Rady Children’s and Takeda Partner to Develop Treatments for Rare Genetic Diseases

2-year-old Sebastiana Manuel has been among patients at Rady Children's Institute for Genomic Medicine (RCIGM) who have benefited from rapid whole genome. RCIGM researchers have developed an automated pipeline that has been shown in a new study to deliver a provisional finding in a median time of less than 24 hours. [Rady Children's Institute for Genomic Medicine]

Rady Children’s Institute for Genomic Medicine announced this week that it will partner with Takeda to develop targeted therapeutics for rare genetic diseases.

The San Diego based institute is part of Rady Children’s Hospital-San Diego and is well known for its ground-breaking research on rare genetic diseases. It also provides diagnostic genomic services to 70 different children’s hospitals in the U.S. and in emergencies can carry out ultra-fast genomic sequencing within a few days, something rarely seen elsewhere.

“While we’ve made great progress in diagnosing rare genetic diseases for critically ill newborns and children, only an estimated 10% of childhood genetic diseases currently have effective treatments,” Stephen Kingsmore, president and CEO of the Rady Institute for Genomic Medicine, told Clinical Omics.

“The collaboration with Takeda is our Institute’s first effort focused on ending the therapeutic odyssey for patients with rare disease.”

Rady Children’s will be providing aggregated, de-identified genomic and phenotypic data derived from its whole genome sequencing cases, as part of the collaboration – detailed specifics of which have not been disclosed.

“We will review these cases collectively to extract longitudinal data and identify natural history and progression for specific disease cohorts. Takeda will oversee the drug discovery and development of potential targeted therapeutics resulting from the program,” explains Kingsmore.

“Rady Children’s Institute for Genomic Medicine and Takeda scientists will also collaborate on developing new methods to analyze these datasets,” adds Dan Curran, Head of the Rare Genetics and Hematology Therapeutic Area Unit at Takeda.

Many rare genetic diseases are only experienced by small numbers of children and finding a diagnosis, let alone a treatment, can take months if not years. The researchers at Rady Children’s hope that by combining their knowledge and data about genetic diseases with the drug development knowledge and resources of the Japanese big pharma they can help increase the number of therapies available for these children.

“At Takeda, one of our core therapeutic focus areas is rare genetics and hematology where we are investigating medicines for several different rare genetic diseases,” says Curran. “Gaining access to the breadth of data that Rady Children’s Institute for Genomic Medicine has cultivated will hopefully allow us to derive new insights on how childhood-onset diseases manifest, enabling us to more quickly develop transformative therapies for the families who desperately need them.”

Research done at Rady Children’s has already led to potential treatment options being uncovered for rare genetic diseases. For example, a study published in 2019 showed that variants in the VARS gene were behind a rare, severe brain disorder known as progressive neurodevelopmental epileptic encephalopathy. Children with this disease have a defect in the enzyme responsible for making the amino acid valine, which helps maintain cellular health. The Rady Children’s study findings show that treatments that could help synthesize valine could help treat these children.

Research into genetic forms of cardiomyopathy carried out at the institute is also helping to find treatments for individuals with this cardiac condition and Rady Children’s researchers have been involved in recent efforts to design antisense oligonucleotides (ASOs) to target rare diseases such as spinal muscular atrophy, as well as other even rarer conditions.

Kingsmore emphasizes that diagnosis is always important, even if there may not yet be drugs available to treat a condition. “Almost every diagnosis leads to changes in management – but the idea that it is always an effective drug is a misconception. It may be physical therapy, behavioral therapy, diet change, speech therapy, hearing aids, mobility aids, other assistive devices, educational adjustments, help with vision, genetic counseling, social services, surgical interventions, or palliative care,” he explains.

“When diagnosis leads to a change in medical management, it leads to an improved healthcare experience for the child, their parents, and the attending physicians. Definitive diagnoses, even in the absence of available treatment, can eliminate further unneeded tests or procedures.”

Precision medicine in these cases is multi-factorial, as shown by California’s Project Baby Bear, which Rady Children’s participated in. Published last year, this project involved rapid sequencing of newborns to help make important treatment and therapeutic decisions quickly. The results of the study showed that using this kind of sequencing approach can actually save money, through shorter hospital stays and less procedures, and even pointed the way to suitable therapies for some of the infants involved.

Rady Children’s now hopes that the large amount of data it has collected over the years can help Takeda discover or develop targeted therapies for more children with rare diseases.

“For many, many childhood genetic diseases there is insufficient knowledge of the natural history of the condition. Greater knowledge of the underpinnings of genetic disease is a starting point for therapeutic development or therapeutic repurposing,” says Kingsmore.

“Many genetic diseases lack knowledge even of incidence. There is a dearth of knowledge of disease progression, disease complications or disease response to trials of therapy. Many genetic diseases are lumped, and split based on historical circumstance. Without basal knowledge it is extremely difficult to prioritize diseases or indications for drug development or to know what specific endpoints are meaningful and which may impact quality and quantity of life.”

Takeda wants to bring the same precision medicine principles currently being applied to diagnose and treat cancers to rare diseases. “We have been investing in generating and accessing deeply characterized, large genomic data sets and establishing genomic capabilities. As we have seen with oncology, the ability to target therapies to specific disease drivers can have profound impact on outcomes and we see real promise in applying those same principles to rare genetic diseases,” concludes Curran.

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