A Letter From Research Director Dr. André Weinstock
Thank you for your interest in Alport Syndrome Foundation’s (ASF’s) efforts to support academic research and a pharmaceutical pipeline for our rare genetic syndrome.
ASF is a US-based non-profit organization that is led by and dedicated to the community of patients & families affected by Alport syndrome. Our annual budget is made possible by contributions from our families and friends, and is aligned and prioritized to address the needs of our patient community. This alignment is documented in our Voice of the Patient report1 that emerged from our externally led patient-focused drug development (EL-PFDD) meeting we conducted in collaboration with National Kidney Foundation and the US Food and Drug Administration (FDA) in 2018.
Currently, the highest research priorities of our community are to make progress on the following:
- Continue the collection of human natural history data and longitudinal bio-samples to support a pharmaceutical pipeline for FDA approval of Alport-specific, on-label therapies—ameliorative and/or curative (ie, gene-based)—that extend our native kidney function while having a minimal negative impact on our quality of life.
- Conducting fundamental research into understudied Alport-syndromic phenotypes and pathologies such as:
- Mechanisms of hearing loss and retinal damage
- Pregnancy complications
- Prevalence of deep-intronic variants in COL4A3, COL4A4, and COL4A5 genes
- Fundamentals of collagen-IV folding, extracellular chaperoning, and matrix integration
A major challenge facing the Alport syndrome community is the persistent lack of accurate diagnoses.2-13 Although ASF’s membership has grown to nearly 10,000 patients, caregivers, and family members, the majority of people in the general population who have Alport syndrome are still unaware that they have it —due to being misdiagnosed or undiagnosed—and therefore do not receive the care that they need or receive benefit from our efforts and resources. Currently, there are no FDA-approved on-label therapies for Alport syndrome. Such a therapy would likely provide significantly more resources to improve awareness of the syndrome among clinicians and the general public. In turn, the diagnostic accuracy and clinical treatment of individuals with Alport syndrome would both be greatly increased through the adoption of genetic screening as a primary kidney disease diagnostic tool in lieu of the current practice of invasive kidney biopsies and the reflexive prescribing of ineffective steroids and immunosuppressants.
Throughout our research endeavors, the ASF takes care to ensure alignment with the latest FDA guidances on the conduct of rare, genetic, and/or kidney clinical trials and associated nonclinical research.14-16 In order to aid the exploration of potential therapies and cures for Alport syndrome we have directed a significant amount of ASF’s resources in the past several years to establish and expand our natural history registry, a human sample biobank, a collection of diverse animal and cellular models, a collaborative and extensive network of expert researchers and clinicians, and a curated patient engagement policy.
ASF is open to and familiar with entering confidentiality/nondisclosure agreements with various therapeutic research and development sponsors and clinical contract research organizations. Included below are more details about how ASF collaborates with researchers and the biopharmaceutical industry to advance our common goals.
To initiate a conversation, please contact me at [email protected].
Best,
André Weinstock, PhD
ASF Research Director
Alport Syndrome patient
RESOURCES FOR RESEARCH AND CLINICAL DEVELOPMENT
Click the “+” icon to expand subsection text below.
- The ASF-sponsored Alport Patient Registry is an IRB-approved, noninterventional, self-reported, ambispective, longitudinal natural history study. Data are collected from pediatric and adult Alport syndrome patients in the US via a secure online platform. The Registry’s Alport-centric data dictionary includes genotypes verified by a qualified geneticist within the HIPAA-compliant platform, phenotypes (eGFR, family history, audiograms, and dialysis and transplant details), family history, diagnostic journey history, and basic treatment history (RAASi and SGLT2i dosing/side effects; clinical trial participation history).
- Access requests for mining the deidentified registry data are reviewed by the Registry’s scientific advisory board. For more information, contact [email protected].
- The ASF sponsors an ancillary natural history study of Alport syndrome and collagen-IV-opathies in partnership with the NEPTUNE Consortium at the University of Michigan. This study collects blood and urine samples, performs whole genome sequencing, and records family history and longitudinal kidney health data points over a 3-year period from more than 60 pre-kidney–failure Alport patients at more than 20 clinical sites in the US and Canada.
- For study details and/or how to request access to these longitudinal biosamples and data, contact [email protected].
Through its extensive understanding of current and emerging nonclinical research projects, the ASF can offer:
- Guidance on the availability, sources for, and effectiveness of existing Alport-specific animal models
- Introductions to international specialists with expertise in specific Alport research areas
- Links to archived literature related to Alport syndrome genetics, its known symptoms, underlying histopathology, recommended treatment and outcomes, and more
Contact [email protected] for more information.
Contact [email protected] for information regarding:
- Requesting recommendations for/introductions to potential clinical investigators and study sites
- Requesting customized “Listening Sessions” with patients and caregivers to understand the patient perspective and/or to receive clinical trial design input
- Requesting review and feedback on patient-facing materials
- Accessing/contributing to listings of currently active and/or enrolling clinical studies (In 2023, alportsyndrome.org had 69,000 visitors and 181,000 page views)
- Messaging patients, caregivers, and clinicians in the US about actively enrolling clinical studies via direct email addresses and our social media channels, as well as providing information to patients who contact ASF for clinical trial information. Messages can be targeted by geographic region. (ASF’s monthly e-news is sent to more than 9,000 members.)
- Education and awareness provided by the ASF to its community regarding clinical trial participation, sponsor versus patient expectations, and patients’ rights and responsibilities. Information is provided through our website, videos, and our in-person and virtual Alport Connect gatherings with patients, families, and caregivers.
- National Kidney Foundation and Alport Syndrome Foundation. The Voice of the Patient: Externally Led Patient-Focused Drug Development Meeting on Alport Syndrome. Nov 2019. Accessed 17-JAN-2024. Available at: https://www.fda.gov/media/132537/download
- Groopman EE, Marasa M, Cameron-Christie S, et al. Diagnostic utility of exome sequencing for kidney disease. N Engl J Med. 2019;380(2):142-151. doi:10.1056/NEJMoa1806891
- Mann N, Braun DA, Amann K, et al. Whole-Exome sequencing enables a precision medicine approach for kidney transplant recipients. J Am Soc Nephrol. 2019;30(2):201-215. doi:0.1681/ASN.2018060575
- Wang M, Chun J, Genovese G, et al. Contributions of rare gene variants to familial and sporadic FSGS. J Am Soc Nephrol. 2019;30(9):1625-40. doi:10.1681/ASN.2019020152
- Gibson J, Fieldhouse R, Chan MMY, et al. Prevalence estimates of predicted pathogenic COL4A3-COL4A5variants in a population sequencing database and their implications for Alport Syndrome. J Am Soc Nephrol. 2021;32(9):2273-2290. doi:10.1681/ASN.2020071065
- Gregorio V, Caparali EB, Shojaei A, et al. Alport syndrome: Clinical spectrum and therapeutic advances. Kidney Med. 2023;5(5):100631. doi:10.1016/j.xkme.2023.100631
- Becherucci F, Landini S, Palazzo V, et al. A clinical workflow for cost-saving high-rate diagnosis of genetic kidney diseases. J Am Soc Nephrol. 2023;34(4):706-720. doi:10.1681/ASN.0000000000000076
- Robert T, Raymond L, Dancer M, et al. Beyond the kidney biopsy: Genomic approach to undetermined kidney diseases. Clin Kidney J. 2023;17(1):sfad099. doi:10.1093/ckj/sfad099
- Solanki KV, Hu Y, Moore BS, et al. The phenotypic spectrum of COL4A3 Kidney Int Rep. 2023;8(10):2088-2099. doi:10.1016/j.ekir.2023.07.010
- Rheault MN, McLaughlin HM, Mitchell A, et al. COL4A gene variants are common in children with hematuria and a family history of kidney disease. Pediatr Nephrol. 2023;38(11):3625-3633. doi:10.1007/s00467-023-05993-z
- Dahl NK, Bloom MS, Chebib FT, et al. The clinical utility of genetic testing in the diagnosis and management of adults with chronic kidney disease. J Am Soc Nephrol. 2023;34(12):2039-2050. doi:10.1681/ASN.0000000000000249
- US Food and Drug Administration. Rare Diseases: Natural History Studies for Drug Development: Draft Guidance for Industry. March 2019. Accessed 17-JAN-2024. Available at: https://www.fda.gov/media/122425/download
- US Food and Drug Administration. Human Gene Therapy for Rare Diseases: Guidance for Industry. January 2020. Accessed 17-JAN-2024. Available at: https://www.fda.gov/media/113807/download
- US Food and Drug Administration. Rare Diseases: Considerations for the Development of Drugs and Biological Products: Guidance for Industry. December 2023. Accessed 17-JAN-2024. Available at: https://www.fda.gov/media/119757/download