Timeline: ~20 Weeks
Cost: ~$89,900
The SPATA Foundation has formed a partnership with Unravel Biosciences, a bioscience company dedicated to developing new therapeutics for complex disorders.
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Unravel has multiple drugs in clinical trials, and has already found 4 drug targets for other rare/complex diseases.
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Our partnership with Unravel is the first research partnership dedicated to researching a treatment for SPATA5 and SPATA5L1!
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We're very excited for this opportunity, and encourage you to learn more about this project below.
Drug Repurposing with Unravel Biosciences
START: TBA
ESTIMATED END: TBA
What is Drug Repurposing?
Drug Repurposing (also known as drug repositioning) is a process of identifying new therapeutic use(s) for old/existing/available drugs. Over the years, researchers have found drugs that were created to treat one thing work for something else. For example: Topiramate was originally create as an epilepsy treatment. It’s still used as an epilepsy treatment, but they also found it can be used to treat certain types of obesity. So, Topiramate was repurposed and is also now used for obesity treatment.
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Drug Repurposing is now being applied to rare diseases. There are a handful of companies in the US doing drug repurposing research specifically for rare diseases.
Does it Work?
Yes! There are lots of Rare Disease foundations, just like The SPATA Foundation, utilizing drug repurposing. Check out Maggie's Pearl, who have utilized drug repurposing to identify a treatment for an ultra-rare condition called Congenital Disorder of Glycosylation Type 1A. They are currently in a Phase III Clinical Trial.
Unravel Biosciences harnessed patient RNA data to uncover a promising breakthrough for Rett Syndrome in just one year, discovering a new therapeutic mechanism that can be engaged using an existing prescription drug. The discovered novel therapy surpasses the only approved drug in mouse models and is poised for upcoming clinical trials. Unravel has repeated this approach with other neurodevelopmental and neurodegenerative disorders.
As an example of how robust the approach is, Unravel’s lead drug prediction for a neurodegenerative disorder, generated and validated in under one year, has been nominated for the supporting foundation’s very first clinical trial. They are partnered with multiple foundations to develop custom repurposing and target discovery programs based on patient RNAseq data and enabling clinical trials in rare and ultra-rare disorders. (source)
Will this work for ALL SPATA5 and SPATA5L1 patients?
Not every variant can be tested, but the hope is that the treatment(s) found will work for everyone, although there is no gurantee. There's also no guarantee that the found treatment(s) would work the same from person to person, considering each case & set of symptoms are different.
What is the Process?
We'll try to explain this in an easy-to-understand way!
Step 1: Collect Patient Samples
In order to get the best results, Unravel needs patient samples! They need a minimum of 4 SPATA5 and 4 SPATA5L1 Nasal Swabs to analyze. Families can purchase a swab kit for $1350. A kit will include swabs for the patient and an unaffected parent or sibling of the same sex.
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Please understand, if you do not submit a sample, you will still benefit from this study. However, submitting a sample means your child's data will be studied, thus it being more likely whatever treatment is found would work for those who's samples were submitted.
Step 2: Analyze Patient RNA Samples & First Screen
Once all samples are received in the lab, Unravel will use the samples to predict patient-specific therapeutic mechanisms (drugs & compounds). They will take thousands of drugs already FDA-approved and on the market, plus individual compounds, and test them. The data from this analysis will result in data supporting one or more molecules for further testing.
Step 3: Create Animal Models & Test Top Candidates
Utilizing protocol from UMASS Boston, Unravel will create CRISPR-engineered tadpoles to represent SPATA5 and SPATA5L1 patients. They will then take the predicted list of therapeutics from Step 1, test them on the genetically modified tadpoles, and monitor how characteristics associated with the diseases change with treatment (seizures, hearing loss, motor function, dystonia/spasticity, etc).
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Why tadpoles? Mice are the preferred animal model, but tadpoles are a close second. Tadpoles are genetically very similar to humans, bust cost much less than mice and take a lot less time to engineer. They will be able to see physical symptoms in tadpoles, much like what we see in our kids, to truly get a good understanding of how certain drugs/compounds work.
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Depending on what the top drug candidates are and what they cost, there may be some additional costs associated with testing them on the tadpoles.
Step 4: A Treatment!
Depending on what drug(s)/compound(s) are found to be a potential treatment, there are a few ways that patients may be able to begin treatment. A doctor may be able to prescribe the drug, we may have to ask the FDA for compassionate use, or, if necessary, further testing may have to be done.
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If no drug is found, but individual compounds are found, Unravel Biosciences can work on engineering a NEW drug, specifically for treatment.
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What is SPATA5 and SPATA5L1?SPATA5 and SPATA5L1 are separate genes with a common ancestry and similar structure and function. Think of them like cousins. ​ Mutations in these genes cause two very similar rare genetic conditions: SPATA5 Disorder and SPATA5L1 Disorder.
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What is the lifespan of someone with SPATA5 or SPATA5L1?We know one of the first things running through your mind is how this changes your child's future. As far as we know, SPATA5 and SPATA5L1 Disorders do not directly result in any shortened lifespan. ​ With that being said, complications from these disorders do increase the risk. Epilepsy, Respiratory Issues, and Immunodeficiency can become serious and have resulted in the loss of a some SPATA5 and SPATA5L1 warriors. ​ All cases are different.
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What are the symptoms and signs of SPATA5 and SPATA5L1 Disorders?It's important to note that every case is different, and not everyone affected will experience all symptoms, and symptoms may be experienced at various degrees of severity. ​ Early Warning Signs: Hearing Loss Developmental Delay Intellectual Disability Epilepsy Spasticity Dystonia/Hypotonia Microcephaly Vision Impairment (typically Cortical Visual Impairment) Abnormal MRI Neurostorming Immunodeficiency
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Is there a treatment or a cure?That's why The SPATA Foundation was created: the hope of a cure. ​ There is no current cure or preferred treatment for SPATA5 or SPATA5L1 Disorder. Some medications may improve symptoms and increase quality of life, but this is dependent on individual symptoms & circumstances. For example, one anti-seizure medication may work great for some, but others may not respond to the same medication. The SPATA Foundation is committed to building relationships between patient families and researchers in order to pursue research towards treatment avenues. ​ We encourage you to join our efforts by sharing your story, sharing our story, and sharing our donation page.
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How is SPATA5 and SPATA5L1 Diagnosed?The symptoms of SPATA5 and SPATA5L1 are not enough alone to diagnose. Many genetic conditions share similar symptoms. The only sure way to diagnose SPATA5 or SPATA5L1 is via genetics. ​ SPATA5 can be detected via an Epilepsy Panel. SPATA5L1 can only be detected via Whole Exome Sequencing, unless there is a known family history, in which case targeted testing can be done.
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How many people have SPATA5 and SPATA5L1?Research published in 2015 reported 14 individuals with SPATA5 Disorder. However, we know there around 40-50 confirmed cases. Research published in 2021 reported 47 individuals with SPATA5L1 Disorder. 25/47 presented with neurological symptoms, while the other 22 presented with only hearing loss. As science advances and testing becomes more accessible, more families are being diagnosed and we expect to continue to find more affected people. ​ The SPATA Foundation was founded by parents of a child with SPATA5L1 because they've been in your shoes. ​ The first step in navigating this diagnosis is to connect with a community that understands exactly what you're going through.
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What does this mean for my future children?SPATA5 and SPATA5L1 are recessive genetic conditions. That means that both you AND your reproductive partner must be carriers of a mutation in order to have an affected child. Carriers have a 25% chance of each child they have being affected. Each child also has a 50% chance of being a carrier. Carrier: Has 1 mutated copy of the gene, but is not affected by symptoms Affected: Receives 2 mutated copies (or in some cases a deletion) that causes symptoms associated with the disorder Unaffected: Both genes are good
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What if I have more questions?Please feel free to email Mariah George directly at info@spatafoundation.org with any questions/concerns/comments.
