Development of a Precision Neurotherapeutics Program at Columbia
Clinical Genetics and Therapeutics
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Primary Categories:
- Genomic Medicine
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Secondary Categories:
- Genomic Medicine
Introduction:
The Precision Neurotherapeutics Program (PNTP) at Columbia’s Department of Neurology aims to ensure universal access to FDA-approved therapies, clinical trials, and emerging N-of-1 options for neurogenetic patients in our department.
One of the most striking advances in precision medicine is the development of treatments tailored to specific genetic variants and underlying mechanisms driving neurogenetic disorders. Examples of such therapeutic approaches include ASOs, gene delivery and enzyme replacement therapies. For more common neurogenetic disorders, such as spinal muscular atrophy and Duchenne muscular dystrophy, where the prevalence predicts a profitable drug, development has occurred through traditional pathways via biotech and pharmaceutical investment. However, companies are unlikely to undertake development programs for rare and ultra-rare neurogenetic disorders because even a successful product would lack commercial viability. Fortunately, the cost of genetic therapy development is decreasing rapidly, and it is now feasible for academic medical centers like Columbia to partner with collaborators to develop, test, and bring these medicines to the clinical testing stage. Outsourcing the task of keeping up with expanding FDA-approved therapies, clinical trials, and complex regulations to a specialized team improves treatment access, as non-specialist clinicians often lack the bandwidth to handle these tasks.
Methods:
Neurologists, neuroscientists and genetic counselors working in the PNTP are conducting a retrospective chart review to identify and database all patients with defined neurogenetic disorders followed in the Department in the last 10 years. Chart review assesses whether patients have been considered for FDA-approved medications and preliminarily screened for eligibility for enrolling trials. Suitability for N-of-1 genetic therapy development, such as ASO or gene replacement therapy is considered. Once potential interventions are identified, the PNTP contacts the clinicians to recommend next steps, or to collaborate on individualized therapy development. If an experimental treatment is identified, we work with our partners to submit an Investigational New Drug (IND) application to the FDA and develop a separate IRB protocol for dosing/treatment administration.
Results:
From clinician and genetic counselor patient trackers we identified about 1,900 individuals with neurogenetic diagnoses followed in the Department. Chart review is ongoing, and final results will be presented at the conference. Preliminary screening has identified 351 patients with possible next steps, including 40 with pediatric neurodevelopmental phenotypes being considered for ASO knock-down strategies. Twenty-one individuals may be eligible for ongoing interventional clinical trials identified via ClinicalTrials.gov. Nineteen individuals were identified as already receiving targeted treatment clinically or through separate research studies. Among these, six pediatric patients with ultra-rare conditions (KIF1A, ATN1 and HNRNPH2) are being treated with ASOs developed by the n-Lorem foundation.
Conclusion:
A dedicated neurotherapeutics program can improve access to precision medicine by creating an infrastructure to efficiently identify patients eligible for personalized and existing therapies.
The Precision Neurotherapeutics Program (PNTP) at Columbia’s Department of Neurology aims to ensure universal access to FDA-approved therapies, clinical trials, and emerging N-of-1 options for neurogenetic patients in our department.
One of the most striking advances in precision medicine is the development of treatments tailored to specific genetic variants and underlying mechanisms driving neurogenetic disorders. Examples of such therapeutic approaches include ASOs, gene delivery and enzyme replacement therapies. For more common neurogenetic disorders, such as spinal muscular atrophy and Duchenne muscular dystrophy, where the prevalence predicts a profitable drug, development has occurred through traditional pathways via biotech and pharmaceutical investment. However, companies are unlikely to undertake development programs for rare and ultra-rare neurogenetic disorders because even a successful product would lack commercial viability. Fortunately, the cost of genetic therapy development is decreasing rapidly, and it is now feasible for academic medical centers like Columbia to partner with collaborators to develop, test, and bring these medicines to the clinical testing stage. Outsourcing the task of keeping up with expanding FDA-approved therapies, clinical trials, and complex regulations to a specialized team improves treatment access, as non-specialist clinicians often lack the bandwidth to handle these tasks.
Methods:
Neurologists, neuroscientists and genetic counselors working in the PNTP are conducting a retrospective chart review to identify and database all patients with defined neurogenetic disorders followed in the Department in the last 10 years. Chart review assesses whether patients have been considered for FDA-approved medications and preliminarily screened for eligibility for enrolling trials. Suitability for N-of-1 genetic therapy development, such as ASO or gene replacement therapy is considered. Once potential interventions are identified, the PNTP contacts the clinicians to recommend next steps, or to collaborate on individualized therapy development. If an experimental treatment is identified, we work with our partners to submit an Investigational New Drug (IND) application to the FDA and develop a separate IRB protocol for dosing/treatment administration.
Results:
From clinician and genetic counselor patient trackers we identified about 1,900 individuals with neurogenetic diagnoses followed in the Department. Chart review is ongoing, and final results will be presented at the conference. Preliminary screening has identified 351 patients with possible next steps, including 40 with pediatric neurodevelopmental phenotypes being considered for ASO knock-down strategies. Twenty-one individuals may be eligible for ongoing interventional clinical trials identified via ClinicalTrials.gov. Nineteen individuals were identified as already receiving targeted treatment clinically or through separate research studies. Among these, six pediatric patients with ultra-rare conditions (KIF1A, ATN1 and HNRNPH2) are being treated with ASOs developed by the n-Lorem foundation.
Conclusion:
A dedicated neurotherapeutics program can improve access to precision medicine by creating an infrastructure to efficiently identify patients eligible for personalized and existing therapies.