Adenosine deaminase deficiency

Researchers at the non-profit n-Lorem discovered and developed a personalised ASO therapy to treat a rare neurological disease. Credit: SurfsUp via Shutterstock. A patient with a rare progressive neurodegenerative disorder receiving a personalised experimental antisense oligonucleotide (ASO) treatment developed by the non-profit n-Lorem has reported improvements in seizure severity and quality of life. The patient, named Susannah, has a rare condition called KIF1A-associated neurological disorder (KAND). US-based non-profit n-Lorem developed a personalised, experimental ASO medicine specific to Susannah’s genetic mutation. After receiving her first dose of the personalised medicine, her seizures fell to under 30 per week and she has remained stable. KAND is caused by mutations in the KIF1A gene, leading to progressive motor impairments, developmental delays, and cognitive difficulties. Management of KAND mainly focuses on addressing symptoms and improving quality of life through supportive therapies, like speech or physical therapy. There are no other therapies for KAND in clinical development, as per GlobalData’s Pharma Intelligence Center. GlobalData is the parent company of Pharmaceutical Technology . Following the ASO treatment, the patient’s ability to walk also improved after one month; compared to having an average of 26.2 falls per day before treatment, she now experiences up to seven falls daily, with many days without any falls. See Also: Eli Lilly boosts sales forecast by $3bn as diabetes and weight loss drugs propel revenue Recursion and Exscientia merge to form drug discovery company Data from the study published in Nature Medicine also detail notable advancements in speech, attention, group interaction, and motor functions, while the patient’s cognitive abilities have remained stable. Susannah has continued on the ASO treatment for 20 months, with a favourable safety and tolerability profile. ASO therapies work by using short, synthetic strands of nucleic acids to target and modify specific genes, reducing the production of harmful proteins or correcting genetic defects. The treatment developed by n-Lorem targets and corrects the harmful version of the KIF1A gene. Founded by former Ionis Pharmaceuticals ’ CEO Stanley Crooke, n-Lorem aims to bring ASO therapies to patients who are diagnosed with a disease that is found in less than 30 people. Research physicians submit an application to the non-profit, which examines if the patient’s genetic mutation is amendable to the ASO technology. More than 130 patient applications have so far been approved by the organisation for a range of different mutations. There has been an increase in the number of nonprofits developing rare disease medications where the patient population size is too small for commercialisation. Italian research charity Telethon Foundation manufactures and distributes Strimvelis, a gene therapy for rare disease adenosine deaminase severe combined immunodeficiency (ADA-SCiD). The non-profit took over development after it was dropped by its pharmaceutical company in 2022, allowing patients to receive treatment. ASO therapies have long been investigated in rare diseases because they target the cause of disease at the molecular level. Researchers have also developed candidates that are approved to treat conditions affecting larger patient populations. Biogen ’s ASO Spinraza (nusinersen) secured approval for treating the movement disorder spinal muscular atrophy in 2016, pulling in $610.5m in sales in 2023 as per the company’s financials. In the announcement accompanying the case study, n-Lorem’s CEO Stanley Crooke said: “Prior to treatment, Susannah’s disease had progressed to her being mostly in a wheelchair, approaching nonverbal with debilitating seizures that limited her and her family’s quality of life. Susannah has now been on treatment for more than 20 months and we continue to observe improvements in her mobility, neurological function, and quality of life.” The non-profit, which launched in 2020, is also conducting a KIF1A outcome measures, assessments, longitudinal and endpoints (KOALA) study to understand how KAND symptoms develop and change over time.

The FDA’s rare disease innovation hub aims to streamline rare disease drug development. Credit: PeopleImages.com – Yuri A via Shutterstock. A new rare disease innovation hub set up by the US Food and Drug Administration (FDA) aims to expedite the development and approval of orphan drugs. Rare disease clinical trials can be tricky to navigate, especially for conditions with very few patients. Moreover, even after clinical success, some therapies for rare diseases have been dropped by companies due to the high development costs. The FDA’s hub will act as a central point of connection and engagement with the rare disease community, aiding the navigation of FDA-related concerns. It will enhance inter-centre collaboration on scientific, clinical, and policy issues in rare disease product development, said the agency. It also aims to advance novel endpoints, biomarkers, trial designs, real-world evidence, and statistical methods. The hub will be co-led by Dr. Patrizia Cavazzoni, director at the Center for Drug Evaluation and Research (CDER), and Dr. Peter Marks, director at the Center for Biologics Evaluation and Research (CBER). In 2023, over half of all novel drugs and biologics approved by the FDA’s CDER and CBER were to treat or prevent a rare disease. While there have been important advances in treatments for rare diseases, more needs to be done, said the co-leaders in the announcement: See Also: Conflict means millions of children are missing vaccinations, UN says Moderna and Mitsubishi Tanabe link on mRNA vaccines in Japan “We see huge potential in establishing a new model, within the FDA, to leverage cross-agency expertise and greatly enhance our inter-centre connectivity to spur the development of treatments for rare diseases.” Such initiatives can be helpful to address concerns raised by key stakeholders in the field. The Italian research charity Telethon Foundation manufactures and distributes the gene therapy Strimvelis, which is used to treat the rare disease adenosine deaminase severe combined immunodeficiency (ADA-SCiD). Speaking to Pharmaceutical Technology , Francesca Pasinelli, general manager of Telethon Foundation, highlighted how one regulatory bottleneck in rare disease development affects operations. “Overall resource challenges faced by regulatory authorities extend the timelines for obtaining feedback to facilitate the development of products. We therefore understand that it might be difficult for regulatory authorities to speed up the process or even rethink some of the procedures when experts are lacking.” In order to advance treatments for patients with rare diseases, the FDA says it will hold an open public meeting later this year that will include the establishment of a public docket. This aims to provide further information about the vision for the Hub and get feedback from the community to help shape the Hub’s priorities and initiatives.

Potential to be the first IVD for the screening of Wilson Disease, Wiskott-Aldrich Syndrome, X-linked Agammaglobulinemia and Adenosine Deaminase Deficiency SEATTLE, March 29, 2024 /PRNewswire/ -- Key Proteo, a pioneering proteomics diagnostics company specializing in the enhanced early detection of rare but treatable genetic disorders, today announced that it has submitted a de novo classification request to the U.S. Food and Drug Administration (FDA) for its first in vitro diagnostic Key Proteo Newborn Screening Kit. The novel proteomics-based screening panel addresses a critical, unmet need to aid in the early identification of four treatable rare genetic disorders that current newborn screening programs do not typically test for, including Wilson Disease (WD), Wiskott-Aldrich Syndrome (WAS), X-linked Agammaglobulinemia (XLA) and Adenosine Deaminase Deficiency (ADA). Early screening has the potential to enable timely intervention that can help change the clinical trajectory and relieve the burden of disease for patients and their families afflicted by these potentially devastating disorders. The submission of Key Proteo's Newborn Screening Kit 1 comes after screening over 22,000 newborn samples in an ongoing pilot study in Washington state. Subsequently, Key Proteo successfully completed a clinical study that included 3,294 newborn samples analyzed at 3 sites across North America. "We are excited to lead the charge towards changing the clinical course of treatable rare genetic disorders that are currently being missed," said Mark Willig, President and CEO of Key Proteo. "Enhanced early screening is key to enabling clinical interventions that can significantly help reduce morbidity and mortality. I am extremely proud of the tireless efforts that our team has made over the past five years to reach this important milestone not just for our company, but for the patients and their families that will benefit from these life-altering screening tools." With its initial focus on addressing unmet needs for WD, WAS, XLA and ADA in the newborn screening space, nearly 100 treatable genetic disorders have been identified that could potentially be adapted to Key Proteo's dynamic proteomics-based platform. The in vitro diagnostic Key Proteo Newborn Screening Kit 1 will only be available for commercialization once the FDA has completed its process. Currently, Key Proteo Newborn Screening Kit 1 is available as an RUO offering. In parallel path, Key Proteo is also expanding its operations to include a CLIA-certified laboratory to serve unaddressed newborn screening needs among public health laboratories, reference laboratories, hospital laboratories and other providers associated with neonatal care that may prefer to send-out for these and other critically important newborn screening tests. ABOUT WILSON DISEASE, WISKOTT-ALDRICH SYNDROME, XLA and ADA Wilson Disease, affecting approximately 1 in 30,000 individuals, is characterized by excess copper accumulation in the liver, brain, and eyes, and can lead to liver disease, central nervous system dysfunction and death. Timely diagnosis and treatment are vital to prevent long-term disability and life-threatening complications. Impacting 1 in 100,000, Wiskott-Aldrich Syndrome is characterized by immunodeficiency and impaired blood clotting. Symptoms include bruising, susceptibility to infections and immune and inflammatory disorders, and heightened cancer risk. Eczema often accompanies the syndrome. WAS patients face increased vulnerability to infections, bleeding, and cancers, often leading to premature mortality. X-linked Agammaglobulinemia, impacting around 1 in 250,000 individuals, mainly males, is marked by severely low immunoglobulin levels. Typically, symptoms manifest as recurrent bacterial infections from around 6 months of age, with commonly diagnosed infections including lung, ear, sinus, eye, and skin infections, along with those linked to chronic diarrhea. Adenosine Deaminase Deficiency (ADA), impacting roughly 1 in 500,000 individuals, is a primary cause of severe combined immunodeficiency (SCID), impairing the body's ability to combat infections. Symptoms typically emerge before 6 months, ranging from pneumonia to chronic diarrhea and delayed development. While most symptoms surface early, some may manifest later in life. ABOUT KEY PROTEO Key Proteo is on a mission to save lives and relieve the burden of disease for patients and their families afflicted by rare but treatable genetic disorders through early screening. Many treatable genetic disorders are difficult to detect, but when found early, intervention can be enabled to help change the clinical course. With its initial focus on newborns, Key Proteo's dynamic proteomics-based platform can be adapted to screen for rare but treatable genetic disorders across other patient populations. Key Proteo's patent-pending Immuno-SRM platform and associated reagent kits can perform targeted proteomic analysis of extremely low abundance peptide biomarkers from a few drops of blood. This proprietary technology expands the scope of detecting previously undetectable genetic disorders in newborns with high accuracy, effectiveness and efficiency, and has demonstrated faster turnaround times and lower costs when compared to next-generation sequencing (NGS). FORWARD-LOOKING STATEMENTS Certain information contained in this press release constitutes forward-looking statements. These forward-looking statements involve a number of risks and uncertainties that could cause actual future results to differ materially from those anticipated. Forward-looking statements represent the Company's estimates only as of the date such statements are made and the Company undertakes no obligation to update forward-looking statements except as required by applicable securities laws. Readers are cautioned that forward-looking statements are not guarantees of future performance and are cautioned not to place undue reliance on any forward-looking statements. For more information, visit . #KeyProteo #DeNovoClassification #NewbornScreening #RareDisease #WilsonDisease #WilsonDiseaseAssociation #WiskottAldrichSyndrome #XLA #AdenosineDeaminaseDeficiency #ImmuneDeficiencyFoundation #Proteomics #Biotech #VentureCapital #LifeSciences #HealthTech #BioTechNews CONTACT Sean Sandin Chief Operating Officer [email protected] SOURCE Key Proteo