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Remove items from your saved list<\/a> to add more.<\/p>\n AAA<\/p>\n In family videos, Sasha Lipworth beams, open-mouthed and elated as she zooms past on her aquamarine scooter. She giggles as she ambles along a footpath hand-in-hand with her pint-sized friend, and trills \u201cI\u2019m calling mummy\u201d as she presses a comically large telephone receiver to her tiny ear.<\/p>\n There\u2019s footage of Sasha sitting on her father\u2019s lap, and singing Happy Birthday before blowing out the four candles on her cake.<\/p>\n Within a few months, an unknown quirk in Sasha\u2019s genetic coding would begin to rob her of the ability to speak, hold a spoon, use a toilet or play with the most basic of baby toys.<\/p>\n By the time Sasha was 4\u00bd, her ultra-rare disorder had robbed her of every skill she had developed since infancy. She was having hundreds of epileptic seizures each day.<\/p>\n Now nine, Sasha has been nonverbal longer than she was able to speak. For her past five birthdays, she couldn\u2019t blow out a single candle.<\/p>\n Related Article \u201cThat is crazy when you express it like that,\u201d Sasha\u2019s father, David Lipworth, says. \u201cIt\u2019s taking too long to get this done.\u201d<\/p>\n David and Sasha\u2019s mother, Nadine Lipworth, have devoted their lives to Sasha \u2013 who needs 24-hour care \u2013 and to finding a way to restore her abilities and give her the chance to gain new skills.<\/p>\n \u201cWe were told that there was no treatment and no cure. That wasn\u2019t going to be an option,\u201d Nadine says. \u201cWe knew Sasha before she lost everything, and we wanted to give her her future back.\u201d<\/p>\n With no financial backing from any institution, the Lipworths have assembled a crack team of scientists from Australia and the United States to undertake the painstaking work of developing a Sasha-specific genetic therapy.<\/p>\n They are months away from confirming that they have got it: bespoke gene patches called Antisense Oligonucleotides (ASO), the latest frontier in experimental precision therapies for rare genetic disorders that were, until recently, considered \u201cundruggable\u201d.<\/p>\n Mini lab-grown Sasha brains are key to the final stages of testing three potential treatment candidates. The team then plans to send the best performer to the US for mandatory safety testing. If all goes well, Sasha could receive her first dose by her 10th birthday, in March.<\/p>\n \u201cTo be so close to the finish line is amazing,\u201d David says. \u201cThis disease has stolen so much from her, but that spark she has had since she was a baby gives us hope that we can get her back.\u201d<\/p>\n Among the regulatory, logistical and clinical obstacles sits a $1 million hurdle: securing philanthropic donations to cover the cost of toxicology testing in a US laboratory, then, hopefully, manufacturing a new medicine.<\/p>\n If the Lipworths succeed, they hope to blaze a trail for other children whose rare genetic diseases could be treated with RNA-targeting precision medicines.<\/p>\n \u201cI cannot leave this world until my daughter can tell someone if she is in pain or being harmed,\u201d Nadine says.<\/p>\n Nadine and David Lipworth quit their jobs to care for Sasha and support their mission. David has become a citizen scientist in RNA therapeutics, impressing with his nous internationally renowned molecular biologist and antisense pioneer Professor Emerita Sue Fletcher.<\/p>\n Nadine is spearheading crucial fundraising for the expensive endeavour through a GoFundMe page, raffles and tax-deductible donations via the Epilepsy Foundation<\/a>.<\/p>\n \u201cIt has all been up to us,\u201d Nadine says.<\/p>\n Cut-and-paste<\/p>\n In March 2024, the University of Sydney\u2019s RNA for Rare Diseases team identified a spontaneous mutation in Sasha\u2019s SLC6A1 gene<\/a>, which encodes a protein called GAT-1 that recycles the brain\u2019s main calming neurotransmitter, affecting how messages move through the brain. Only one other person in the world is known to have this variant.<\/p>\n In every human cell, there are more than 3 billion base pairs of DNA, each pair a combination of the letters A, T, C and G.<\/p>\n \u201cIn Sasha\u2019s case, just one letter has been changed, and this is causing her disorder,\u201d Fletcher says.<\/p>\n Related Article The single-letter change does not alter the protein code in Sasha\u2019s DNA. It alters how the code is edited, cut and pasted together.<\/p>\n When a cell needs to make a protein, it copies the gene containing that protein\u2019s assembly instructions from the master blueprint, DNA, to make a temporary, portable transcription called messenger RNA (mRNA). This transcription needs to be edited before it reaches the cell\u2019s protein-building factory.<\/p>\n The initial unedited message (pre-mRNA) is made up of exons \u2013 sequences of the protein-making code \u2013 which are separated by non-coding filler sequences called introns. This is where Sasha\u2019s mutation wreaks havoc.<\/p>\n The cell\u2019s machinery \u2013 cellular scissors and glue \u2013 needs to \u201csplice out\u201d the non-coding introns and paste the exon coding sequences together.<\/p>\n Sasha\u2019s single-letter change signals the cellular scissors to splice in the middle of an exon, severing crucial information, rendering it impossible to correctly assemble the protein from the incorrectly edited instructions.<\/p>\n \u201cEverything downstream [from the errant splice] is garbled,\u201d Fletcher says.<\/p>\n If Sasha\u2019s splicing error was a TV murder mystery<\/p>\n Think of mRNA as a whodunit on commercial television, where the exons are the movie and the introns the ad breaks.<\/p>\n To watch the movie without ad breaks, you need to edit out the introns and stitch the exon sequences together.<\/p>\n Sasha\u2019s movie is being spliced in the middle of an exon at the climactic plot twist – excising the moment that the true murderer is unmasked, and their fiendish motive revealed – rendering the rest of the movie incomprehensible.<\/p>\n \u201cIf we can overcome that one small glitch, Sasha\u2019s cells will make a perfectly normal protein from the gene that carries this one damaging \u2018letter\u2019 change,\u201d Fletcher says.<\/p>\n To fix the glitch, Sasha\u2019s research teams turned to ASOs: short, synthetic strands of RNA modified with such precision that they can bind to a specific mRNA sequence.<\/p>\n Related Article In a laboratory at the Queensland University of Technology, Dr Laura Croft has been tending to dishes of miniature Sasha brains. For 140 days, Croft has raised them on a steady diet of nutrient-rich media.<\/p>\n These brain organoids \u2013 3D brain tissue derived from Sasha\u2019s blood cells reprogrammed into stem cells \u2013 are a critical component to testing treatment candidates designed with painstaking specificity for Sasha and her ultra-rare mutation.<\/p>\n \u201cIt\u2019s so emotional seeing them,\u201d Nadine says after a recent visit to Croft\u2019s lab and seeing her daughter\u2019s mini brains. \u201cI feel like crying now thinking about it.\u201d<\/p>\n Croft specialises in advancing rare disease therapies for \u201cn-of-1\u201d cases, like Sasha: a patient whose condition is so rare that she represents the entire patient cohort.<\/p>\n \u201cIt is so exciting,\u201d Croft says. \u201cIt\u2019s possible that Sasha will be the first child in Australia to be treated with an Australian-developed n-of-1 ASO.\u201d<\/p>\n Croft screened about 20 ASOs engineered by her team, Fletcher and US researchers. David thinks of them as masking tape that covers the errant splice site, shielding it from the cellular scissors.<\/p>\n<\/p>\n \u201cASOs are the ultimate precision medicines<\/a>,\u201d Fletcher says. \u201cThey can be targeted very specifically to certain types of gene mutations.\u201d<\/p>\n But not every genetic disorder could be targeted by this bespoke approach. \u201cIt very much depends on the gene and the specific mutation,\u201d Fletcher says.<\/p>\n The ASO Nusinersen was the first-ever disease-modifying treatment for spinal muscular atrophy<\/a> \u2013 the biggest genetic killer of children under two years of age<\/a>.<\/p>\n The world\u2019s first person to be treated with an ASO made just for them was a seven-year-old girl named Mila Makovec at Boston Children\u2019s Hospital in 2018 \u2013 within a year of her diagnosis. Tragically, Mila, who had the rare and fatal neurodegenerative disorder Batten disease, died in 2021. But her experimental drug, dubbed Milasen<\/a>, was shown to reduce her seizures and provided a blueprint for the rapid development of highly customised therapeutics.<\/p>\n An estimated 15 to 30 per cent of all genetic diseases<\/a> are caused by mutations affecting RNA splicing, suggesting they may be amenable to ASOs, Croft says.<\/p>\n In Croft\u2019s lab, three ASOs corrected the errant splicing at the RNA level in Sasha\u2019s lab-made brain cells.<\/p>\n \u201cWe have to repeat these studies at least three or four times for all three ASOs,\u201d says Croft, a task she expects to take three months.<\/p>\n \u201c[Then] we need to make sure that this translates into functional protein, [and] which one is the best at restoring the GAT-1 protein function in Sasha\u2019s cells,\u201d she adds.<\/p>\n Preliminary evidence shows at least one ASO does just that, Croft says. It will cost $75,000 to confirm a top candidate.<\/p>\n Simultaneously, Sasha\u2019s team have been working to select a laboratory to conduct toxicology testing as soon as a lead candidate is identified. This, plus manufacturing a clinical-grade drug, will cost $900,000, which is why the Lipworths\u2019 focus is now on finding new philanthropic donors, fast.<\/p>\n \u201cWe are progressing the program as quickly as possible because we know that the earlier the intervention occurs, the better the outcome for Sasha is likely to be,\u201d Croft says.<\/p>\n The Lipworths hope to have Sasha treated at the Sydney Children\u2019s Hospital Network (SCHN).<\/p>\n A network spokesperson said that administering experimental therapy is governed by rigorous ethical, regulatory and legal requirements, and that the network was developing pathways that enable children with rare diseases to access highly personalised therapies.<\/p>\n Related Article Sasha\u2019s parents dream of Sasha regaining all the skills she has lost and more, attending a mainstream school and, in adulthood, having a productive, fulfilling job.<\/p>\n A trial of an experimental ASO to treat Dravet syndrome<\/a> \u2013 a neurodevelopmental disorder triggered similarly to Sasha\u2019s \u2013 found that children regained skills they had lost and developed some new abilities, including communication, language and gross and fine motor skills.<\/p>\n \u201cIf we can get Sasha treated soon, while her brain is still developing, then who knows what the future holds for her,\u201d David says.<\/p>\n Professor Zornitza Stark, clinical geneticist<\/a> at Murdoch Children\u2019s Research Institute, says: \u201cThe explosion in precision treatments over the last 10 years has been hugely exciting.\u201d<\/p>\n Stark says that even when an ASO is developed for a single child, the principles learnt can help advance the entire field of new-generation therapies.<\/p>\n One day, David hopes this will be as routine as surgery: \u201cYou go to the doctor, the doctor finds your mutation and develops a personalised genetic treatment that targets [it].\u201d<\/p>\n But infrastructure must be built for these personalised therapies to be developed faster and more cheaply.<\/p>\n There is no doubt, Fletcher says, that Sasha is at the forefront of her parents\u2019 minds. \u201cBut they have been very clear that … whatever the outcome for Sasha, we are working on a pipeline and creating opportunities to help the next child, and the next and the next.\u201d<\/p>\n \u201cWe must get this done,\u201d Nadine says. \u201cThe impact is bigger than one child.\u201d<\/p>\n Start the day with a summary of the day\u2019s most important and interesting stories, analysis and insights. Sign up for our Morning Edition newsletter<\/a>.<\/p>\n Save<\/p>\n You have reached your maximum number of saved items.<\/p>\n![\"Sasha](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2026\/07\/7303ba5fa684576ae0ec2707ce6f01a3baf204c0.jpeg\")
Sasha with her parents, Nadine and David Lipworth.Wolter Peeters<\/p>\n![\"Keira](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2026\/06\/1782615927_519_20e3ac10959579193db4a9baef041a117894e23c.jpeg\")
<\/a><\/p>\n![\"Sasha](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2026\/07\/0a3f8fc22edb8d2b881f0f06dbdfe0ffc0453688.jpeg\")
Sasha with her father, David Lipworth.Wolter Peeters\u2018It\u2019s up to us\u2019<\/p>\n![\"Bethan](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2026\/07\/f44f811856952a0f4bd067ccbb5bc73e46d345d2.jpeg\")
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<\/a>The genetic masking tape<\/p>\n![\"Dr](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2026\/07\/85afd68b612c5aeecafdf583ab46806af7576b081a13ab634d2e28e6218de70b.jpeg\")
Dr Laura Croft and Nadine Lipworth with Sasha\u2019s brain organoids.David Lipworth<\/p>\n![\"Nadine](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2026\/07\/8fc4b3e3ecd052efb7321c633c462f75932abfd1b441f2e19051df7f4d24b098.jpeg\")
Nadine said she can\u2019t leave this world until her daughter can communicate if she is in pain.Nadine Lipworth<\/p>\n![\"Kate](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2026\/07\/5883f83bcf9db9503a91a0a5f1a084c85317068e.jpeg\")
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