a name to de-personalize the information. Dr. Brown will evaluate any researcher seeking information on persons with HSAN1 for potential participation in research and clinical trials. Individuals who have indicated interest will be contacted by the researcher. Those of you who participated in the various L-serine studies will recognize the possible benefits of such studies. Any registered person will have the right to choose the information they wish to share and to participate or decline inclusion in any study or therapeutic trial. Together, we can work to advance knowledge about HSAN1.

The Deater Foundation, Inc. owes a great debt of gratitude to Dixie Dorward Morgan, a member of the Deater family, who developed the website and supported it as a volunteer for many years.

Lionel Lynner Design and Creative, the new website manager, has 15+ years of experience in graphic design. Lionel will maintain the website as we continue to include more information.

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Beulah Deater Womer

Beulah Deater Womer was born in 1933, the youngest of the 12 children of
Alvin and Ellen Wilson Deater. She grew up in a household of love and faith
and the presence of a debilitating neuro-muscular disease, HSAN1. Her father
had lost both his legs to complications from the disease. Antibiotics were not
yet available in the early 1900’s, so injury and a subsequent infection often led
to an untreatable infection of the bone (osteomyelitis). Still, wearing wooden
prosthetics or a “peg leg”, Alvin ran his butcher shop in Noxen, Pennsylvania
and was well thought of and respected. When his hands became affected, and he could no longer maintain the butcher shop, Alvin drove a school bus and kept a big garden to support his family.

Nicknamed “Boot”, as the “caboose” of the succession of children, Beulah has very early memories of her brothers Harvey and Russell spending time in the Jefferson Medical College Hospital in Philadelphia where they had volunteered to be research subjects for the study of their rare and un-named disease. She recalls the letters Harvey wrote frequently to his mother- there were no telephones- to let everyone know how they were doing and what tests they were undergoing, always with a positive attitude. Harvey and Russell each had both legs amputated below the knee and learned to walk with their wooden legs. Boot has fond memories of their determination and good humor when they returned to the family home.

All the kids in the area walked barefoot in the summer. Walking to the swimming hole in Bowman’s Creek in those days meant walking along the railroad tracks on rough rocks under the ties. By the time she was in her teens, Boot’s feet were extremely sensitive, and she had to hang on to the other kids to make her way along those stones. In her early twenties Boot recognized the loss of feeling in her feet. She burned her feet twice without knowing. Once taking a hot casserole to someone, she set it by her foot in the car and was burned. Another time she sat too close to a register at church. When she found a tack in her foot that she had not felt, she knew she had the disease.

Boot says that for a little while she was devastated, but only for a little while. She had the example of “those who came before”- others in the family who were living with the disease. Besides the sister who had died, three brothers and two sisters also had what we now call HSAN1. Her disease remained stable for many years until she was about 60 years old. Since then, the disease has more profoundly affected her balance and her hands. She needs to be very careful especially with cooking, even using the microwave.

Boot is very proud of her extended family, those that have the disease and those that support them. “We are all very close.” She is grateful that God gave those who are affected mates who are helpful and considerate.

Boot’s life is rich with memories of caring and humor. She recalls when Russell was dancing in the house and kicked up his leg, only to have his prosthesis fly off and him to collapse, laughing, on the floor! And the time he got his leg stuck in the trolly door and the driver kept

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telling him to move to the rear, but he couldn’t because he was stuck!. Her brother Tom, also a bilateral amputee, learned to ride a bicycle wearing his prostheses.

Of course, there were sad times, too, like when her sister Verna who was 4 years older, was going blind and at the same time losing feeling in her hands. (editor’s note: We now know that HSAN1 and macular telangiectasia are related) Their mother encouraged her by giving her a plaque with the maxim, “Today is the tomorrow you worried about yesterday.”

Boot has met with various physician researchers and participated in a number of studies on HSAN1. She remembers when Dr. Tocantins who did the original research on her brothers, came to visit. Dr. McKechnie did a follow-up study. She traveled to the National Institutes of Health and Massachusetts General Hospital for tests. She hosted doctors from California and Germany in her home. She assisted Dr. Khemissa Bejaoui and Dr. Robert Brown, Jr. in their work by providing family history.

Boot says her back is very sensitive now. “When someone washes my back or puts cream on it, it just about kills me.” So she anticipates that she will be losing sensation there. Her husband died 3 years ago and she lives alone now, with family coming in to help.

She says “We were brought up with the ability to cope and to do whatever can, with the faith that my Mother and Grandma Deater instilled in us and the strength we saw in my Dad. I am blessed. God is still with me.”

♥♥♥♥ ♥♥♥♥ ♥♥♥♥ ♥♥♥♥ ♥♥♥♥ ♥♥♥♥ ♥♥♥♥ ♥♥♥♥ ♥♥♥♥ ♥♥♥♥ ♥♥♥♥ ♥♥♥

You Can Help Us Find a Cure!

The Deater Foundation exists thanks to the vision of members of the family who saw the need and opportunity to support research to find a treatment and cure for HSAN1. Family members have been involved in research for more than 80 years. The Foundation was established in 1990.

The Foundation continues to thrive thanks to the donations, large and small, of regular people. Family members and friends, people with a heart for those who are suffering, individuals who understand there is little funding for so called “orphan diseases” all contribute to the Foundation and help it to maintain this work. This year the Foundation will sponsor an international video symposium and will support a new initiative in collaboration with faithful researchers.

Knowledge in the fields of genetics and neuroscience is expanding day by day. We know there is a cure just over the horizon. We invite you to join with us to alleviate the suffering of those affected and prevent the disease in future generations.

Deater Foundation Inc Treasurer’s Report

Just a quick reminder that the Amazon Smile program is a super easy way to support DFI while you shop online! If you frequently shop on Amazon, please consider going through Amazon Smile and select DFI as your preferred 501c3 before you check out. A small percentage is donated with every order, and it all adds up! To date, DFI has collected $1,128.81…just from everyday purchases. And a big thank you to everyone who’s already been using this program to support DFI. Keep on shopping! 😊

Practical Tip from Chris

If you have HSAN1 you very likely develop callouses on various body parts. Sometimes wounds develop under the callouses. Sometimes callouses surround the wound as it heals. Amope is a device that keeps the callous under control by gently
sanding off the dead skin.

I personally use it on my heels and hands, this saves me a lot of
money as I previously saw a doctor at $40 a visit to debride the dead
skin. It is rechargeable and the grinder wheel is
replaceable. It can be used wet or dry. The price for the Amope Wet
and Dry Rechargable Foot File TM is about $40.
Be sure to keep it moving over the callous as you use it so you don’t injure good tissue.

Christine Deater Christensen

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Medical and Scientific Advisory Board

A Medical and Scientific Advisory Board has been established to support the Deater Foundation. Dr. Robert H. Brown, Jr., who has worked with the Deater family since 1978 will Chair the Advisory Board. Others who have graciously volunteered to serve include Dr. Florian Eichler, who has worked with the Deater Foundation since he was a post- doctoral member of Dr. Brown’s Laboratory; and Dr. Teresa Dunn, who was instrumental in identifying the mechanism of the HSAN1 gene defect. The board will meet once or twice a year to review new developments in areas related to HSAN1 and will inform the Deater Foundation Board who will disseminate that information. The Board is extremely grateful for their interest and involvement.

Dr. Florian Eichler is a pediatric neurogeneticist at Massachusetts General Hospital, with wide experiences in approaches to therapy for disabling
pediatric neurological disorders. He studies abnormal accumulation of lipids
such as very long chain fatty acids and deoxysphingoid bases. His lab
explores the relationship of mutant genes to specific biochemical defects
and their contribution to neurodegeneration. His clinical research studies
have defined disease progression in adrenoleukodystrophy, metachromatic leukodystrophy and Tay Sachs Disease. His work with Dr. Brown and
others showed that levels of deoxysphingoid bases in mice and humans with HSAN1 contribute to the disease and can be lowered by supplementation with L-serine.

Dr. Teresa Dunn-Giroux is a professor and Chair of the Biochemistry Department at the Uniformed Services University of the Health Sciences. She has had a long-standing interest in sphingolipids which are critical

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Dr. Robert Brown‘s laboratory at the University of Massachusetts Chan

Medical School has focused on the identification of gene defects that explain

the molecular pathogenesis of selected neuromuscular diseases including

amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease),

muscular dystrophy, adrenoleukodystrophy, and hereditary sensory and

autonomic neuropathy. His lab co-reported the discovery of the genetic defect

that causes HSAN1, jointly with Dr. Garth Nicholson. Knowledge of these

disease genes has facilitated the creation of mouse and cell-based models of

these disorders. In turn, these resources have allowed study of

treatment strategies, recently including biological therapies.

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proper development and function of the nervous system. A focus of her

to neurodegenerative diseases. A primary goal of her laboratory is to link

for

lab is to understand how mutations that alter sphingolipid synthesis lead

understanding of the biochemical basis of these diseases to therapy

development. Her work on sphingolipids was essential to the institution of

the L-serine trials and supplementation in HSAN1.

www.deaterfoundation.org http://godfi.org

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Come join us!

The 33rd Annual DFI Business Meeting is scheduled to be held remotely via Zoom on Friday July 15, 2022 at 7pm (EDT).

All are welcome to attend! If interested, please email us at deaterfoundation@yahoo.com prior to that date for the link information.

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Deater Foundation, Inc. PO Box 255
White Deer PA 17887

www.deaterfoundation.org

http://godfi.org

The Deater Family Reunion will be held on Saturday, July 16 at 12 noon behind Leroy and Isabelle’s house, 143 Stonetown Rd, Noxen, PA

Pot Luck -everyone bring food for their family plus some extra. It all gets put out on the food table for everyone to share. People coming from out of state please buy a bag of chips or cookies or such. Bring your own plates, utensils, drinks, and cups.

All are welcome!