Chapter 15: Potential Therapies

In this Chapter…

Most medications today are developed using trial-and-error
The potency of the agent can be determined by how well it attaches to the receptor/protein target in a test tube
Candidates for new neurological drugs include * trophic factors * antibodies engineered to modify the interactions and toxicity of misfolded proteins * $RNAi:$ interfering RNAs * They could reduce the toxic levels of individual proteins * Stem cells * They could replace dead or dying neurons

Trophic factors control the development and survival of specific groups of neurons
Once specific actions of these molecules and their receptors are identified, their genes can be cloned * Procedures can be developed to modify trophic factor-regulated functions in ways that might be useful in the treatment of neurological disorders
$NGF (Nerve Growth Factor)$ : a trophic factor that slows the destruction of neurons that use acetylcholine * A possible treatment * Prevented cell death & stimulated regeneration & sprouting of damaged neurons that are known to die in Alzheimer’s disease * Holds promise for slowing memory deficits associated with aging
Neutralizing molecules that stop or inhibit growth can help repair damaged nerve fiber tracts in the spinal cord * Antibodies that override the effect of Nogo-A helped some nerves of damaged spinal cords to regrow * $Nogo-A$ : a protein that inhibits nerve regeneration

We can “trick” the immune system into attacking proteins that cause neurological disease by vaccinating against them * There’s a risk of increased inflammation when the brain reacts to antibodies against its proteins
A new approach is to engineer fragments of antibodies that can bind to and alter disease characteristics of specific proteins * These have produced promising results for Huntington’s, Parkinson’s, Alzheimer’s, and prion diseases
Fruit flies that have been modified to carry a mutant gene for Huntington’s are generally too weak & uncoordinated to break out of their pupal case * When treated to also express a gene for anti-HD antibodies, all emerge as young adults * Treated flies live longer than untreated ones that manage to emerge and show less pathology in their brains

Small-molecule drug candidates can be tested using high-throughput screening
Many neurological diseases involve denatured proteins
Lasers are used to measure whether proteins are clumped inside cells that have been distributed into containers with small molecules * They scan containers and report whether particular drugs have changed protein clumping
Many diseases also involve the accumulation of abnormal proteins * If cells made fewer such proteins, the disease would slow down
A new class of drugs involves removing the RNAs that code for these proteins

$Neuronal stem cells$ - unspecialized cells that give rise to cells with specific functions
Neuronal stem cells can continuously produce all 3 cell types present in the brain: * Neurons * $Astrocytes$ - glial cells that protect and nourish neurons * $Oligodendrocytes$ - glial cells that surround axons and make the myelin sheath
Viruses may be able to carry therapeutic genes into the brain to correct central nervous system diseases

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