From certain partnerships can emerge not only a better understanding of rare diseases but potential therapeutic options. As described by BioProcess International, a nonprofit organization called the Institute for Life Changing Medicines (ILCM) joined into a partnership recently with biotechnology and pharmaceutical company Moderna, Inc. Through this partnership, ILCM and Moderna will work to develop mRNA-3351, a potential mRNA therapy, for patients with Crigler-Najjar Syndrome Type 1 (CN-1).
Crigler-Najjar Syndrome Type 1 (CN-1)
To begin, let’s explore what Crigler-Najjar Syndrome Type 1 is. According to the Genetic and Rare Diseases Information Center (GARD), Crigler-Najjar syndrome type 1 is an inherited genetic disorder caused by UGT1A1 gene mutations. The condition is inherited in an autosomal recessive pattern, meaning patients must receive one defective copy from each parent.
Normally, bilirubin, a yellow compound that occurs during the breakdown of red blood cells, is excreted through our livers. But in patients with Crigler-Najjar syndrome type 1, patients are missing a specific enzyme. This enzyme typically takes bilirubin and makes it so that our body can easily remove it. But when this enzyme is missing or deficient, bilirubin cannot be taken out of the body, causing health issues.
There is also another form of Crigler-Najjar syndrome (type 2), though this is less severe. In patients with type 1, bilirubin accumulates throughout the body, causing a variety of health issues and organ damage. Without treatment, Crigler-Najjar syndrome type 1 can be fatal in childhood. Despite its rare status, with only around 70-100 cases worldwide, Crigler-Najjar syndrome seems to disproportionately affect Amish and Mennonite communities, which account for around 20% of all diagnoses.
Symptoms
Symptoms include:
- Kernicterus (brain damage caused by bilirubin buildup in brain and nerves)
- Jaundice (yellowing of the skin and eyes)
- Fatigue
- Abdominal pain
- Difficulty swallowing
- Nausea and vomiting
- Decreased muscle tone
- Diarrhea
- Fever
- Slurred speech
- Changes in gait and/or frequent falling
- Choreoathetosis (involuntary writhing)
- Seizures
- Brain, muscle, and nerve damage
In terms of treatments, there are some available. For example, patients require regular phototherapy, blood transfusions, and calcium compounds. In more severe cases, patients may require liver transplantation.
mRNA-3351
Because current treatments may be invasive and time-consuming, new therapies are needed. Thus, this partnership has the potential to fill an unmet need within this patient population. In a news release to company investors, Moderna explains that:
mRNA-3351 encodes for the human UGT1A1 and is designed to restore the missing or dysfunctional proteins that causes [CN-1].
To develop this, Moderna utilized similar lipid nanoparticle (LNP) technology as it had in the past. For example, Moderna also utilized LNP to develop a chikungunya vaccination. Now, within this partnership, Moderna is licensing mRNA-3351 to ILCM for free. In return, ILCM will spearhead both clinical development and clinical trials. Altogether, the partnership hopes to begin studying the treatment in clinical trials as soon as the beginning of next year.
From the FDA, mRNA-3351 received Rare Pediatric Disease designation. This designation is granted to drugs or biologics intending to treat pediatric patients (under 18) with rare or chronic conditions (affecting under 200,000 Americans).
