Numerous illnesses are triggered by impaired gene expression that results in an excess or deficiency of a particular protein. Initiatives aimed at remedying these illnesses encompass everything from modifying genes to integrating new genetic fragments into cells and even administering the absent proteins directly to patients.
CAMP4 is adopting an alternative strategy. The firm is focusing on a lesser-known participant in the modulation of gene expression called regulatory RNA. CAMP4 co-founder and MIT Professor Richard Young has demonstrated that through interactions with molecules known as transcription factors, regulatory RNA plays a crucial role in managing how genes are expressed. CAMP4’s treatments aim to target regulatory RNA to enhance the synthesis of proteins and restore patients’ levels to normal ranges.
The company’s strategy shows promise for addressing diseases resulting from gene expression anomalies, including metabolic disorders, cardiovascular issues, and neurological conditions. Targeting regulatory RNAs instead of genes may also present more targeted treatments in comparison to traditional methods.
“If my goal is to rectify the defective protein output of a single gene, I would prefer not to introduce something that causes that protein to be produced in excessive, uncontrolled levels,” remarks Young, who is also a key member of the Whitehead Institute. “This is a significant benefit of our method: it functions more like a correction than a blunt instrument.”
CAMP4’s primary drug candidate targets urea cycle disorders (UCDs), a category of chronic ailments stemming from a genetic flaw that restricts the body’s ability to process and eliminate ammonia. A phase 1 clinical trial indicated that CAMP4’s treatment is both safe and well-tolerated in humans, and preliminary studies have demonstrated that the company’s approach can specifically target regulatory RNA in human cells with UCDs to return gene expression to healthy levels.
“This has the potential to alleviate extremely severe symptoms linked to UCDs,” asserts Young, who co-founded CAMP4 alongside cancer genetics expert Leonard Zon, a professor at Harvard Medical School. “These conditions can severely damage tissues and induce significant pain and suffering. Even a minor improvement in gene expression could greatly benefit patients, many of whom are quite young.”
Charting new treatments
Young, who has been a faculty member at MIT since 1984, has dedicated decades to investigating the regulation of genes. It has been well-established that molecules known as transcription factors, which orchestrate gene activity, attach to DNA and proteins. Studies conducted in Young’s laboratory revealed a previously unrecognized mechanism through which transcription factors can also connect to RNA. This discovery highlighted the often-overlooked role of RNA in controlling gene expression.
CAMP4 was established in 2016 with the initial concept of charting the signaling pathways that regulate the expression of genes associated with various diseases. However, as Young’s laboratory uncovered and began to define the role of regulatory RNA in gene expression around 2020, the company shifted its focus to targeting regulatory RNA with therapeutic molecules known as antisense oligonucleotides (ASOs), which have been utilized for years to target specific mRNA sequences.
CAMP4 embarked on mapping the active regulatory RNAs linked to the expression of every protein-coding gene and developed a database, referred to as its RAP Platform, which expedites the identification of regulatory RNAs to target particular diseases and select ASOs that will effectively bind to those RNAs.
Currently, CAMP4 is leveraging its platform to create therapeutic candidates it believes can restore healthy protein levels for patients.
“The company has consistently aimed at modulating gene expression,” states CAMP4 Chief Financial Officer Kelly Gold MBA ’09. “At its most fundamental level, the core of many diseases lies in the production of too much or too little of something by the body. That is the issue our approach seeks to rectify.”
Accelerating impact
CAMP4 is commencing its efforts by focusing on liver diseases and disorders of the central nervous system, where the safety and effectiveness of ASOs have already been established. Young is convinced that correcting genetic expression without altering the genes themselves will form a robust method for treating a variety of complex diseases.
As the company persists in mapping the regulatory RNAs associated with every gene, Gold anticipates that CAMP4 can eventually decrease its dependence on laboratory work and rely more on machine learning to utilize its expanding database and swiftly identify regulatory RNA targets for each condition it aims to address.
In addition to its trials involving urea cycle disorders, the firm plans to initiate significant preclinical safety assessments for a candidate targeting seizure disorders with genetic origins within this year. As the company continues to delve into drug development initiatives surrounding the multitude of genetic disorders where enhancing protein levels can yield significant benefits, it is also contemplating partnerships with others to expedite its impact.
“I can envision enterprises using a platform like this to pursue numerous targets, where collaborators finance the clinical trials and use CAMP4 as a driving force to target any disease where there is suspicion that gene upregulation or downregulation is the solution,” Young concludes.