Pelizaeus-Merzbacher disease (PMD) is a progressive central nervous system disorder that primarily affects oligodendrocytes (the cells responsible for producing myelin). In many cases of PMD, a duplication of the PLP1PLP1PLP1 gene leads to an overproduction of the proteolipid protein 1 (PLP1). This excess protein is toxic to oligodendrocytes, causing them to die and leading to severe demyelination in the brain and spinal cord.
A clinical trial is evaluating a new treatment for PMD using an antisense oligonucleotide (ASO). This drug consists of a short, single-stranded DNA molecule designed to target the PLP1PLP1PLP1 gene transcript. The drug is administered via intrathecal injection (directly into the cerebrospinal fluid surrounding the spinal cord).
Answer the following questions based on this information:
Explain how the loss of the myelin sheath around axons in the central nervous system leads to slower or failed transmission of nerve impulses.
Suggest and explain how this single-stranded DNA-based drug can lead to a reduction in the concentration of the toxic PLP1 protein.
Suggest two reasons why this DNA-based drug must be administered directly into the cerebrospinal fluid rather than taken orally as a pill.
