The term “peroxin drug” does not refer to a single, specific medication you can get from a pharmacy. Instead, it describes a class of drugs that are currently under investigation for their ability to target proteins called peroxins. These proteins are fundamental to the proper functioning of peroxisomes, which are specialized compartments within our cells. Peroxisomes perform a variety of metabolic jobs, and the drugs being developed aim to correct issues that arise when these compartments fail to work correctly due to faulty peroxins. This field of research is focused on addressing the root cause of certain genetic diseases.
The Role of Peroxins in Cellular Health
Every human cell contains peroxisomes, which act as cellular recycling and processing centers. These organelles are responsible for a range of metabolic functions, including the breakdown of very long-chain fatty acids for energy and the neutralization of harmful reactive oxygen species. They are enclosed by a single membrane and contain a dense core of enzymes that carry out these chemical reactions. Without functional peroxisomes, toxic substances can accumulate, leading to cellular damage.
The formation and maintenance of these peroxisomes are managed by a group of proteins known as peroxins, or PEX proteins. Peroxins are responsible for the entire life cycle of a peroxisome, from its creation to its ability to import necessary enzymes. Think of peroxins as the dedicated construction and maintenance crew for the peroxisome factory. They assemble the structure, ensure it is supplied with the right machinery, and oversee its operations to keep the cell healthy.
Different PEX proteins have highly specialized jobs in this process. For instance, some peroxins are located on the peroxisome’s membrane and are responsible for recognizing and importing the specific enzymes that need to be inside. Other peroxins are involved in the division of existing peroxisomes to create new ones as the cell grows and divides. This coordinated action ensures that every cell has an adequate supply of fully functional peroxisomes to manage its metabolic needs.
Peroxisomal Disorders
When the genes that provide instructions for making peroxin proteins contain mutations, the resulting proteins can be faulty or absent. This leads to a group of rare and severe genetic conditions known as peroxisomal disorders (PBDs). The severity of the disease often depends on the nature of the mutation and how much it impacts peroxin function.
The most well-known group of these conditions is the Zellweger syndrome spectrum, which includes a range of disorders from the most severe Zellweger syndrome to the milder neonatal adrenoleukodystrophy and infantile Refsum disease. Because peroxisomes are present in cells throughout the body, their dysfunction has widespread consequences. Patients often experience significant health problems affecting the brain, liver, and kidneys. Neurological issues can include developmental delays, seizures, and hearing and vision loss.
The accumulation of substances that peroxisomes normally break down, such as very long-chain fatty acids, is a hallmark of these disorders. These fatty acids can build up in tissues and cause damage, particularly to the myelin sheath that insulates nerve cells, which contributes to the neurological symptoms seen in patients. The diagnosis is often confirmed through genetic testing and by measuring the levels of these specific substances in the blood. Currently, treatments for PBDs are primarily supportive and focus on managing symptoms.
Developing Drugs Targeting Peroxins
Research into treatments for peroxisomal disorders is focused on developing therapies that can correct the underlying problems caused by faulty PEX proteins. Several strategies are being investigated:
- Pharmacological chaperones are small molecule drugs designed to bind to misfolded peroxin proteins and help them fold into a more stable, functional shape. This approach could potentially restore enough protein function to improve the assembly and operation of peroxisomes.
- Gene therapy aims to deliver a correct copy of the faulty PEX gene to the patient’s cells. For example, elivaldogene autotemcel is a gene therapy that adds functional copies of the ABCD1 gene into a patient’s own stem cells to produce a protein needed for peroxisomal function. This one-time treatment has been developed to slow the progression of a related disorder, cerebral adrenoleukodystrophy.
- Researchers are also investigating compounds that can induce the production of more peroxisomes, which may help compensate for reduced function. For instance, sodium 4-phenylbutyrate has been shown in laboratory studies to increase the number of peroxisomes in cells from patients with milder forms of PBDs.
- For certain types of mutations, scientists are exploring read-through compounds that can enable the cell’s machinery to ignore the mutation and produce a full-length, functional protein.
While these approaches are still largely in the experimental stage, they represent a shift from purely symptomatic care to therapies that target the molecular basis of the disease.