Moderna Therapeutics, Cambridge, MA

MMA produces unique protein modifications that contribute to disease

Moderna Therapeutics is a seven-year old company focused exclusively on developing medicines and vaccines using messenger RNA (mRNA). mRNA plays a critical role in human biology, carrying the “blueprint” of proteins from the genetic code contained in DNA. When a person has a genetic condition, the person’s DNA makes certain mRNA with some mistakes in it, and the resulting protein does not work correctly or at all. Moderna is making mRNA to make normal functioning protein as a potential therapy for certain diseases. Unlike gene therapy, mRNA does not insert DNA into the nucleus nor does it make a permanent change to DNA, and mRNA therapy can be dosed in a drug-like way so that the individual’s response may be managed over time. Moderna currently has several ongoing clinical trials to evaluate the safety and efficacy of mRNA as a vaccine and as cancer treatment in people.

Recently, Moderna announced that the company is developing two potential mRNA therapies for MMA and PA: (1) mRNA-3704 is an mRNA therapy to make MUT enzyme in liver as a potential treatment for MMA due to MUT deficiency, and (2) mRNA-3927 is an mRNA therapy to make PCCA and PCCB proteins, which together form the PCC enzyme, in liver as a potential treatment for PA. The evidence that helped advance mRNA-3704 (MUT) was published in the scientific journal Cell Reports, which reported the preclinical efficacy and safety of MUT mRNA therapy in MMA mice. The MMA research was conducted in collaboration with Dr. Charles P. Venditti and his colleagues at the National Human Genome Research Institute, National Institutes of Health (Bethesda, MD) under a Cooperative Research and Development Agreement (CRADA). The company also just announced in March that mRNA-3704 (MUT) has been granted Orphan Drug Designation by the FDA. Moderna is currently working to move both mRNA therapies for MMA and PA into clinical studies as soon as possible, to see if the therapeutic effects observed in mice will be seen in people with MMA or PA.

To support the advancement of these mRNA approaches, Moderna will conduct a global, observational clinical study of MMA mut and PA (MaP study) to better understand these diseases and to help identify what are the most relevant problems (clinical endpoints) that people with MMA mut and PA have to face. Information learned from the MaP study may be used in future treatment trials to see if there is an improvement due to therapy. Additionally, the data from people who participate in MaP may be used as a comparison to data from people who participate in clinical studies that are conducted to evaluate the safety and effectiveness of mRNA medicines.

In the MaP study, your doctor will work with you to collect information at 6-month intervals for up to 3 years, concomitant with your routine check-ups, so that no additional doctor visits or tests outside of routine check-ups are required. Your doctor and his/her staff will enter information into the study so that there is no additional work for participants aside from completing short quality of life questionnaires and providing a small sample of blood at each visit. The blood will be analyzed at a central laboratory to help us better understand disease biomarkers that could be used in future treatment trials. The study will additionally collect information such as frequency of metabolic decompensations and hospitalizations. 

Moderna is working with multiple sites throughout the US, UK, France, Germany, Italy, Spain and other countries to participate in MaP. If you are interested in participating in the MaP study, please contact Kathy Stagni or ask your doctor. In addition, OAA has recently started an online natural history study which is patient-driven and includes people with all organic acidemias, including MMA and PA.  We encourage your participation in their important study as well. The goal of these studies and the NIH studies is to move the field forward in gaining greater understanding of the challenges that people with organic acidemias experience and the impacts on health and quality of life. If you have MMA mut or PA, you can participate in all studies at the same time, if you choose to, in order to maximize your contribution to furthering the understanding of the course of these diseases and their impacts on people.

As a company, we are committed to leverage our unique platform to the benefit of patients with rare genetic diseases, and are inspired by the opportunity to help people with MMA and PA. We recognize and are driven by the urgent need for an effective treatment. We look forward to working with OAA as we move to quickly advance these potential medicines and to engage with and learn from the community in the months and years ahead.