Date: 2014-10-28
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 9th International Conference on Frontotemporal Dementias
Company: Forum Pharmaceuticals (USA - MA)
Product: FRM-0334
Action
mechanism: FRM-0334 is a histone deacetylase (HDAC) inhibitor that enhances gene transcription of the healthy GRN gene copy and may have the promise to positively affect neuronal survival for patients with a genetic variation of frontotemporal dementia (FTD) associated with a granulin deficiency (FTD-GRN). FTD-GRN is a rare, early-onset and rapidly progressive neurodegenerative brain disorder that can affect behavior, cognition, language and motor skills, due to a reduction in the progranulin protein. Five studies were presented, featuring investigative data on FRM-0334 pharmacology, screening and identification of additional progranulin modulators, pathways to increase progranulin release, potential biomarker selection and therapeutic approaches to treating the disease.
Disease: frontotemporal dementia (FTD) associated with a granulin deficiency
Therapeutic area: Rare diseases - Neurodegenerative diseases
Country:
Trial details:
Latest
news: * On October 28, 2014, Forum Pharmaceuticals (previously known as EnVivo Pharmaceuticals), a biopharmaceutical company singularly focused on the development and delivery of innovative medicines to treat serious brain diseases, announced results from FRM-0334 research studies at the 9th International Conference on Frontotemporal Dementias. “As part of Forum’s mission to develop therapies for serious brain diseases, we are investigating FRM-0334 for the treatment of granulin-associated FTD, a rare genetic disease that strikes many patients in the prime of life, progresses rapidly and is ultimately fatal,” said Deborah Dunsire, M.D., President and Chief Executive Officer of FORUM Pharmaceuticals. “No therapies currently exist to address the immense needs of FTD patients and families, and FORUM is excited to share results from these promising FRM-0334 studies with leaders and experts in the research community at the 9th International Conference on Frontotemporal Dementias. As an earlier-stage candidate in our robust product pipeline, FRM-0334 complements FORUM’s Phase 3 encenicline development program for Alzheimer\'s disease and schizophrenia. We plan to initiate a Phase 2 clinical trial for FRM-0334 later this year.” In the oral presentation, “The clinical stage HDAC inhibitor FRM-0334 induces progranulin in rodent brain and in FTLD-GRN patient-derived lymphoblasts,” Holger Patzke, Ph.D., Senior Director, Biology, at Forum, described the company’s development of highly brain penetrant HDAC inhibitors to epigenetically target brain function. Pharmacology results from lead compound FRM-0334 demonstrated increased granulin expression in normal animals and up to five-fold increased granulin expression in cultured rat nerve cells and in cell lines derived from patients carrying the granulin mutations.
Additional presentations at the conference focused on screening and identification of novel progranulin modulators and pathways to increase progranulin release, potential biomarker selection and potential therapeutic approaches to treating FTD-GRN. The poster, “A phenotypic screen of a mouse microglial cell line reveals novel mechanisms to modulate levels of progranulin,” described the role of phenotypic screening and methods of mapping and validation studies in the identification of progranulin modulators. The study,“Depletion of cellular cholesterol levels results in increased progranulin secretion and altered progranulin glycosylation,” detailed how cellular cholesterol depletion may provide a pathway for progranulin induction, thereby potentially offering a novel therapeutic approach for FTD-GRN. Another potential therapeutic approach to treating FTD-GRN was described in, “Anti-inflammatory transforming growth factor β signaling increase microglial progranulin levels,” which demonstrated data supporting the hypothesis that progranulin may have a role in regulating CNS inflammation. The study, “Assessment of variability of progranulin concentrations in human cerebrospinal fluid (CSF),” characterized the longitudinal levels of PGRN in CSF in subjects 45-65 years of age, supporting future development of clinical biomarkers and calculation of clinical trial size estimates.
Full content of all abstracts may be found at the 9th International Conference on Frontotemporal Dementias.
