Doctors placed a stent in the heart of a fetus still inside the womb diagnosed with a rare and severe heart defect

Amazing stuff!

"Lauren and Alex Klingsporn were shocked by the news that their unborn son, Brooks, would need a series of surgeries after he was born to fix a rare and severe heart defect.

Brooks’ situation became even more desperate when doctors learned of another problem that was causing lung damage, making it unlikely he’d be healthy enough for the surgeries after birth. Babies born with Brooks’ condition have almost no chance of survival.

So, Texas Children’s Hospital tried something that sounds like science fiction. Doctors placed a stent in Brooks’ heart while he was still in the womb, a complex, high-risk procedure the hospital has performed only about 30 times over the past decade. ..."

"... Fetal cardiac intervention is complex surgery that is performed in the hospital. The mother and fetus are sedated, and an incision is made in the mother’s abdomen, similar to that for a cesarean section. An incision is made in her uterus, exposing the fetus. Guided by ultrasound images, a specialized needle is inserted into the heart of the fetus. A tiny tube, or catheter, with a balloon attached to it is introduced into the heart. The balloon is inflated to expand the valve and allow blood to flow. After the procedure, the fetus is returned to the mother’s uterus. Amniotic fluid is replaced, and the uterus and abdomen are closed. ..."

Texas Children's novel, in-utero surgery saved baby with rare defect

Fetal Cardiac Intervention

Gene-therapy breakthrough allows congenitally deaf children to hear and respond to speech in China

Good news! "may yield other treatments for more of the 30 million kids with genetic hearing loss"

"A novel gene therapy approach has given five children who were born deaf the ability to hear. The method, which overcomes a roadblock presented by large genes, may be useful in other treatments, according to researchers. ...

treated six children aged 1 to 7 who were suffering from an inherited mutation of the OTOF gene, which manufactures a protein important in transmitting signals from the ear to the brain.

Five of the six children showed improvement in hearing over the 26-week trial, with four outcomes described by researchers as “robust.” ...

The three older children, with cochlear implants turned off, could understand and respond to speech by 26 weeks, with two able to recognize speech in a noisy room and have a telephone conversation. ...

Before the trial began, researchers had to tackle a significant technical problem related to the size of the OTOF gene. The procedure called for the gene to be inserted into the cochlea using a type of virus researchers commonly use for this purpose.

The virus inserts the gene into the DNA of target cells, which then begin to manufacture the missing protein. The problem in this case is that the OTOF gene is too big for the virus to hold. Researchers got past this by dividing the gene into two, encapsulating the halves into separate viruses, and then injecting a mixture with both halves of the gene into the cochlea. ..."

"... the researchers found the novel gene therapy to be an effective treatment for patients with a specific form of autosomal recessive deafness caused by mutations of the OTOF (otoferlin) gene, called DFNB9. With its first patient treated in December 2022, this research represents the first human clinical trial to administer gene therapy for treating this condition ..."

From the abstract:

"Background

Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.

Methods

This single-arm, single-centre trial enrolled children (aged 1–18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing.

Findings

Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1–2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40–57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5–4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery.

Interpretation

AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. ..."

Gene-therapy breakthrough allows congenitally deaf children to hear — Harvard Gazette Harvard scientist co-leads research, which targeted specific condition, may yield other treatments for more of the 30 million kids with genetic hearing loss

Gene Therapy Restores Hearing in Children with Hereditary Deafness

AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial (no public access)

New nanoparticles can perform gene editing in the lungs

Good news! After liver and muscles, the lungs are next!

"Engineers ... have designed a new type of nanoparticle that can be administered to the lungs, where it can deliver messenger RNA encoding useful proteins.

With further development, these particles could offer an inhalable treatment for cystic fibrosis and other diseases of the lung, the researchers say. ...

In a study of mice, Anderson and his colleagues used the particles to deliver mRNA encoding the machinery needed for CRISPR/Cas9 gene editing. That could open the door to designing therapeutic nanoparticles that can snip out and replace disease-causing genes. ...
Messenger RNA holds great potential as a therapeutic for treating a variety of diseases caused by faulty genes. One obstacle to its deployment thus far has been difficulty in delivering it to the right part of the body, without off-target effects. ..."

"The ability to create in vivo genomic medicines for tissues other than the liver has been impeded by difficulties in delivery. Using a high-throughput platform, we developed lipid nanoparticles that can effectively deliver mRNA and CRISPR–Cas9 gene editing tools to the lungs through intratracheal administration, expanding the potential clinical uses of gene editing and mRNA-based technologies."

From the abstract:

"The expanding applications of nonviral genomic medicines in the lung remain restricted by delivery challenges. Here, leveraging a high-throughput platform, we synthesize and screen a combinatorial library of biodegradable ionizable lipids to build inhalable delivery vehicles for messenger RNA and CRISPR–Cas9 gene editors. Lead lipid nanoparticles are amenable for repeated intratracheal dosing and could achieve efficient gene editing in lung epithelium, providing avenues for gene therapy of congenital lung diseases."

New nanoparticles can perform gene editing in the lungs | MIT News | Massachusetts Institute of Technology Using these RNA-delivery particles, researchers hope to develop new treatments for cystic fibrosis and other lung diseases.

Lipid nanoparticle-enabled gene editing in the lung via inhalation

Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing (no public access)