Development of Epigenetic Therapies for Rare Diseases
Our researchers have expertise and research background in understanding the contribution of epigenetic changes to rare diseases, allowing us to provide better molecular tools to help our clients improve the diagnosis and treatment of rare diseases. We are committed to exploring new epigenetic targets and developing and testing epigenetic drugs with longer half-lives, better bioavailability, and improved safety profiles, opening new avenues for the treatment of rare diseases.
Epigenetic Therapies for Rare Diseases
Epigenetics is defined as the study of heritable changes in gene expression that occur independently of changes in the original DNA sequence. Known epigenetic mechanisms are usually divided into three categories, including DNA methylation, histone modification, and RNA-associated silencing. Studies on pathogenesis have shown that some rare diseases such as Rett syndrome (RTT), immunodeficiency centromere instability facial syndrome 1 (ICF1), and Rubinstein-Tabi syndrome (RTS) have epigenetic components or involve epigenetically regulated genes.
Dysregulation of the epigenome drives an abnormal transcriptional program that leads to the development and progression of several rare diseases. In recent years, a number of researchers are attempting to develop novel therapies starting from epigenetics, aiming to treat diseases using drugs or other technologies that affect the epigenome. Epigenetic therapies offer a potential way to directly affect pathways that are affected by epigenetic mechanisms. In contrast to gene therapy, epigenetic therapies are reversible, which means they have great potential in targeted therapy.
Fig. 1 Overview of the new approaches to epigenetic therapies. (Majchrzak-Celińska A, et al., 2021)
Our Epigenetic Therapy Development Services for Rare Diseases
We provide expert technical support to help our clients flexibly and scientifically apply epigenetic tools at the clinical level in monotherapy and combination therapies to develop new ways to combine epigenetic therapies with other therapies. Furthermore, we design clinical trials for our clients to run these new strategies to improve current epigenetic therapies. Our specific scientific services include, but are not limited to:
- Development of DNA methyltransferase inhibitors (DNMTi)
Numerous DNMTi have been successfully launched, demonstrating their potential as targeted therapies. We help our clients develop new, more efficient nucleoside and non-nucleoside DNMTis from different pathways and evaluate their effectiveness in the treatment of rare diseases. - Development of histone deacetylase inhibitors (HDACi)
HDACi are significant bioactive compounds for cancer treatment. We help our clients develop HDACis for targeted tumor therapy. We address drug resistance to HDACi by combining HDACi with other anti-cancer drugs, such as combining HDACi with PARP inhibitors, proteasome inhibitors, mTOR inhibitors, antimetabolites, radiotherapy, or monoclonal antibodies. Moreover, we help clients design dual inhibitors, which have two active motives targeting different epigenetic proteins within the same molecule to improve cancer treatment. - Development and test of drugs against novel epigenetic targets
We use live cell analysis to help our clients screen for drugs with the same degree of epigenetic reprogramming as DNMTi to discover new epigenetic drugs. For example, developing cyclin-dependent kinases as epigenetic therapeutic targets. - Development of drug combinations to enhance the efficacy of known epigenetic drugs
- We help clients develop and test combinations of DNMTi with HDACi to improve the efficacy of each of the single agents., such as the combination of DNMTi (azacitidine) and HDAC6i (NextA).
- We use several DNMTi and HDACi in combination with various chemotherapeutic agents to achieve synergy and reverse acquired therapeutic resistance.
- We help clients develop and test combinations of epigenetic drugs with immunotherapies to enhance anti-tumor immune responses.
- Epigenetic editing services
We offer epigenome editing technologies such as CRISPR/dCas9 to specifically and efficiently modify individual chromatin markers at a defined region, which offers the possibility of correcting epigenetic mutations associated with rare diseases.
As a biotechnology company in the rare disease space, our researchers have made many efforts to develop, characterize, and translate fundamental knowledge into epigenetic therapies. We are well-positioned to help our clients develop new genetic therapies and improve current epigenetic therapies for rare diseases. If you are interested in our epigenetic therapy development services, please contact us for more details.
References
- Nepali, K.; Liou, J. P. Recent developments in epigenetic cancer therapeutics: Clinical advancement and emerging trends. Journal of Biomedical Science, 2021, 28(1): 1-58.
- Majchrzak-Celińska A, et al. Novel approaches to epigenetic therapies: from drug combinations to epigenetic editing. Genes, 2021, 12(2): 208.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.