Monday, September 21, 2026

Fayuvi (rebisufligene etisparvovec-hopf) for treatment of mucopolysaccharidosis type IIIA (Sanfilippo type A)

Courtesy of a colleague

The U.S. Food and Drug Administration today approved Fayuvi (rebisufligene etisparvovec-hopf), the first treatment for pediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A., MPS IIIA is a rare inherited disease that progressively damages the brain and nervous system, causing children to lose cognitive, language and other developmental abilities over time. Until today, treatment was limited to managing symptoms; there was no FDA-approved therapy designed to change the underlying course of the disease.

"The Trump Administration is committed to bringing safe and effective treatments to patients with the most urgent and unmet needs. The approval of Fayuvi marks a historic moment for children and families living with MPS IIIA, which is a disease that has, until now, offered no approved treatment to alter its devastating course,” said Acting FDA Commissioner Kyle Diamantas, J.D. “Gene therapy holds tremendous promise for rare diseases like Sanfilippo syndrome type A, and this milestone reflects the FDA's commitment to action.”

Fayuvi is a one-time, intravenous (given directly into a vein) gene therapy that uses a modified, non-infectious virus called an adeno-associated virus serotype 9 (AAV9) to deliver a working copy of the SGSH gene into the patient’s cells. This enables the body’s cells to produce sulfamidase — the enzyme that is missing or deficient in MPS IIIA — allowing heparan sulfate to be properly broken down in lysosomes and reducing its harmful buildup throughout the body and brain.

“For families living with Sanfilippo syndrome type A, the trajectory of this disease is heartbreaking — children who develop normally in their earliest years facing a relentless regression with no approved treatment to slow it. Parents and clinicians have been waiting far too long for an option,” said Karim Mikhail, B. Pharm., M.S., Director of the Center for Biologics Evaluation and Research. “Today’s approval of Fayuvi is a meaningful step forward — not only for these children and their families, but for the promise of gene therapy to address rare and devastating diseases where the need for safe and effective treatment is the most urgent.”

The safety and effectiveness of Fayuvi was evaluated in an open-label, single-arm, multicenter clinical study in pediatric patients with MPS IIIA. The study measured mean changes in cognitive scores in patients between the ages of 2 and 5 years. Fayuvi-treated patients maintained or improved cognitive function compared to an untreated historical control cohort — a meaningful divergence from the expected natural disease course of plateau and decline during this critical developmental window.

“Achieving meaningful neurodevelopmental benefit through a single intravenous administration represents a significant scientific milestone — demonstrating that systemic AAV9-mediated gene delivery can reach the central nervous system at therapeutically relevant levels in pediatric patients. This approval underscore OTP’s and FDA’s commitment to applying rigorous evidentiary standards as the field of gene therapy continues to advance,” said Megha Kaushal, M.D., M.Sc., Acting Deputy Director of the Office of Therapeutic Products.

The safety of Fayuvi was evaluated in pediatric patients who received a single intravenous infusion across clinical studies. The most commonly adverse reactions reported in more than 5% of patients were increases in liver enzymes (AST), nausea and vomiting, fever, decreased appetite, decreased white blood cell and platelet counts and increased amylase. Important safety warnings include the risk of thrombotic microangiopathy (TMA). As with other AAV-based gene therapies, there is a potential long-term risk that the inserted genetic material could integrate into the genome and potentially lead to tumor development.

Fayuvi is administered in a healthcare setting equipped to manage infusion reactions. All patients receive corticosteroid treatment beginning one day before the infusion and continuing for a minimum of eight weeks afterward.

Fayuvi was granted Orphan Drug and Fast Track, and Breakthrough Therapy designations. The FDA granted Fayuvi approval to Ultragenyx Pharmaceutical, Inc.

https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-pediatric-patients-sanfilippo-syndrome-type







Protection, compassion, and care—not death presented as medical treatment

The family of an 83-year-old Canadian woman is demanding answers after she died through the country's medical assistance in dying program despite allegedly becoming distraught when told the procedure would end her life and showing signs of cognitive decline, according to a report.

The Daily Mail reported Sunday that an 83-year-old Christian grandmother, Brigitte Stegemann, was killed under Canada’s physician-assisted suicide program, called Medical Assistance in Dying (MAiD), on July 10.

Her granddaughter, Brigitte Kranendonk, said that she was her grandmother’s primary caregiver and that her family had decided to place Stegemann at The Pearl care home in Cannifton due to physical and mental decline.

But according to Kranendonk, her grandmother still had a good appetite even following a stomach cancer diagnosis, and rejected the idea of using MAiD when it was presented as an option.


Everything changed, however, in June when Kranendonk left to go on a 10-day road trip with her husband.

Kranendonk said she remained in regular contact with the care home and was told her grandmother had fallen and would need a wheelchair, but said she was not initially alerted to any dramatic decline.

Then, on July 3, near the end of her trip, Kranendonk said she received a call informing her that the home planned to arrange a MAiD assessment for Stegemann, despite her grandmother previously telling her that she did not want an assisted death.

Kranendonk said, according to The Daily Mail, that when she returned, she asked a nurse at The Pearl about who had initiated the MAiD conversation.

"The nurse became very abrasive, very defensive," Kranendonk told The Daily Mail. "She was like, ‘Well, I’m just trying to advocate for her. I’m just trying to do what’s right for her.’"

After returning from her trip, Kranendonk said she found out her grandmother had already had her first MAID consultation.

The granddaughter also alleged that Stegemann struggled during an assessment of her mental capacity, incorrectly answering questions about members of her own family.

Kranendonk said she was present for Stegemann's second MAID assesment, and said that the doctor used "really loose terms, never using the words death or dying."

"She explains MAID to my grandmother by saying: 'We’re going to give you medicine, you’re going to feel at peace. And I just want you to know that you won’t have a bowel movement,'" Kranendonk said.

When Kranendonk interjected and said, "She doesn’t understand what you’re saying," the doctor allegedly looked at Stegemann and said, "We’re going to make sure you won’t have any more pain."

According to a doctor, Stegemann was "deemed fit for MAID, and we're going to proceed," The Daily Mail reported.

Kranendonk said that two days before Stegemann's death, she asked her grandmother directly whether she understood that the scheduled procedure meant she would die.

According to Kranendonk's account to the outlet, Stegemann began crying and said she had "made a mistake."

Stegemann was allegedly told by the doctor her grandmother could "deny" MAiD on the day of the procedure, but Stegemann was already unsure if her grandmother had actually consented to it, did not want to cause her more stress, and wanted to enjoy what could be the last few days she had left with her grandmother.

During the procedure, Kranendonk said the nurse who was administering the IV was not wearing gloves and had a hard time putting it into her right arm, piercing her grandmother many times, which resulted in "blood all over the place."

The doctor then came and told Stegemann she was there to give her "medicine," which she did not respond to.

"My Oma is not moving," Kranendonk said. "She doesn't open her eyes. She doesn't nod. She doesn't say anything, and the doctor just said: ‘Okay, well, I'm going to proceed.’"

Kranendonk said her grandmother was dead within 10 minutes.

Kranendonk said she wishes she would have applied for a legal injunction to stop the MAiD from occurring, but also said she was not aware she had the option.

She is appealing to the Chief Coroner’s Office in Ontario, as well as the Patient Ombudsman and Belleville Police, to investigate if what happened was legal.

According to the BBC, Canada’s MAID law, which legalized euthanasia in 2016, is responsible for one in every 20 deaths in Canada.

In a statement to Fox News Digital, Kranendonk said, "My grandmother was a vulnerable senior who was let down when the doctors and home bypassed every safeguard put in place to protect her — from assessing her mental capacity, to getting her clear, final consent before acting and the home filling out paperwork and having her sign when we were not there, and giving us copies. I will not stop until there is a full investigation into how this was allowed to happen behind closed doors."

Mira Metter, Director of "Broken Country," a film about the decline of the country over the last two decades, said in a statement to Fox News Digital, "What is particularly troubling about this case is that it raises questions Canadians should be asking about whether MAID’s safeguards are protecting vulnerable people as intended."

Metter added, "A compassionate healthcare system should ensure that when someone is at their most vulnerable, every reasonable avenue for care and support has been explored before death is presented as an option. MAID may be legal in Canada, but legality cannot be the end of the conversation."

Laura Echevarria, National Right to Life's communications director and press secretary, told Fox News Digital in a statement, "Euthanasia and assisted suicide cross a line medicine should never cross: from caring for patients to intentionally ending their lives. The most vulnerable among us deserve protection, compassion, and care—not death presented as medical treatment. No safeguard can undo a mistake once a patient is dead."

Fox News Digital reached out to The Pearl and Belleville Police for comment but did not immediately hear back. 

Rachel del Guidice 

https://www.foxnews.com/media/family-sounds-alarm-83-year-old-woman-dies-canadas-assisted-death-program

Tuesday, September 15, 2026

Emotional doulas/the last hug

For mothers whose babies lived only briefly—or never took a breath —remembrance can be both agony and gift. Meet the women who enter silent delivery rooms to help these mothers create the few precious memories that must last a lifetime: a whispered word, a photograph, one final hug

The Call

It’s 1:15 in the morning when Andrea Chattah’s phone rings.

“Hello?” she whispers into the darkness.

It’s the woman she spoke to hours earlier. Nothing was happening then, so Andrea told her to try to sleep, to call when the birth was progressing. Now the young mother is on the phone, and her voice is eerily flat.

“The nurse says it’s almost time,” she says.

Andrea sits up, hearing only silence on the other line. There’s no beeping fetal monitor in the background, and she can almost taste the sadness through the phone.

“Do you want me to come?” she asks gently.

“Yes.”

Andrea’s up, dressed, and on her way in minutes.

She’s not the only one who answers calls like this.

Andrea Chattah and Chany Lebovits are some of the approximately 75 women on call across the New York Tristate area, with another 35 in Israel. They do this work through an organization called Knafayim, founded by Malkie Klaristenfeld, and they call themselves “emotional doulas.”

For them, there’s no coaching a laboring woman toward a healthy delivery. No breathing exercises or positioning techniques or ice chips in flimsy plastic cups.

The emotional doulas are there when labor ends, not with a beautiful cry… but with silence. And these women show up, night and day, because no mother should have to give her child one last hug alone.

The Doing

“When it comes to helping a mother who’s having a stillbirth, the first thing everyone asks me is, ‘What do you do? What do you say?’”

That question, Malkie Klaristenfeld explains, is a fundamental misunderstanding of the emotional doula’s role. An emotional doula’s work is not to do, but to be there. There’s no hard-and-fast script for them to follow. Every family has its own dynamic, and every situation involving a baby who isn’t compatible with life or a stillbirth is different. Every mother walks into that hospital room with their own beliefs, relationships, and dreams.

The emotional doula is a presence. Sometimes she’s right beside the mother, sometimes she stands outside the door of the hospital room. Sometimes she talks, and sometimes she doesn’t speak at all. The most important thing a mother has to feel is that she wasn’t abandoned.

This is because a stillbirth is not only heartbreaking, but also a trauma for the mother.

“Even a mother who’s lost a baby before doesn’t ‘get used to it.’ Every loss is different, so the trauma and the crisis is real, every single time,” Malkie says.

And that’s where the emotional doulas come in.

From Malkie’s experience, whether or not a mother is able to move forward largely depends on whether she was emotionally “there” for what happened to her. When a mother feels like she was part of that experience, as devastating as it is, and when she was able to make decisions about what was happening, she can recover.

It’s difficult to move forward from something you never faced.

Unfortunately, for years, hospitals and families followed the opposite instinct. They wanted to “protect” the mother and keep her from seeing her child or facing the sadness of her situation. The prevailing attitude was one of forgetting, sweeping the incident under the rug, and turning the entire subject into a conspiracy of silence. What was the point of remembering, anyway? But it was a choice that left countless grieving mothers awakening later and asking, “What happened to me? What happened to my baby?”

The role of the emotional doula is not to remove pain, but to help each woman be fully present in the moment, to immerse themselves in the pain so it doesn’t haunt them later… and to memorize the moments of motherhood that will have to carry them through a lifetime.

Even during the worst hours of the night, the grieving mother who was present at the birth can at least say to herself: I was there. I know what happened.

The Hello That Means Goodbye

How do emotional doulas prepare for the situations they face?

Many regular doulas take initial training seminars that last from two to six days. But while this gives them a basic grounding in regular birth, such a short timeframe can’t come close to preparing emotional doulas for a stillbirth. This is why Malkie built a six-week training seminar for emotional doulas. Not everyone who trains is already a doula. Malkie opens the program to anyone — social workers, therapists, or people who just want to help.

First, trainees learn about the emotions and language of the silent delivery room, how to talk… and how not to. They discuss what birth looks like in these situations and model the different types of conversations that might come up, as well as appropriate responses.

Malkie repeats one phrase to her cohorts each year: Saying hello means saying goodbye.

Our first instinct is to look away from a loss, to tell ourselves out of sight, out of mind. But the ostrich-head-in-the-sand attitude doesn’t spare anyone. Looking, processing, and greeting the baby helps parents eventually have closure.

One more thing every emotional doula has to learn (and for some, the hardest lesson of the entire six weeks) is that your story is not their story, and it never gets to enter the room.

“I come to every case with my losses behind me,” Malkie says. “But their story has nothing to do with mine. I will never bring my life into another person’s experience.”

The training is designed to put a trainee into the delivery room, into the mind of a family that isn’t hers, while keeping her own past separate. Nothing she carries should ever become something a newly grieving mother has to carry, too.

Three Doorways

Most emotional doulas don’t come into this job by default.

Some suffered loss, or even multiple losses. Others watched loved ones face loss. Some women simply love to give to others. Every woman who becomes an emotional doula can point to the exact doorway she took on her way to this calling.

Malkie’s doorway was her own life. Nineteen losses — some early, some late. After suffering the agony of her tenth loss, she came to a realization. “I had two choices: bury myself in my pain, or do something with it.” She chose to “do something,” first working with another organization, and then building Knafayim to support mothers and families facing pregnancy and infant loss.

Andrea’s doorway opened seemingly by accident.

“My daughter was due in the middle of Covid, back when hospitals had begun letting certified doulas into delivery rooms. So I got certified in four days so I could be there for my daughter,” she explains.

Andrea was already a psychotherapist and a consultant for Sephardic Bikur Cholim’s fertility division, which helps families trying to have healthy babies. She trained with PSI (Postpartum Support International) to earn a Perinatal Mental Health Certification, and continues to learn through her supervision with Devorah Enten, one of her initial teachers, and who is the same supervisor Malkie uses to train Knafayim’s clinical doulas. This connection led her on the road to helping mothers during the pain of a stillbirth.

“I felt like I was doing Hashem’s work,” she says. “I still feel that way.”

Chany Lebovits’s doorway was her son, who saw an advertisement in a magazine about doula classes and sent it to her. Chany signed up, then learned about Knafayim’s course. For someone who loves giving to others, it wasn’t much of a choice. Terrified but game, Chany jumped into the unknown.

And this network of women doesn’t stop at the edge of the Tristate area or Israel.

When a woman in a small town in the Midwest was carrying a baby with a life-limiting diagnosis, Malkie didn’t have anyone nearby to send. Instead, she found a Chabad doula through a parallel network and made sure the young mother wouldn’t have to walk into labor alone.

Anywhere a mother faces loss, that’s where the emotional doula will stand by her side.

“We reach wherever we’re needed.”

The Hello

“By nine in the morning, I was screaming,” Baila begins. It was her third birth, but two healthy children hadn’t prepared her for the roller coaster of a pregnancy marked by medical complications… and then the shattering moment when the doctor told her the baby’s heart had stopped beating.

“People who know me could tell you I never scream or yell. Even when I was having my first, I never cried out.” But two days earlier, Baila learned her baby had already died, and the emotional doula who was supposed to meet her wasn’t there when the contractions suddenly became intense.

“I kept screaming that I wasn’t going to deliver this baby alone,” she remembers.

It’s the fear an emotional doula races against every time she gets the call. The hospital staff can manage the medical side of things, but no one wants a woman to go through the worst hour of her life with no one beside her.

Every story like Baila’s begins before a doula leaves her house. There’s a group chat for many of these emotional doulas, and usually Malkie posts the barest outline: 34 weeks, getting induced tonight, third pregnancy, or sixth pregnancy, should go quickly. Hands go up, and whoever’s closest or free or the best fit responds to the call.

Chany remembers the first time she responded, agreeing to be an emotional doula for a grieving couple. “I was terrified,” she says candidly. “I called Malkie in a panic and asked her, ‘What do I even say to these people?’ She told me, ‘Just be yourself.’”

Most of the doulas don’t need to rush to the hospital the moment a pregnancy loss is confirmed. One of the reasons for this is that the doulas aren’t needed for pain-management techniques through a grueling labor. In these births, an epidural is common, since the goal is to keep the mother as comfortable as possible.

“I was on an epidural the entire time,” Baila says. “But they warned me the labor could be very long, because a baby who isn’t alive can’t help the birth progress properly.”

If a woman just started labor, there’s little reason, most of the time, for an emotional doula to sit in the waiting room for eight hours.

“We usually don’t go in until labor is more active,” Andrea says.

When she does walk into a hospital room, she assesses the situation. What’s happening? Who’s present in the room? What emotions does she sense? Her first step is to address both the mother and father, validating their pain. She connects with them by asking if they have questions, tries to make them comfortable, and gently builds a relationship. Andrea tells them a little about herself and asks if it’s okay for her to sit down.

Often, the doula is the first person the family’s talked to since the devastating news.

“My role is to help them not feel so alone,” Andrea says. “There’s often a sense that people don’t want anyone to know, so in most cases, the couple comes into the hospital very alone.”

And if there are other relatives or people in the room, that can help… or make everything dramatically more complicated, especially if there are strong opinions about what the couple should do next. Sometimes Andrea will ask to speak with the couple alone to hear what they really want.

The family’s community, culture, and background often have a lot to do with how events play out. Couples from certain places or backgrounds often go through the loss by themselves. For them, this is a private moment of pain. For others, birth is often a time when the mother and mother-in-law are present, so there are more people in the hospital room. This could lead to more support or more arguing… and then the emotional doula’s job expands to navigating the family.

The emotional doula prepares parents for what comes next, for the unfamiliar moments after the baby is born, and for decisions the parents may never have imagined making.

And then there’s the birth itself.

Some of the mothers don’t even want to push, and the doula will validate her feelings and cry with her.

There’s a visceral fear that comes with picturing a baby — supposed to be at the beginning of life — together with death. But when a stillborn baby is delivered, Andrea doesn’t see what others might imagine.

“For me, it’s not scary, because I don’t see a baby who died. I see a baby who passed away,” she says. “I feel like there’s kedushah in the room, and a pure neshamah. It’s more spiritual than scary.” When she can, she holds the baby and says a perek of Tehillim into the stillness.

After that, the family is often moved to a separate room, usually at the end of a corridor, away from the maternity ward. And on the door of that room, in most hospitals, there’s a small, discreet marking — a butterfly or a wave — so that passing hospital staff knows what room this is.

“When I was there,” says Baila, “even the cleaning crew said to me, ‘I’m sorry for your loss.’”

The Hardest Goodbye

The hardest conversation when there’s a stillbirth or a baby who lives for only a short time after birth is whether or not the parents should see the baby.

Malkie remembers when an entire family arrived at the hospital together — the couple, both sets of parents, everyone walking into the delivery room at once. They found out together that there was no heartbeat. The devastation was total, and the family’s unanimous, immediate verdict was, “There’s no way she’s going to see the baby.”

That was when Malkie noticed the husband hadn’t said much, and she realized he wanted to see his son. She started talking, very gently, about the possibility of spending time with the baby when he was born.

After the birth was over, Malkie made sure the bereaved father was able to hold his baby and say his own private goodbye. The mother wasn’t ready, so Malkie asked her if she could take a picture of the baby.

“I’ll hold on to the photo,” she told the exhausted mother. “You don’t have to look at it now.”

A few weeks later, Malkie received a call.

“Can I have my baby’s picture?”

It was the only piece of her baby the mother would ever have.

When it comes to seeing the newborn, Malkie teaches that it’s important for emotional doulas to never force a mother into one enormous, irreversible decision. Instead, they give her a series of small ones, letting her take control in an accepting, nonjudgmental way.

First, the baby is cleaned and wrapped in the same blanket and hat every newborn receives. The emotional doula pauses behind the curtain in the room before bringing a baby in, gently saying out loud exactly what the parents can expect.

“I prepare them for what they might see,” Andrea says. “And parents can decide if they want to see the baby’s face… or not. When even a face feels like too much, there are less frightening connections for the mother — a footprint, a photograph of just the feet, even a single toe uncovered. And I always ask it as a question. Do you want to see his little foot? Do you want to stroke his hand?”

Chany’s learned to ease mothers into interacting with their babies in a comforting, nonthreatening way. One baby was born with a deformity, and instead of asking the mother to make a yes-or-no decision about whether to look at her, she started talking about the baby.

“I covered her and said, ‘Look at the baby, isn’t she tiny?’ The mother leaned in, kissed her, and held her little wrapped bundle.” When the baby was treated like a person, the whole process became easier. Chany always tells the mothers, “You don’t want to look back without closure. Hold the baby, even just for a few minutes.”

But it’s always a suggestion. Nothing is ever forced.

Andrea has watched this decision play out in every possible way. One mother chose not to hold her son. When that happens, Andrea gives the mother options, that Andrea can hold the baby, or look at the baby and report back. The mother wanted her to look at the baby for her.

“When I came back into the room, she asked me right away, ‘What color hair does he have? What does he look like?’ Maybe she didn’t want to hold him, but I remember thinking, That’s a mother!”

Some families choose the opposite, trying to make the time they have together as full and tender as possible. They sing to their baby, rock the tiny body gently, talk, and cry, trying to compress years of parenting into mere hours.

Andrea recalls a mother who wanted her stillborn daughter dressed in pink for photographs, “like a little photo shoot.” The nurses helped change the baby so they could take all the pictures she needed, granting a heartbroken mother the opportunity to acknowledge the loss of her daughter in a way that gave her comfort.

And when a young mother chose not to see her stillborn, Andrea asked the mother if Andrea herself could hold him. At least this mother would always know that someone held her child lovingly before he had to be taken away.

This time together matters because many parents are more connected to the baby than they realize. Mothers have already bonded with kicks and fluttery movements throughout the pregnancy. For them especially, holding the baby can be very therapeutic.

It’s also agony.

“When I had my stillborn son, I was very torn,” Baila admits. “I loved my baby and wanted to see him and hold him. But I was terrified of being haunted by some frightening image instead of picturing my baby the way I imagined him, adorable and angelic.”

While the baby was being taken care of, Baila’s emotional doula held her hand and talked to her softly. Then she went to see the baby for them.

“It’s a boy, and he’s so sweet,” she told them, then asked if they wanted her to bring him in.

“My husband looked at the baby first, and said he didn’t think I should look at the face, but he did think I should hold him. So that’s what I did. I held my baby with his face covered. Then my doula asked gently, ‘Should I uncover a little foot for you? Would you like that?’ I saw his precious toes, I cried, I talked to him, and I felt a sense of closure, even though I never saw his face.”

But not every baby is stillborn. Some of Chany’s most difficult calls are for babies who can’t live long.

“We go in for sick babies also, not just stillbirths,” she says. “Some babies only live for an hour, and we support those families, too.”

Most parents facing this situation already know before labor that this is where things are headed. There’s been a diagnosis and weeks of preparing for the inevitable. That doesn’t make the end any easier. The baby might be breathing normally one moment, and then suddenly, things change.

“It’s very hard,” Chany says.

The choice of having a healthy baby was taken away, so emotional doulas give the parents as many other options as possible. Because at the end of the day, what matters most isn’t whether a mother wants to hold her baby or not. It’s that nobody else makes the decision for her.

The Making of a Mother

All three women agree — grief goes looking for someone to blame.

There was a couple Chany helped out over Succos. They were staying at his parents when the wife realized she wasn’t feeling any movement. She called the doctor, who didn’t answer. She decided to wait until the next day before contacting him again. When she went into the office, there was no heartbeat.

Chany stayed with her during the long labor. When the stillborn baby girl was delivered, there was a tremendous feeling of grief in the room — and self-reproach. “Maybe I should have tried calling the doctor again, and the doctor should have answered…”“It’s very common for the mother to turn the blame on herself,” Chany says, “even though you can’t blame yourself for what’s only in Hashem’s Hands.” But self-blame takes something away from a woman. If it’s her fault that her baby died, what kind of mother is she? Is she considered a real mother? Maybe she didn’t take her vitamins, or she exercised too strenuously, or… the blame game can be an endless loop. A traumatized woman, one who can’t bring herself to hold the baby she feels she harmed, is often left wondering if she’s even allowed to grieve.

Making her a mother to the child gives something back.

“My fundamental belief, my passion, is to support the mother and make her a mother to this child, because when Mashiach comes, this is her child. However it happens, whatever form it takes. Becoming a mother and a father to this child, in whatever way is right for them, will validate their pain,” Malkie says.

As a psychotherapist, Andrea sees mothers who suffered through these traumatic births alone. She knows that some of those who don’t have the opportunity to process the loss can possibly develop symptoms of depression or anxiety later on. With acceptance of the child, the pain, and the circumstances — without any blame — comes a certain amount of comfort.

The Costs… and the Dividends

Being an emotional doula is not something Andrea or Chany blithely set down at the end of a shift.

For Andrea, being an emotional doula transformed her relationship with pregnancy. What she used to think of as a more “natural” occurrence has turned into profound reverence for the neis that is the creation of a child.

“Every cell dividing, every heartbeat starting, every toe and nail forming — a million things have to go right. And most of the time, amazingly, it does.” For her, Hashem is so clearly a partner in having a baby. “It’s a miracle every single time.”

For Chany, the change is subtle. “I’ve always loved helping people, but being an emotional doula has given me so much more sensitivity, and the ability to really see what another person needs.” When visiting a relative recovering from surgery, she realized intuitively that the woman needed a gentle touch, so she massaged the woman’s neck and shoulders.

“It was worth a million dollars to her,” Chany says. “Being an emotional doula helps cultivate that feeling, because I’m completely there for the mother — emotionally, mentally, and physically, for whatever she needs. I’m focused on her.”

And both women keep one foot planted in ordinary doula work. “Baruch Hashem, I get plenty of healthy births, too,” Chany says, “and that balance really helps.”

Sometimes, what carries an emotional doula through the pain is a note… which Chany has plenty of.

“Here’s one,” she says: “‘Your selflessness, coming to the hospital in the middle of the night to help people you didn’t even know, made our difficult situation so much easier. May Hashem shower you and your family with tremendous nachas, simchah, and all good things.’”

Still, emotional doulas are also human, and many of them also need to process their experiences. For this, Knafayim models peer-to-peer debriefing (not necessarily with a professional), totally centered on the doula herself. She can’t focus on what her clients went through, but on how she needs to find closure with what she saw and did.

The most beautiful moment? For Chany, that’s when the phone rings again, months or years later, with a different kind of news.

“I’m expecting, and I’d like you to be my doula at the birth.”

The privilege of bringing life into the world for a mother who once faced death is a wonderful, healing experience. And having an emotional doula at a live birth after loss is rewarding for the mother as well.

When Baila had her next child (another boy), she made sure to hire a doula who knew about loss.

“She understood my trauma. When it came time for labor and delivery, I kept asking her obsessively, ‘Is the baby okay? Is it really okay?’ And she told me, ‘Don’t worry, I’ll make sure this baby is going to cry so loudly when he’s born that you’ll want to cover your ears!’”

She knew that Baila couldn’t bear the sound of silence.

And Andrea, after helping too many grieving mothers, wants them to know: “You don’t have to go through this alone. Whether you have to terminate a pregnancy or your baby died in utero and you need to deliver… there’s help. I wish more people knew to reach out to organizations like Knafayim. We’re Klal Yisrael, we help one another. There’s always someone to call.”

The Last Hug

The last hug is the hardest.

Baila recalls how her emotional doula gave her and her husband space, stepping out of the hospital room and letting the two of them be alone with their baby.

“Even then, she peeked in to make sure we were okay,” Baila says. “My husband and I were crying and talking to the baby the whole time. Eventually, I felt like I would never stop crying as long as he was in my arms, and I let my doula know I was ready to send him back. She made sure I calmed down, that I ate and drank something — she literally brought me food! My husband had to step away to make phone calls, arranging for the chevra kaddisha, so she just sat with me.

“It might sound like, just an hour or two, is that really such a big deal? But for someone going through the trauma of a stillbirth, having someone really there for you, making sure you’re as okay as you can possibly be through the whole experience… it was everything.”

And then Baila and her husband had to face the journey home, arms achingly empty and hearts filled with grief.

“I davened that I should be the last Yiddishe Mama to go through this,” Baila says, and there’s a catch in her voice. Because her tefillah hasn’t been answered… yet.

Because during the day, and sometimes at night, the phones in the emotional doula group chat still buzz. There’s the information about a date, a hospital, a number of weeks. Then virtual hands fly up and a woman will go, because someone is about to become the mother to a child she’ll only hold once, and she needs someone to be there.

So they go. And they daven.

Let this be the last time. Let this be the last time a stillborn baby is held. Let this be the last time we hold a mother in her grief. And let this be the last time a mother has to give her child one last hug to carry her love into eternity.

Dos and Don’ts

Don’t say: “Baruch Hashem, you have a beautiful family at home.” “B’ezras Hashem, you’ll have another baby.” “You’re young, you’ll have more.” Andrea calls these her “top three least helpful comments.” Nobody grieving for one specific child wants to hear about the children they already have or the ones that might come down the line. Andrea’s started warning families in advance, before they leave the hospital: “People are going to say dumb things, and I want you to just say, ‘Baruch Hashem’ back, because Baruch Hashem, they don’t understand what you’re going through.”

Don’t forget the physical: After one woman’s third loss, Chany didn’t wait to be asked to do things. She brought the woman a blanket, slippers, water, and helped her get dressed after her procedure, down to her shoes and socks. After birth or a procedure, women need physical care just as much as emotional support.

Do open the conversation: This is the piece of advice Chany is proudest of. “After the birth, I tell the women to tell one trusted friend what happened, and let that friend tell everyone else so things don’t get awkward. Otherwise, people just avoid you.” It’s not out of cruelty, but because nobody knows what to say.

Do encourage something tangible: Andrea tells families they can buy or make something to honor the memory of their baby. She has her own memory piece, a necklace with a butterfly charm and a heart charm, bought years ago for a family member’s two losses.

Do let them write it down: Andrea suggests writing down what happened. “A mother who writes her story is able to put her thoughts into a story that is concrete and organized, and this can be very helpful in processing her loss and helping her heal.”

Do keep the photographs (even the ones nobody’s ready to see): Knafayim’s team keeps every photo on file indefinitely. “One family couldn’t look at their baby’s picture when I took it, but they called asking for it now, months after their loss,” says Malkie.

Shoshana Gross

https://mishpacha.com/the-last-hug-2/

Mitchell syndrome ACOX1 mutation

When a patient with puzzling neurological symptoms enrolled in the Undiagnosed Diseases Network, researchers led by Dr. Hugo J. Bellen were set on solving the mystery. The patient presented with an unidentified late-onset neurodegenerative disorder. The team named this new syndrome “Mitchell Syndrome” in reference to the first patient to be diagnosed with this disorder and looked to identify its genetic basis. “On comparing the patient’s and his parents’ DNA, the team identified a mutation in the patient that resulted in a single amino acid substitution (N237S) in the ACOX1 protein. This change was seen only in the patient and was not present in either of his parents’ DNA, indicating that the patient had a de novo, or new, mutation on this gene,’ said Bellen, professor at Baylor College of Medicine and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and also a Howard Hughes Medical Institute investigator. “With the help of the online gene-matching tool GeneMatcher, we found two more patients who had the same new mutation in the ACOX1 gene.”

All three patients, who ranged from 3 to 12 years old at the time of disease onset, had remarkably similar clinical features, including degeneration of peripheral nerves that caused a progressive loss of mobility and hearing. The three individuals had identical gene variants, a clear indication that ACOX1 dysfunction likely was the cause of the symptoms.

A medical mystery

The finding that an ACOX1 mutation was linked to Mitchell Syndrome initially baffled the researchers. The only known ACOX1-related disorder described in the medical literature at that time presented earlier in infancy with seizures, severe cognitive decline, neuro-inflammation and accumulation of very-long-chain-fatty acids in plasma and, more importantly, was caused by the lack of the ACOX1 protein – none of which was true for these three patients.

“The brain has large amounts of lipids, which are critical for the proper functioning of the nervous system. Abnormal breakdown of lipids in the brain and peripheral nervous system is associated with several neurodegenerative diseases,” Bellen said.

The gene ACOX1 is involved in lipid breakdown. It produces an enzyme called Acyl-CoA oxidase 1 that initiates a series of reactions that break down very-long-chain-fatty acids in small intracellular organelles called peroxisomes.

Fruit flies help solve the medical mystery

To resolve this conundrum, the Bellen team turned to fruit flies. The first surprising discovery made by the lead author, Hyunglok Chung, was that the ACOX1 protein is abundant and critical for the maintenance of glia, cells that support neurons. This uncovered a previously unknown role of peroxisomes in glial cells and paved the way for further experiments.

To understand how ACOX1 variants affect the function of glia, they generated two mutant fly lines, the first one lacked both the copies of ACOX1 gene and the second, carried the substitution mutation (N237S) found in one of the ACOX1 genes in the Mitchell Syndrome patients.

“Flies lacking ACOX1 mimicked the symptoms of ACOX1 deficiency in humans, including elevated levels of very-long-chain-fatty acids along with dramatic loss of glia and neurons and progressively impaired neuronal function. When we reduced the synthesis of very-long-chain-fatty acids in these flies by administering the drug bezafibrate, we observed significant improvement in lifespan, vision, motor coordination and neuronal function, implicating elevated levels of these lipids and their excessive accumulation in glia as an important contributor,” said Chung, postdoctoral fellow in the Bellen lab.

It is remarkable how well bezafibrate suppressed the symptoms of ACOX1 deficiency, suggesting a new therapeutic avenue for patients with this condition,” Bellen said.

In contrast to the loss of ACOX1, the introduction of the single amino acid substitution (N237S) in ACOX1 gene resulted in a hyperactive ACOX1 protein. Typically, breakdown of very-long-chain-fatty acids by the enzymatic action of ACOX1 produces small amounts of highly reactive oxygen species, but glial cells quickly neutralize them. However, in Mitchell’s Syndrome, hyperactive ACOX1 produces copious amounts of toxic reactive oxygen species, leading to the destruction of glia and their neighboring neurons.

The harmful effects due to hyperactive ACOX1 were potently reversed with the antioxidant N-acetyl cysteine amide (NACA). However, NACA did not suppress the lethality or toxic effects in flies that lacked ACOX1, a clear indication that the two diseases act via entirely different pathways and would need to be treated with two distinct therapeutic strategies.

“This study is a prime example of how combining UDN’s unique team science approach with power of fruit fly genetics is facilitating rapid and phenomenal progress in rare diseases research. We take on cases of patients with conditions never described before, uncover new diseases and find definitive molecular diagnosis for them. We make significant progress in unraveling the causes of these novel diseases and rapidly identify and test promising new treatment options,” Bellen said. “We have successfully identified more than 25 disease-causing genes within the past three years – a task that typically takes many years.”

The study appears in the journal Neuron.

https://www.texaschildrens.org/content/news-release/solving-puzzle-mitchell-syndrome

Chung HL, Wangler MF, Marcogliese PC, Jo J, Ravenscroft TA, Zuo Z, Duraine L, Sadeghzadeh S, Li-Kroeger D, Schmidt RE, Pestronk A, Rosenfeld JA, Burrage L, Herndon MJ, Chen S; Members of Undiagnosed Diseases Network; Shillington A, Vawter-Lee M, Hopkin R, Rodriguez-Smith J, Henrickson M, Lee B, Moser AB, Jones RO, Watkins P, Yoo T, Mar S, Choi M, Bucelli RC, Yamamoto S, Lee HK, Prada CE, Chae JH, Vogel TP, Bellen HJ. Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms. Neuron. 2020 May 20;106(4):589-606.e6. doi: 10.1016/j.neuron.2020.02.021. Epub 2020 Mar 12. PMID: 32169171; PMCID: PMC7289150.

Abstract

ACOX1 (acyl-CoA oxidase 1) encodes the first and rate-limiting enzyme of the very-long-chain fatty acid (VLCFA) β-oxidation pathway in peroxisomes and leads to H2O2 production. Unexpectedly, Drosophila (d) ACOX1 is mostly expressed and required in glia, and loss of ACOX1 leads to developmental delay, pupal death, reduced lifespan, impaired synaptic transmission, and glial and axonal loss. Patients who carry a previously unidentified, de novo, dominant variant in ACOX1 (p.N237S) also exhibit glial loss. However, this mutation causes increased levels of ACOX1 protein and function resulting in elevated levels of reactive oxygen species in glia in flies and murine Schwann cells. ACOX1 (p.N237S) patients exhibit a severe loss of Schwann cells and neurons. However, treatment of flies and primary Schwann cells with an antioxidant suppressed the p.N237S-induced neurodegeneration. In summary, both loss and gain of ACOX1 lead to glial and neuronal loss, but different mechanisms are at play and require different treatments.

Jafarpour S, Khoshnood M, Santoro JD. Child Neurology: Neurodegenerative Encephalomyelopathy Associated With ACOX1 Gain-of-Function Variation Partially Responsive to Immunotherapy. Neurology. 2022 Aug 23;99(8):341-346. doi: 10.1212/WNL.0000000000200935. Epub 2022 Jun 17. PMID: 35715200.

Abstract

Acyl-CoA oxidase 1 (ACOX1) is a peroxisomal enzyme involved in beta-oxidation of very-long-chain fatty acids. Although loss of function of ACOX1 had been previously described, gain-of-function variation of ACOX1 gene has been only recently identified, with a paucity of known cases. Gain-of-function variation results in overproduction of reactive oxygen species, resulting in progressive neurodegeneration with discrete relapses. We report the case of a 19-year-old woman with a 5-year history of longitudinally extensive posterior predominant myelopathy, bilateral corneal scars, and white matter lesions who presented with first-time seizure, progressive sensorineural hearing loss, ichthyosiform rash, and cauda equina syndrome. Extensive workup was unrevealing. The patient showed no response to high-dose steroids but stabilization and improvement with return to baseline over 6 months with IVIg and low-dose mycophenolate mofetil. Whole-exome sequencing performed 4 years before was nondiagnostic, but subsequent reanalysis revealed a heterozygous variation in the ACOX1 gene (NM_004035.6: c.710A>G, p.Asn237Ser), now considered to be pathogenic. This case reports a rare condition and highlights the importance of reanalysis of previously nondiagnostic genome/exome sequencing data. Furthermore, the patient's clinical stability for over 1 year on immunotherapy raises the possibility of disease modification in an otherwise universally fatal condition.

Shen M, Chen Q, Gao Y, Yan H, Feng S, Ji X, Zhang X. A de novo heterozygous variant in ACOX1 gene cause Mitchell syndrome: the first case in China and literature review. BMC Med Genomics. 2023 Jul 3;16(1):156. doi: 10.1186/s12920-023-01577-w. PMID: 37400800; PMCID: PMC10318832.

Abstract

Background

Mitchell syndrome (MITCH) is a rare autosomal dominant hereditary disorder, characterized by episodic demyelination, sensorimotor polyneuropathy and hearing loss. MITCH is caused by heterozygous mutation in the ACOX1 gene, which encodes straight-chain acyl-CoA oxidase, on chromosome 17q25.1. Only 5 unrelated patients have been reported so far, and no reports from China. Here, we describe the first MITCH case in a Chinese individual.

See: https://childnervoussystem.blogspot.com/2021/02/acox1-gain-of-function-mutation.html



Tuesday, September 8, 2026

Primary amoebic meningoencephalitis 7

A North Carolina teenager has died from a rare and often fatal infection caused by an amoeba found in warm freshwater, state health officials said.

In a GoFundMe set up by the teen’s mother, she shared that his first symptom was "severe headaches."

"I never imagined that something like this could be so serious," she said.

The illness is caused by Naegleria fowleri, an amoeba (one-celled living organism) that inhabits ponds, lakes and rivers.

"We extend our condolences to the family, friends and community impacted by this loss," the North Carolina Department of Health and Human Services said in a statement obtained by news outlets.

The teen’s death was reported just days after an 8-year-old girl in Louisiana succumbed to the infection.

"While these infections are very rare, this is an important reminder that this amoeba is present in our state and across the U.S.," State Epidemiologist Zack Moore, M.D., said in a prior statement. "There are steps people can take to reduce their risk of infection while swimming during the warmer months."

Naegleria fowleri — commonly referred to as a "brain-eating amoeba" — causes a life-threatening brain infection called primary amebic meningoencephalitis (PAM).

The amoeba is most active in the months that the water temperature stays elevated.

"It's typically this time of year when it's very hot outside, when there hasn't been a lot of rain … and the lakes and ponds get pretty stagnant and get very warm, and that's a great breeding ground for these type of natural inhabitants of those waters," Dr. Jeffrey Kahn, chief of pediatric infectious diseases at UT Southwestern and Children's Health in Dallas, Texas, told Fox News Digital.

The infection can occur when water containing the amoeba is forced up the nose, allowing the amoeba to travel to the brain. This can occur when someone jumps or dives into the water or participates in water sports.

"Once that happens, it's nearly a lethal disease," Kahn warned. "The mortality rate is close to 100%."

Naegleria fowleri does not cause illness via swallowing.

Warning signs to recognize

The initial symptoms of PAM usually begin about five days after exposure, but they can be noticed sooner.

Early signs usually include headache, nausea, fever and/or vomiting, the CDC’s website states.

As the infection progresses, people may experience confusion, slurred speech, stiff neck, disorientation, hallucinations, seizures and coma.

"By the time the [amoeba] enters the brain and starts to basically erode the brain tissue, it's too late."

"The initial symptoms are actually quite nonspecific — they don't point to one disease or another — but they can progress very rapidly," Kahn noted.

Diagnosis involves testing cerebrospinal fluid obtained through a spinal tap; specialized laboratory testing may be needed.

Symptoms usually begin about five days after exposure, although they can appear anywhere from one to 12 days later. Once symptoms start, the disease progresses rapidly.

Most people die within one to 18 days after symptoms begin, typically around five days, per the CDC.

Prevention of infection

To prevent potentially fatal infections, Kahn recommends either avoiding the types of waters where the amoeba is likelier to be found, or taking added precautions.

"If you are swimming in those waters, wear a nose clip, don't put your head underwater, those types of things," he said.

Drinking contaminated water does not present a risk, and the infection does not spread from one person to another.

Because the amoeba is found in soil, the CDC also recommends avoiding stirring up the sediment at the bottom of lakes, ponds and rivers.

Treatment of brain-eating amoebas

When a patient has been diagnosed with a brain-eating amoeba, treatment involves a combination of antimicrobial and anti-amoebic medications, including amphotericin B, azithromycin, rifampin and miltefosine.

"There has been a cocktail of antibiotics and antimicrobials that have been tried over the years — but with a very, very small number of cases every year, it's tough to draw any conclusions from that," Kahn said.

"In the cases we've seen, we typically throw a lot of these antibiotics as a therapeutic modality, but by the time the [amoeba] enters the brain and starts to basically erode the brain tissue, it's too late."

Those who experience sudden headache, fever, stiff neck or vomiting — especially if they have recently been swimming in warm freshwater — should seek immediate medical attention, the CDC recommends.

Melissa Rudy

https://www.foxnews.com/health/teen-dies-brain-eating-amoeba-days-after-young-girl-succumbs-same-rare-infection

Sunday, September 6, 2026

Unattended children again

Virginia mom speaks out after being put on child abuse registry for letting child walk alone

A Virginia mom is appealing a criminal charge and her placement on the state’s child abuse and neglect registry after her 5-year-old son was stopped by security while walking alone through their gated community.

Karyann Parkinson said her son, Sam, had been walking along a familiar neighborhood path past a pond to collect goose feathers when a security guard encountered him and brought him home.

Police and Child Protective Services became involved, and Parkinson, who was eight months pregnant at the time, had her six-month jail sentence suspended, but the charge remains.

She was convicted of contributing to the delinquency of a minor, a first-degree misdemeanor, and was also placed on Virginia's Child Abuse and Neglect Central Registry for seven years.

Parkinson said she understands the shock people feel hearing about a child alone near a body of water, but sought to clarify what happened that day.

"I didn't send him to play at the pond," she told "Fox & Friends Weekend." "I sent him down the path that happens to go past the pond to collect goose feathers... I know that a lot of people have seen the headlines and seen '5-year-old alone at a pond.' And I think if I saw that in isolation, I'd probably be alarmed, too."

"But what this was, was a 5-year-old on a pathway that he's very familiar with in his neighborhood that he loves, the only place that he can remember ever living. And it just got turned into this whole situation where a lot of people were suddenly intervening and feeling like this was a really drastic parenting choice," she said.

The most difficult part for Parkinson is being on the Child Protective Services registry for so long, she told Fox News. That means she won't be able to volunteer in Sam's classroom until he enters sixth grade.

"We need to stop parenting from a place of fear and a place, you know, of obsessing over the unknown or some boogeyman who's going to jump out from behind a bush," Parkinson said.

She said her son was "pretty shaken up" after the incident but has since recovered.

"We had to do a lot of reassuring him and telling him, 'You didn't do anything wrong,'" Parkinson said. "He would ask me, 'Mom, am I allowed to ride my bike to swim practice? Am I allowed to ride my back to the tennis courts?'"

"Now it's just a blip on his radar. It's not really a part of his life anymore," she added.

Max Bacall

https://www.foxnews.com/media/virginia-mom-placed-child-abuse-registry-7-years-letting-5-year-old-walk-alone

See: https://childnervoussystem.blogspot.com/2015/04/unattended-children.html

https://childnervoussystem.blogspot.com/2016/02/unattended-children-2.html

https://childnervoussystem.blogspot.com/2024/11/unattended-children-redux.html



Wednesday, September 2, 2026

Sulforaphane and autism

McGuinness G, Kim Y. Sulforaphane treatment for autism spectrum disorder: A systematic review. EXCLI J. 2020 Jun 26;19:892-903. doi: 10.17179/excli2020-2487. PMID: 33013262; PMCID: PMC7527484.

Abstract

Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental condition characterized by social communication impairment, delayed development, social function deficit, and repetitive behaviors. The Center for Disease Control reports an increase in ASD diagnosis rates every year. This systematic review evaluated the use of sulforaphane (SFN) therapy as a potential treatment option for individuals with ASD. PubMed.gov, PubMed Central, Natural Medicines, BoardVitals, Google Scholar and Medline were searched for studies measuring the effects of SFN on behavior and cognitive function. All five clinical trials included in this systematic review showed a significant positive correlation between SFN use and ASD behavior and cognitive function. The current evidence shows with minimal side effects observed, SFN appears to be a safe and effective treatment option for treating ASD.

Zhang X, He Q, Zhu YY, Lorimer GH, Bayram H, Ghiladi RA, Wang J. Emerging Promise of Sulforaphane in Autism: A Comprehensive Review of Its Therapeutic Potential and Mechanisms. ACS Chem Neurosci. 2026 Aug 5;17(15):2880-2892. doi: 10.1021/acschemneuro.6c00282. PMID: 42473985.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that emerges in early childhood and significantly impacts the quality of life for individuals and families. Currently, there are no specific medications available for ASD. Increasing attention is now focused on bioactive compounds with anti-inflammatory and antioxidant properties. Sulforaphane (SFN), a key member of the isothiocyanate family, is abundant in cruciferous vegetables. It exhibits potent antioxidant and anti-inflammatory effects with minimal side effects, while oxidative stress and inflammation are recognized triggers in ASD pathogenesis. As research deepens, SFN's physiological activities─including antioxidant, neuroprotective, and anti-inflammatory properties are gaining heightened attention. Building on prior studies, this review comprehensively summarizes seven potential pathways through which SFN protects neurodevelopment or reverses ASD-related neural damage, including Keap1/Nrf2/ARE; MAPKs; NF-κB; HSR; AhR/CYP1; Sirtuin-FOXO; and mTOR/autophagy signaling pathways, elucidating the potential mechanisms underlying its multifaceted actions. This review offers new insights for the comprehensive utilization of sulforaphane and the treatment of ASD.

Long J, Liao X, Tang Z, Han K, Chen J, Wang X, Liu J, Zhang Y, Zhang H. Investigating the clinical efficacy, safety and molecular mechanism of sulforaphane in autism spectrum disorder: an integrated study combining meta-analysis, network pharmacology, and computational biology. BMC Pharmacol Toxicol. 2025 Nov 22;26(1):217. doi: 10.1186/s40360-025-01052-5. PMID: 41275316; PMCID: PMC12751817.

Abstract

Background: Sulforaphane, a natural antioxidant rich in cruciferous vegetables, has emerged as a promising dietary supplement for autism spectrum disorder (ASD). However, its therapeutic efficacy remains controversial, and the pharmacological mechanisms are not fully elucidated.

Methods: Eligible randomized controlled trials were retrieved from PubMed, Web of Science, Embase, and Cochrane Library databases. Review Manager 5.4 was used for meta-analysis and bias risk assessment. Network pharmacology, Mendelian randomization, GEO data analyses, molecular docking, and molecular dynamics simulation were employed to explore the mechanisms of sulforaphane in ASD.

Results: Six trials involving 333 participants were included in the meta-analysis. Pooled results demonstrated that both 4-5 weeks and 8-10 weeks of sulforaphane supplementation significantly decreased the scores on the Social Responsiveness Scale compared to placebo controls. No significant difference was observed in the incidence of adverse events. Network pharmacology identified 10 core targets of sulforaphane in ASD, including AKT1, EGFR, HSP90AA1, SRC, CASP3, STAT1, MAPK1, MMP9, MAPK8, and JAK2. These targets were implicated in the PI3K-Akt signaling pathway, MAPK signaling pathway, Chemokine signaling pathway, Chemical carcinogenesis - reactive oxygen species, TNF signaling pathway, Th17 cell differentiation, mTOR signaling pathway, and IL-17 signaling pathway. Mendelian randomization further revealed an inverse association between STAT1 levels and ASD risk. GEO transcriptomic data provided independent validation for the network pharmacology predictions. The binding energies between sulforaphane and the top 10 core targets are all ≤ -4.0 kcal/mol. Molecular dynamics simulations further validated the stable interaction between MMP-9 and sulforaphane.

Conclusion: Sulforaphane may serve as an efficacious and safe adjunctive therapy for ASD, mediated by its anti-oxidant and anti-inflammatory effects along with the modulation of autophagy.

Guo J, Wang Y, He W, Lou M, Peng Y, Shi H, Lian A. Effects of sulforaphane on ABC and SRS scales in patients with autism spectrum disorder: a meta-analysis. Brain Dev. 2025 Apr;47(2):104321. doi: 10.1016/j.braindev.2025.104321. Epub 2025 Feb 14. PMID: 39951914.

Abstract

Autism spectrum disorder (ASD) has become an increasingly prominent global health issue. Sulforaphane is a phytochemical with multiple functions that target many of the same biochemical and molecular pathways (biomarkers) associated with ASD. This study aimed to conduct a meta-analysis based on sulforaphane's effect on Aberrant Behavior Checklist (ABC) and Social Responsiveness Scale (SRS) in patients with ASD. We conducted comprehensive searches in the PubMed, Medline, Cochrane, EMBASE, and Web of Science databases from their inception. The modified Cochrane risk of bias tool was used to check the risk of bias of the included studies. Review Manager 5.3 software was used to conduct this meta-analysis. The results of this meta-analysis showed that sulforaphane significantly improved irritability and hyperactivity symptoms, suggesting that sulforaphane has the potential for the combined treatment of autism. Additional studies are needed to confirm and explore the effect of sulforaphane.

Ou J, Smith RC, Tobe RH, Lin J, Arriaza J, Fahey JW, Liu R, Zeng Y, Liu Y, Huang L, Shen Y, Li Y, Cheng D, Cornblatt B, Davis JM, Zhao J, Wu R, Jin H. Efficacy of Sulforaphane in Treatment of Children with Autism Spectrum Disorder: A Randomized Double-Blind Placebo-Controlled Multi-center Trial. J Autism Dev Disord. 2024 Feb;54(2):628-641. doi: 10.1007/s10803-022-05784-9. Epub 2022 Nov 24. PMID: 36427174.

Abstract

Sulforaphane has been reported to possibly improve core symptoms associated with autism spectrum disorders from mostly small size studies. Here we present results of a larger randomized clinical trial (N = 108) in China. There were no significant changes in caregiver rated scales between sulforaphane and placebo groups. However, clinician rated scales showed a significant improvement in the sulforaphane group, and one third of participants showed at least a 30% decrease in score by 12 weeks treatment. The effects of sulforaphane were seen across the full range of intelligence and greater in participants over 10 years. Sulforaphane was safe and well-tolerated even for young children. The inconsistent results between caregiver and clinician rated scales suggest more clinical trials are needed to confirm our findings.