Some promising candidates for future drug therapies are small molecules that take advantage of specific biochemical pathways and interfering RNAs (RNAi) that reduce the toxic level of certain individual proteins.

Small Molecules

Through clarifying the processes that underlie several forms of brain damage, the potential to use small molecule drugs that alter these processes opens up. In developing animal models using approaches based on known mechanisms of drugs, some recent success has been achieved. Some examples include drugs such as several antibiotics and anti-tumor drugs, which appear to reduce neuronal damage in amyotrophic lateral sclerosis (ALS), Huntington’s disease and Parkinson’s disease.

Thousands of small molecule drug candidates can be tested using high throughput screening to alter a cellular property that represents an important part of the disease process. Since many neurodegenerative diseases are involve proteins that fold wrong and clump abnormally, lasers are used to measure whether proteins are clumped abnormally in the cells that have been robotically distributed into tiny wells, along with the small molecules to be tested.

Then, a machine scans the wells and reports whether the small molecules have been able to alter the protein clumping. If so, those particular small molecules can be further tested as potential therapeutic drugs. Using this method, new leads for drugs against Alzheimer’s disease and prion disease have recently been described.

RNA interference

Several neurodegenerative diseases are caused by the accumulation of abnormal proteins. So, if the cells in the body made less of such proteins to begin with, the disease would progress much more slowly. A new class of potential therapeutic drugs is based on removing the RNAs that code for the proteins that are causing damage. Mouse models of Huntington’s disease and ALS appear to have responded positively to such treatment, which are delivered via gene therapies.

Through RNA interference, it can be controlled which genes are active and how active they are. RNA molecules are the direct products of genes and two types of RNA (microRNA or miRNA, and small interfering RNA or siRNA) can bind to specific other RNAs and either increase or decrease their activity, for example by preventing a messenger RNA from producing a protein. Naturally, such interference has an important role in defending the cells against parasitic genes and in directing development and gene expression. They can also, however, be used as therapeutic drugs, silencing the expression of the genes that code for the disease causing proteins.

Sources

• Bagasra O, Prilliman KR (2004). "RNA interference: the molecular immune system". J. Mol. Histol. 35 (6): 545–53.
• Brain Facts: A Primer on the Brain and Nervous System. Society for Neuroscience.