Introduction: Monogenic neurological disorders are those that are caused by a mutation in a single gene, such as spinal muscular atrophy (SMA), Huntington's disease, and some rare epilepsies. They often manifest in childhood and can cause severe disability. Until recently, treatment was only directed at controlling symptoms like seizures or motor dysfunction. However, developments in biotechnology and genetics have now made it possible to develop targeted therapies that attempt to repair or counteract the effects of the faulty gene itself. This essay outlines some of the major strategies being investigated.
Methods: For this review, recent studies and reviews published between 2018 and 2025 were considered, utilizing databases such as PubMed and Scopus. Keywords included “monogenic neurological disorders,” “gene therapy,” and “antisense oligonucleotides.” The focus was on new treatments that directly target the genetic cause of disease, rather than only relieving symptoms.
Results: 1. Antisense Oligonucleotides (ASOs):
ASOs are small DNA-like compounds that can alter the way cells interpret RNA. One success is nusinersen, which is applied in SMA and serves to restore the missing SMN protein. The same ASOs are in trials for Huntington's disease and genetic migraine.
2. Gene Replacement Therapy:
It uses harmless viruses, such as adeno-associated viruses (AAVs), to insert healthy copies of genes into nerve cells. Onasemnogene abeparvovec, for SMA, is an excellent example. Scientists are now trying this approach for Rett syndrome and other rare diseases.
3. Genome Editing (CRISPR):
CRISPR-CAS systems allow mutations to be repaired directly. Still mainly in research, but already successful in animal models of muscular dystrophy and epilepsy. Improvements like base editing are being made to reduce errors.
4. RNA Interference (RNAi):
It uses small RNAs to "silence" harmful genes. Already approved for some non-brain diseases, researchers are testing it in Huntington's disease to lower levels of toxic protein.
5. New Delivery Strategies:
A major challenge is how to deliver these therapies safely into the brain. Progress is being made with viruses engineered for this purpose, as well as nanoparticles and other delivery vehicles that can cross the blood–brain barrier.
Conclusion: Targeted therapies for monogenic neurologic disorders are quickly moving from the laboratory bench to real therapies. ASOs and gene replacement have already transformed therapy for SMA, and others like CRISPR and RNAi are on the horizon. Sure, there remain issues—chiefly safety, delivery, and expense—but these approaches bring new hope that genetic disorders once deemed untreatable perhaps may someday be treatable, even curable.