ITF Therapeutics was established with an important goal in mind: to build on the legacy of research at Italfarmaco, bring new therapeutic options that may address significant unmet medical needs to people living with rare diseases, and help make these options available for communities in the US.
According to the US National Institutes of Health (NIH), there are more than 7,000 known rare diseases that affect approximately 25 to 30 million people in the United States.1
Currently, there are treatments for only about 600 of these rare diseases.2
ITF Therapeutics and Italfarmaco are focused on changing that number.
Histone deacetylase (HDAC) inhibitors are a family of proteins that are involved in the post-translational modification of proteins. Our most advanced compound, givinostat (an HDAC inhibitor), has been approved by the FDA for the treatment of DMD in patients six years of age and older.
Our R&D group is working to identify second-generation inhibitors to specifically interfere with a defined subset of biological processes controlled by HDACs.
DMD is a rare neuromuscular disorder characterized by progressive muscle damage and weakness.3,4 It occurs almost exclusively in males due to its X-linked recessive genetic pattern.3,4 DMD incidence is approximately 1 in every 3,500-6,000 male births worldwide.5,6 Females are not typically affected, but they can be carriers of the genetic mutation and can have what is known as a dystrophinopathy.3,4
The disease is caused by mutations in the DMD gene resulting in the absence or non-functionality of dystrophin, a key structural protein that protects muscle cells from repeated contraction-induced damage.4 In DMD, muscles are vulnerable to damage from everyday activities.4 A normal healthy muscle can counteract muscle damage due to its innate ability to regenerate new muscle cells.7 However, the muscles of people with DMD are more susceptible to injury and their muscle regeneration is impaired.3,4 The body naturally tries to repair the damage, but continuous muscle fiber damage leads to chronic inflammation, and the muscle fibers are replaced by scarring (fibrous tissue) and fat deposits.7,8 Over time, the muscles lose their capability to regenerate and their ability to contract, resulting in loss of muscle mass and weakness.4
1. Rare Diseases. National Institutes of Health. https://www.nih.gov/about-nih/what-we-do/nih-turning-discovery-into-health/promise-precision-medicine/rare-diseases
2. Alves VM, Korn D, Pervitsky V, Thieme A, Capuzzi SJ, Baker N, Chirkova R, Ekins S, Muratov EN, Hickey A, Tropsha A. Knowledge-based approaches to drug discovery for rare diseases. Drug Discov Today. 2022;27(2):490-502.
3. Ryder S, Leadley RM, Armstrong N, Westwood M, de Kock S, Butt T, et al. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J Rare Dis. 2017;12(1):79.
4. Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17(3):251-67.
5. Bushby, K., R. Finkel, D. J. Birnkrant, L. E. Case, P. R. Clemens, L. Cripe, A. Kaul, K. Kinnett, C. McDonald, S. Pandya, J. Poysky, F. Shapiro, J. Tomezsko and C. Constantin. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010;9(1):77-93.
6. Duchenne Muscular Dystrophy. National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/duchenne-muscular-dystrophy/
7. Theret M, Rossi FMV, Contreras O. Evolving Roles of Muscle-Resident Fibro-Adipogenic Progenitors in Health, Regeneration, Neuromuscular Disorders, and Aging. Front Physiol. 2021;12:673404.
8. Giuliani G, Rosina M, Reggio A. Signaling pathways regulating the fate of fibro/adipogenic progenitors (FAPs) in skeletal muscle regeneration and disease. FEBS J. 2022;289(21):6484-6517.
